Prognostic Analysis of Postoperative Survival for Ruptured Hepatocellular Carcinoma with or without Cirrhosis.
Conflicting results are often observed in the prognosis of patients with ruptured hepatocellular carcinoma (rHCC), and there are currently very few studies on the long-term postoperative outcomes of ruptured hepatocellular carcinoma patients. This study aimed to distinguish between the postoperative prognosis of rHCC patients with cirrhosis (rHCC-C) and those without cirrhosis (rHCC-NC) using some serum markers. We collected the data of 151 rHCC patients treated at our centers from January 2010 to March 2021. 62 had no cirrhosis, and 89 had cirrhosis. The prognosis of rHCC-C and rHCC-NC groups was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in rHCC patients, and subgroup analysis was performed on the two groups of patients. The long-term prognosis of rHCC-NC patients was better than that of rHCC-C patients. Tumor diameter, Barcelona clinic liver cancer (BCLC) stage, HBsAg, positive Hepatitis C virus (HCV) antibodies, elevated creatinine, and elevated T-bilirubin were prognostic factors for overall survival (OS) in rHCC-C patients. However, only alpha-fetoprotein (AFP) > 92 ng/mL was a prognostic factor for OS in rHCC-NC patients. In noncirrhotic patients, HBsAg positivity was only associated with OS. Similarly, the presence or absence of microvascular invasion (MVI) also had different results in the two groups. There are differences in serum alpha-fetoprotein (AFP) levels, the presence of microvascular invasion (MVI), and HBsAg positivity between rHCC-C and rHCC-NC patients, indicating that the analysis of these prognostic factors may help improve the management of rHCC patients and provide a direction for future treatment options.


"Don't eat so much:" how parent comments relate to female weight satisfaction.
How will the words of a parent influence the adult weight of their daughter? This retrospective study evaluates how the recalled comments of parents made about the weight or eating habits of a daughter related to her adult BMI and satisfaction with her weight. A nationwide cross-sectional survey was conducted with 501 young women ranging in age from 20 to 35 (age 26.8, SD 3.1; BMI 25.96, SD 6.2), who were asked to indicate their weight satisfaction, eating habits, and BMI along with their recall of the extent to which they recalled their parents making weight-related or eating-related comments about them as a young girl. Linear regression analyses were run to examine the relationship between parental comments and women's weight satisfaction and BMI. A woman's dissatisfaction with her adult weight was only related to the extent she remembered her parents making any comments about her weight (p < 0.01), but not about how much she ate (p < 0.05)-even though both were positively related to her BMI (p < 0.001 and p < 0.01). Even among normal-weight young women with similar weights, those who recalled their parents commenting about their weight were more dissatisfied with their body weight (p < 0.01). In this retrospective study, a parent's comments about her childhood weight were related to her weight and body dissatisfaction as an adult. In contrast, comments about her eating habits were not significantly related to weight dissatisfaction.


DeepMHCI: an anchor position-aware deep interaction model for accurate MHC-I peptide binding affinity prediction.
Computationally predicting major histocompatibility complex class I (MHC-I) peptide binding affinity is an important problem in immunological bioinformatics, which is also crucial for the identification of neoantigens for personalized therapeutic cancer vaccines. Recent cutting-edge deep learning-based methods for this problem cannot achieve satisfactory performance, especially for non-9-mer peptides. This is because such methods generate the input by simply concatenating the two given sequences: a peptide and (the pseudo sequence of) an MHC class I molecule, which cannot precisely capture the anchor positions of the MHC binding motif for the peptides with variable lengths. We thus developed an anchor position-aware and high-performance deep model, DeepMHCI, with a position-wise gated layer and a residual binding interaction convolution layer. This allows the model to control the information flow in peptides to be aware of anchor positions and model the interactions between peptides and the MHC pseudo (binding) sequence directly with multiple convolutional kernels. The performance of DeepMHCI has been thoroughly validated by extensive experiments on four benchmark datasets under various settings, such as 5-fold cross-validation, validation with the independent testing set, external HPV vaccine identification, and external CD8+ epitope identification. Experimental results with visualization of binding motifs demonstrate that DeepMHCI outperformed all competing methods, especially on non-9-mer peptides binding prediction. DeepMHCI is publicly available at https://github.com/ZhuLab-Fudan/DeepMHCI.


Effect of preconditioning by light load eccentric exercise versus heat on markers of muscle damage in collegiate males.
Delayed onset muscle soreness (DOMS) occurs following unaccustomed or intense bouts of exercise. Previous research has demonstrated that that preconditioning with low load exercise or heat relieves muscle soreness. However, actively warming up the muscles with exercise may be an effective alternative. This study compared preconditioning effect of light load eccentric exercise and heat using microwave diathermy on markers of muscle damage in collegiate males. Thirty six sedentary collegiate males were randomly assigned into two experimental groups: 10% Eccentric exercise group (10% ECC group) and Microwave diathermy group (MWD group). Both the groups performed 30 repetitions of maximal eccentric exercise (Max-ECC) of the elbow flexors. The 10% ECC group performed light load eccentric exercise (10% ECC), five sets, six repetitions using a dumbbell set at 10% of maximal voluntary isometric contraction strength (MVC), 2 days prior to Max-ECC. The MWD group received heat using microwave diathermy (150 watts, 20 minutes) one day prior to Max-ECC. Changes in MVC, range of motion (ROM), upper arm circumference, soreness, were assessed before and 24-72 hours after whereas serum creatine kinase activity and lactate dehydrogenase (LDH) activity up to 48 hours following the Max-ECC were compared between groups by a mixed model ANOVA. No significant difference (P > 0.05) were found between the groups for changes in all variables post Max-ECC, except for LDH activity showing significant interaction effect (P = 0.04). Preconditioning with light load eccentric exercise and heat using microwave diathermy treatment did not differ in their effects on muscle damage markers after Max-ECC. However, with time their effects on LDH activity were found to be different.


Evaluation of Intra Root Canal Er,Cr:YSGG Laser Irradiation on Prosthetic Post Adherence.
In clinical prosthetics procedures, including endodontics and post fixation, the presence of a smear layer can reduce the post bond strength. An Er,Cr:YSGG laser, which emits at 2780 nm, can promote a smear-layer-free surface due to the ablation process. Considering these aspects, the purpose of this work was to evaluate the influence of Er,Cr:YSGG laser irradiation using either a radial or an axial fiber tip on the bond strength of three resin cements to the fiber-reinforced composite posts. Ninety recently extracted single rooted human teeth had their root canal instrumented and were randomly distributed into nine experimental groups, in which three resin cements (total-etching Variolink II, self-etching Panavia F, and self-adhesive RelyX Unicem Aplicap) and three root canal treatments (no treatment, laser irradiation using the radial fiber tip, laser irradiation using the axial fiber tip) were used. Specimens were then sectioned into three sections (cervical, middle, and apical thirds) with two slices on each section. A push-out test was performed on each slice, and the values were recorded as MPa. The push-out data were analyzed by a Ryan-Joiner normality test followed by a two-way ANOVA test and Tukey pairwise comparison. The statistical analysis was performed on each third section separately, with a 5% significance level. Laser irradiation with axial fiber tip significantly increased the post bond strength of RelyX Unicem Aplicap on middle third of specimens (p < 0.001) when compared to other root canal treatments (unlased or irradiated with radial tip). Considering the Panavia resin cement, laser irradiation with either axial or radial tips promoted a significant increase on the post bond strength of middle third when compared to unlased specimens (p < 0.001); however, laser irradiation did not influence the post bond strength of Variolink resin cement. The use of the Er,Cr:YSGG laser for clinical prosthetics procedures enhances the post bond strength of Panavia and RelyX Unicem Aplicap resin cements, mainly at middle third of roots, and does not interfere with the bond strength of Variolink resin cement. For the RelyX Unicem Aplicap system, the use of axial tip is most advantageous and can be recommended for future clinical application.


Treatment of recurrent symptomatic ventricular tachycardia.
Eleven consecutive patients with recurrent ventricular arrhythmias were treated by an aggressive protocol and followed up prospectively. Arrhythmias, symptoms, and cardiac lesions were defined. Antiarrhythmic drugs were given on schedule, with blood levels determining dose; success or failure was defined by elimination or recurrence of symptomatic arrhythmias. When drug therapy failed, left ventricular aneurysmectomy was done when appropriate. Recurrent ventricular tachycardia was most frequently responsible for symptoms; coronary artery disease was the most frequent underlying disease. Symptomatic arrhythmias were eliminated in 8 of 11 patients (5 with drugs and 3 with aneurysmectomies), with a 16.5-month symptom-free average follow-up. An average of 2.9 therapeutic trials per patient was needed to control symptomatic arrhythmias. The average time from entry into the study until the start of ultimately effective therapy was 18 days. Therapy that eliminated symptoms did not eliminate all premature ventricular contractions, and occasionally even brief asymptomatic episodes of ventricular tachycardia persisted. Recurrent symptomatic ventricular arrhythmias can be controlled in many patients by rigorous application of current therapies.


Paliperidone palmitate: Japanese postmarketing mortality results in patients with schizophrenia.
Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population. All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed. During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person-years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy. Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes.


In search of behavioral and brain processes involved in honey bee dance communication.
Honey bees represent an iconic model animal for studying the underlying mechanisms affecting advanced sensory and cognitive abilities during communication among colony mates. After von Frisch discovered the functional value of the waggle dance, this complex motor pattern led ethologists and neuroscientists to study its neural mechanism, behavioral significance, and implications for a collective organization. Recent studies have revealed some of the mechanisms involved in this symbolic form of communication by using conventional behavioral and pharmacological assays, neurobiological studies, comprehensive molecular and connectome analyses, and computational models. This review summarizes several critical behavioral and brain processes and mechanisms involved in waggle dance communication. We focus on the role of neuromodulators in the dancer and the recruited follower, the interneurons and their related processing in the first mechano-processing, and the computational navigation centers of insect brains.


Tritiated starch granules.
1. Surface-labelling of starch granules by tritiation seems feasible, and a technique is described that could be useful in structure determination. The impurities that are produced must be taken into account but the fact that a high polymer can be successfully tritiated seems very promising. 2. The surfaces of corn-starch granules must contain both amylose and amylopectin.


Development and validation of an automatic treatment referral system.
The alcoholism literature abounds with reports of the alcoholic personality and alcoholic subtypes. However, very minimal research on the relationship between the subtypes and treatment procedures is available. With the power of computer technology now accessible so readily, it is possible to apply sophisticated statistical methods to determine the extent of the association. The present paper describes the development of an automatic referral system (Autorf) on an inpatient alcohol and day unit (N = 150). More importantly, preliminary results with regard to the validity of the Autorf system are reported. Implications for treatment of alcoholics and program efficiency are discussed.


Species Classification for Neuroscience Literature Based on Span of Interest Using Sequence-to-Sequence Learning Model.
Large-scale neuroscience literature call for effective methods to mine the knowledge from species perspective to link the brain and neuroscience communities, neurorobotics, computing devices, and AI research communities. Structured knowledge can motivate researchers to better understand the functionality and structure of the brain and link the related resources and components. However, the abstracts of massive scientific works do not explicitly mention the species. Therefore, in addition to dictionary-based methods, we need to mine species using cognitive computing models that are more like the human reading process, and these methods can take advantage of the rich information in the literature. We also enable the model to automatically distinguish whether the mentioned species is the main research subject. Distinguishing the two situations can generate value at different levels of knowledge management. We propose SpecExplorer project which is used to explore the knowledge associations of different species for brain and neuroscience. This project frees humans from the tedious task of classifying neuroscience literature by species. Species classification task belongs to the multi-label classification which is more complex than the single-label classification due to the correlation between labels. To resolve this problem, we present the sequence-to-sequence classification framework to adaptively assign multiple species to the literature. To model the structure information of documents, we propose the hierarchical attentive decoding (HAD) to extract span of interest (SOI) for predicting each species. We create three datasets from PubMed and PMC corpora. We present two versions of annotation criteria (mention-based annotation and semantic-based annotation) for species research. Experiments demonstrate that our approach achieves improvements in the final results. Finally, we perform species-based analysis of brain diseases, brain cognitive functions, and proteins related to the hippocampus and provide potential research directions for certain species.


Flow cytometric CD34+ determination in stem cell transplantation: before or after cryopreservation of grafts?
Various attempts have been made to standardize and improve the reproducibility of flow cytometric determination of CD34+ hematopoietic progenitor cells. It is still not clear, however, whether the quantification of CD34+ cells in a stem cell graft should be done before or after cryopreservation. To address this issue, we investigated 78 unselected and 32 immunomagnetically selected autologous and allogeneic leukapheresis products (LA) before and after cryopreservation using pilot vials. Cell numbers were quantified within a Neubauer chamber, and CD34+ content was determined by flow cytometry; propidium iodide staining was used to exclude dead cells from analysis. Before freezing, the mean viable CD34 cell content in the unselected samples was 1.22% and increased after thawing to a mean of 2.16% of viable cells. Taking into account cell loss and cell death, the overall recovery of viable cells was 64.5%; all CD34+ cells could be recovered. Mean purity in the CD34-selected cell fraction was 85% (48-97) before and 91.3% (67-99) after thawing. The number of viable cells was 86.8% before and 86.1% after freezing with a 93.9% recovery of total cells. This leads to a mean 93.7% (SD +/- 23.1) recovery of viable cells and 100% (SD +/- 22.3) recovery of viable CD34+ cells. There was no significant difference in tolerance to freeze/thaw stress between cells from heavily pretreated autologous patients and healthy allogeneic donors. Our data show that freezing significantly increases the percentage of CD34(+) cells in unmanipulated LA, probably due to the death of granulocytes and mononuclear cells (MNCs). Nevertheless, the overall number of viable CD34+ cells in unselected as well as selected samples remains unchanged. Thus, CD34 data from different laboratories, for example, within multicenter trials, should be comparable independent of the different time points of acquisition.


Differential activation of cysteine-substitution mutants of fibroblast growth factor receptor 3 is determined by cysteine localization.
Various human skeletal disorders are thought to be caused by mutations in fibroblast growth factor receptor 3 (FGFR3). These result in chronic FGFR3 hyperactivation and inhibition of bone growth. One such disorder, thanatophoric dysplasia, the most common form of sporadic, lethal dwarfism, is associated frequently with cysteine substitutions (G370C, S371C, and Y373C) in the extracellular juxtamembrane region of the receptor. These mutations have been suggested to induce disulfide-mediated receptor dimerization and constitutive activation. An adjacent cysteine substitution (G375C) leads to a less severe form of human dwarfism, achondroplasia, suggesting that the intensity of FGFR3 activation by these cross-links may be position dependent. To test this hypothesis, we have sequentially replaced each amino acid at positions 370-375 of FGFR3 with cysteine. Expression of each of these mutant forms in 293T cells led to their spontaneous, ligand-independent dimerization and increased basal phosphorylation. Wild-type (WT) FGFR3 became dimerized and phosphorylated only on FGF stimulation. Among the mutants, only two (G370C and S371C) caused high basal phosphorylation with significantly increased constitutive levels of mitogen-activated protein kinase (MAPK) phosphorylation and c-fos transcription. This activity was probably caused by mutant homodimer pairs, because WT-mutant heterodimers were observed only in the presence, but not in the absence, of FGF1. The high spontaneous activity of the mutants in positions 370-371, unlike those in 372-375, affirms their known involvement with thanatophoric dysplasia. We conclude that the G370C and S371C mutant receptors spontaneously dimerize in the correct spatial orientation required for effective signal transduction, whereas the 372-5 mutants, like the WT receptor, may achieve this orientation only on ligand binding.


Na adsorption on the Si111-(7 x 7) surface: from two-dimensional gas to nanocluster array.
We have systematically investigated Na adsorption on the Si(111)-(7 x 7) surface at room temperature using scanning tunneling microscopy (STM). Below the critical coverage of 0.08 monolayer, we find intriguing contrast modulation instead of localized Na adsorbates, coupled with streaky noise in the STM images, which is accompanied by monotonic work function drop. Above the critical coverage, Na clusters emerge and form a self-assembled array. Combined with first-principles theoretical simulations, we conclude that the Na atoms on the (7 x 7) surface are, while strongly bound ( approximately 2.2 eV) to the surface, highly mobile in "basins" around the Si rest atoms, forming a two-dimensional gas phase at the initial coverage, and that the cluster at the higher coverage consists of six Na atoms together with three Si adatoms.


PTTG/securin activates expression of p53 and modulates its function.
Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed abundantly in most tumors. Overexpression of PTTG induces cellular transformation and promotes tumor formation in nude mice. PTTG has been implicated in various cellular processes including sister chromatid separation during cell division as well as induction of apoptosis through p53-dependent and p53-independent mechanisms. The relationship between PTTG and p53 remains unclear, however. Here we report the effects of overexpression of PTTG on the expression and function of p53. Our results indicate that overexpression of PTTG regulates the expression of the p53 gene at both the transcriptional and translational levels and that this ability of PTTG to activate the expression of p53 gene is dependent upon the p53 status of the cell. Deletion analysis of the p53 gene promoter revealed that only a small region of the p53 gene promoter is required for its activation by PTTG and further indicated that the activation of p53 gene by PTTG is an indirect effect that is mediated through the regulation of the expression of c-myc, which then interacts with the p53 gene promoter. Our results also indicate that overexpression of PTTG stimulates expression of the Bax gene, one of the known downstream targets of p53, and induces apoptosis in a human embryonic kidney cell line (HEK293). This stimulation of bax expression by PTTG is indirect and is mediated through modulation of p53 gene expression. Overexpression of PTTG activates the expression of p53 and modulates its function, with this action of PTTG being mediated through the regulation of c-myc expression. PTTG also up-regulates the activity of the bax promoter and increases the expression of bax through modulation of p53 expression.


Methyl aminolevulinate (Metvix) photodynamic therapy - practical pearls.
Topical photodynamic therapy (PDT) is an effective treatment for certain non-melanoma skin cancers (NMSCs), including superficial and nodular basal cell carcinomas (sBCC and nBCC), actinic keratosis (AK) and Bowen's disease. Methyl aminolevulinate (MAL, Metvix) is licensed in Europe for use in PDT for sBCC, nBCC and thin or non-hyperkeratotic and non-pigmented AK on the face and scalp, where other therapies are unsuitable. Optimal PDT response can be achieved through appropriate patient selection and lesion preparation. Evidence of efficacy is reviewed from guidelines and clinical experience. Red light from an LED source offers a relatively efficient method of activating the photodynamic reaction. The most common side effect of PDT is pain, burning or stinging discomfort at the site of treatment, although most patients do not request pain relief. The incidental observation of surface fluorescence three hours after photosensitizer application can be utilized for tumour detection as well as delineation. Topical PDT using Metvix MAL offers a practical non-invasive therapy option with the potential for high efficacy and good cosmesis.


Purposes and models of diagnostic systems.
Emerging efforts at developing new international classification and diagnostic systems require a careful and fresh review and conceptualization of the meanings, purposes and models of diagnostic systems. Such meanings include both an informative statement as well as a process or activity. The purposes of diagnostic systems can be clustered under understanding of a case and planning effective clinical care and public health interventions. The models designed to give form to a diagnostic system must pay attention to the informational domains to be covered (from illness to positive health), the descriptive or measurement tools to be utilized (categories, dimensions, narratives), the evaluators to be engaged (clinicians, patient, family) and the structural schemas (single- or multilevel) required to accommodate meanings and purposes of interest.


Development of knowledge of visual-tactual affordances of substance.
Infants of 12 months were familiarized in the dark with an object of either a hard or an elastic (spongy) substance. Following 60 sec of manipulation, a visual preference test was given with simultaneous presentation of 2 films of identical objects, 1 moving in a pattern characteristic of a rigid object and 1 moving in a pattern characteristic of an elastic object. Infants handled the 2 substances differently in an appropriate manner and looked preferentially with more and longer first looks to the type of substance familiarized. A replication of this experiment with familiarization in the light yielded comparable results. A third experiment with 1-month-old infants allowed them to mouth objects of either a hard or a soft substance for haptic familiarization and then tested looking preferences with real objects moving rigidly or deforming. These infants looked longer at the object moving in a manner characteristic of the novel substance. The results, together, suggest that quite young infants detect intermodal invariants specifying some substances and perceive the affordance of the substance.


2019 Chitranjan S. Ranawat Award: Elective joint arthroplasty outcomes improve in malnourished patients with nutritional intervention: a prospective population analysis demonstrates a modifiable risk factor.
To date, no study has demonstrated an improvement in postoperative outcomes following elective joint arthroplasty with a focus on nutritional intervention for patients with preoperative hypoalbuminaemia. In this prospective study, we evaluated differences in the hospital length of stay (LOS), rate of re-admission, and total patient charges for a malnourished patient study population who received a specific nutrition protocol before surgery. An analytical report was extracted from the electronic medical record (EMR; Epic, Verona, Wisconsin) of a five-hospital network joint arthroplasty patient data set between 2014 and 2017. A total of 4733 patients underwent joint arthroplasty and had preoperative measurement of albumin levels: 2220 at four hospitals and 2513 at the study hospital. Albumin ≤ 3.4 g/l, designated as malnutrition, was found in 543 patients (11.5%). A nutritional intervention programme focusing on a high-protein, anti-inflammatory diet was initiated in January 2017 at one study hospital. Hospital LOS, re-admission rate, and 90-day charges were compared for differential change between patients in study and control hospitals for all elective hip and knee arthroplasty patients, and for malnourished patients over time as the nutrition intervention was implemented. Malnourished patients with nutritional intervention at the study hospital had shorter hospital LOS beginning in 2017 than malnourished patients at control hospitals during the same period (p = 0.04). Similarly, this cohort had significantly lower primary hospitalization charges, charges associated with hospital re-admissions, and 90-day total charges (p < 0.001). Inclusion of covariant potential confounders (age, anaemia, diabetes, and obesity) did not alter the conclusions of the primary statistical analysis. Joint arthroplasty outcomes were positively affected in study patients with low albumin when a high-protein, anti-inflammatory diet was encouraged. Elective surgery was neither cancelled nor delayed with a malnutrition designation. While the entire network population experienced improved postoperative outcomes, malnourished control patients did not experience this improvement. This study demonstrated that education on malnutrition can benefit patients. Cite this article: Bone Joint J 2019;101-B(7 Supple C):17-21.


[Risk factor calculator for medical underwriting of life insurers based on the PROCAM study].
For its electronic manual GEM, used to perform medical risk assessment in life insurance, SCOR Global Life Germany has developed an innovative and evidence-based calculator of the mortality risk depending on cardiovascular risk factors. The calculator contains several new findings regarding medical underwriting, which were gained from the analysis of the PROCAM (Prospective Cardiovascular Münster) study. For instance, in the overall consideration of all risk factors of a medically examined applicant, BMI is not an independent risk factor. Further, given sufficient information, the total extra mortality of a person no longer results from adding up the ratings for the single risk factors. In fact, this new approach of risk assessment considers the interdependencies between the different risk factors. The new calculator is expected to improve risk selection and standard acceptances will probably increase.


In-Situ Synthesis and High-Efficiency Photocatalytic Performance of Cu(I)/Cu(II) Inorganic Coordination Polymer Quantum Sheets.
Two-dimensional (2D) materials ultrathin quantum sheets have the advantage of elevating the catalysis performance and prominent edge effects, but most of them belong to element single valence materials. In this paper, the ultrathin Cu(I)/Cu(II) inorganic coordination polymer quantum sheet (ICPQS) {[CuII(H2O)4][CuI4(CN)6]} n is synthesized by controlling the appropriate molar ratio of raw material, reaction time, and temperature. Transmission electron microscopy (TEM) and atomic force microscope (AFM) analysis show that this ICPQS has a thickness of ∼0.2 nm. Due to the fact that about 58.16% of the Cu(I)/Cu(II) is occupied in molecular structure and most of the metal active sites are fully utilized, this ICPQS can accelerate the photocatalytic degradation of methylene blue (MB) (K = 2.5 mg·L-1·min-1 at pH 3) and organic compounds in coking wastewater and biotreated coking wastewater. Basing on mixed valences, the ICPQS can use visible light to promote energy transfer and increase quantum efficiency, paving the way for developing the next-generation monolayer 2D mixed valence photocatalysts.


Intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus in immunocompetent mice.
Critically ill surgery patients are susceptible to pulmonary reactivation of latent cytomegalovirus (CMV), but what triggers this reactivation is unknown. Immunosuppression and bacterial sepsis are thought to stimulate reactivation of CMV, and in this study it was hypothesized that immunosuppressive effects of surgery with or without concomitant bacterial infection may reactivate latent CMV. Mice infected with CMV were allowed to develop latent infections. Latently infected mice underwent a laparotomy with cecal ligation and puncture (CLP; n=30), a laparotomy alone (sham; n=10), or no surgery (control; n=5). Lung tissue homogenates were evaluated for viral activity, and, 2 and 3 weeks after CLP, lungs of 7 of 7 and 5 of 5 mice, respectively, showed reactivation of latent CMV. In contrast, lungs from all sham-operated animals and controls showed no viral reactivation. These findings demonstrate that surgery with subsequent intra-abdominal bacterial infection reactivated CMV in lungs of latently infected mice. The mechanism of this reactivation is unknown but likely involves cytokines induced by sepsis.


Detection of past and recurrent marijuana use by a modified GC/MS procedure.
A published gas chromatography/mass spectrometry method for detecting 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in urine was modified. In the new procedure, five GC/MS ion peaks of a pentafluoropropylpentafluoropropionyl derivative of THC-COOH are monitored in the multiple-ion mode for improved reliability; two ion peaks of the trideuterated internal standard are used for greater quantitative precision; and methanolic KOH is employed instead of NaOH in the hydrolysis and extraction steps to produce a cleaner extract. Finally, the new procedure is designed to keep THC-COOH either in basic solution or in an organic solvent at all times to prevent adsorption onto glass or plastic, so that disposable, non-silanized glassware may be used. Patient urines were analyzed by both the new procedure and the EMIT method. For 32 specimens, the average and range of EMIT/GC/MS concentration ratios were 2.8 and 0.9-7.2, respectively. Concentrations of THC-COOH measured by the GC/MS procedure may be more indicative of recent marijuana use than the EMIT semi-quantitative concentration values.


Anatomical and Radiologic Evaluation of the Dimensions of Upper Molar Alveoli.
The aim of the present study was to analyze the alveolar bone morphology of the upper first and second molars. This analysis aims to evaluate the morphology of a hypothetical postextractive site in the upper molar area to diagnose the possibility of immediate postextraction implant placement. Cone-beam CT scans of 100 patients were examined. The measurements were made using a dedicated 3D software. Reference points were identified to allow clear and repeatable measurements. The mean available height was 7.43 ± 3.40 mm for the upper first molars and 7.07 ± 3.09 mm for the upper second molars. The interradicular septum was present in first molars in 74% of cases and 44% of cases in upper second molars. In most cases, the alveolar sites of the upper first and second molars do not present ideal conditions for immediate implant insertion in a correct position. The primary stabilization of a standard-sized dental implant is often difficult because of the minimum apical bone available. In particular, the interradicular septum, which often represents the ideal fixture position, is rarely adequately represented. Preoperative cone-beam scan and the knowledge of anatomical measurements from the present analysis are fundamental before planning immediate postextractive implants in the upper molar area.


Optically Active Flavaglines-Inspired Molecules by a Palladium-Catalyzed Decarboxylative Dearomative Asymmetric Allylic Alkylation.
With the aid of a class of newly discovered Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the Pd-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved with high efficiency [0.2-1.0 mol% Pd2(dba)3/L], good generality, and high enantioselectivity (>30 examples, 82-99% yield and 90-96% ee). Moreover, a diversity-oriented synthesis (DOS) of previously unreachable flavaglines is disclosed. It features a reliable and scalable sequence of the freshly developed Tsuji-Trost-Stoltz AAA, a Wacker-Grubbs-Stoltz oxidation, an intra-benzoin condensation, and a conjugate addition, which allows the efficient construction of the challenging and compact cyclopenta[b]benzofuran scaffold with contiguous stereocenters. This strategy offers a new avenue for developing flavagline-based drugs.


Effects of Zinc Finger Protein A20 on Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation/Anti-Inflammatory Mediators in an Acute Lung Injury/Acute Respiratory Distress Syndrome Rat Model.
BACKGROUND The aim of this study was to investigate the effects of zinc finger protein A20 on lipopolysaccharide (LPS)-induced pulmonary inflammation/anti-inflammatory mediators in an acute lung injury/acute respiratory distress syndrome (ALI/ARDS) rat model. MATERIAL AND METHODS Forty-eight ALI/ARDS rats were selected and assigned into normal saline (NS) (injected with NS), LPS (injected with LPS), LPS-C1 (injected with pEGFP-C1, NS and LPS), and A20 groups (injected with pEGFP-C1-A20, NS, and LPS). The wet/dry (W/D) ratio of rat lung tissues and total protein concentration and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were detected. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were applied to detect the protein and mRNA expressions of A20, IL-10, and TNF-α, respectively. Western blotting was employed to detect the protein expressions of A20, nuclear factor-kappa B (NF-κB) p65 and NF-κB p-P65 in rat lung tissues. RESULTS Compared with the NS group, the W/D ratio of rat lung tissues and total protein concentration and the number of neutrophils in BALF in the other 3 groups increased significantly. The protein and mRNA expressions of A20, IL-10, and TNF-α were significantly higher in the LPS group than in the NS group. The protein and mRNA expressions of A20 and IL-10 were significantly up-regulated and the expression of TNF-α, NF-κB p65, and NF-κB p-P65 was significantly down-regulated in rats injected with A20 compared to those in the LPS group. CONCLUSIONS The study provided evidence that zinc finger protein A20 can alleviate pulmonary inflammation by inhibiting TNF-α, NF-κB p65, and NF-κB p-P65 expressions and promoting IL-10 expression.


An evaluation of coral lophelia pertusa mucus as an analytical matrix for environmental monitoring: A preliminary proteomic study.
For the environmental monitoring of coral, mucus appears to be an appropriate biological matrix due to its array of functions in coral biology and the non-intrusive manner in which it can be collected. The aim of the present study was to evaluate the feasibility of using mucus of the stony coral Lophelia pertusa (L. pertusa) as an analytical matrix for discovery of biomarkers used for environmental monitoring. More specifically, to assess whether a mass-spectrometry-based proteomic approach can be applied to characterize the protein composition of coral mucus and changes related to petroleum discharges at the seafloor. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) screening analyses of orange and white L. pertusa showed that the mucosal protein composition varies significantly with color phenotype, a pattern not reported prior to this study. Hence, to reduce variability from phenotype difference, L. pertusa white individuals only were selected to characterize in more detail the basal protein composition in mucus using liquid chromatography, mass spectrometry, mass spectrometry (LC-MS/MS). In total, 297 proteins were identified in L. pertusa mucus of unexposed coral individuals. Individuals exposed to drill cuttings in the range 2 to 12 mg/L showed modifications in coral mucus protein composition compared to unexposed corals. Although the results were somewhat inconsistent between individuals and require further validation in both the lab and the field, this study demonstrated preliminary encouraging results for discovery of protein markers in coral mucus that might provide more comprehensive insight into potential consequences attributed to anthropogenic stressors and may be used in future monitoring of coral health.


An Adaptive Particle Weighting Strategy for ECG Denoising Using Marginalized Particle Extended Kalman Filter: An Evaluation in Arrhythmia Contexts.
Model-based Bayesian frameworks have a common problem in processing electrocardiogram (ECG) signals with sudden morphological changes. This situation often happens in the case of arrhythmias where ECGs do not obey the predefined state models. To solve this problem, in this paper, a model-based Bayesian denoising framework is proposed using marginalized particle-extended Kalman filter (MP-EKF), variational mode decomposition, and a novel fuzzy-based adaptive particle weighting strategy. This strategy helps MP-EKF to perform well even when the morphology of signal does not comply with the predefined dynamic model. In addition, this strategy adapts MP-EKF's behavior to the acquired measurements in different input signal to noise ratios (SNRs). At low input SNRs, this strategy decreases the particles' trust level to the measurements while increasing their trust level to a synthetic ECG constructed with the feature parameters of ECG dynamic model. At high input SNRs, the particles' trust level to the measurements is increased and the trust level to synthetic ECG is decreased. The proposed method was evaluated on MIT-BIH normal sinus rhythm database and compared with EKF/EKS frameworks and previously proposed MP-EKF. It was also evaluated on ECG segments extracted from MIT-BIH arrhythmia database, which contained ventricular and atrial arrhythmia. The results showed that the proposed algorithm had a noticeable superiority over benchmark methods from both SNR improvement and multiscale entropy based weighted distortion (MSEWPRD) viewpoints at low input SNRs.


Polarization-basis tracking scheme for quantum key distribution using revealed sifted key bits.
The calibration of the polarization basis between the transmitter and receiver is an important task in quantum key distribution. A continuously working polarization-basis tracking scheme (PBTS) will effectively promote the efficiency of the system and reduce the potential security risk when switching between the transmission and calibration modes. Here, we proposed a single-photon level continuously working PBTS using only sifted key bits revealed during an error correction procedure, without introducing additional reference light or interrupting the transmission of quantum signals. We applied the scheme to a polarization-encoding BB84 QKD system in a 50 km fiber channel, and obtained an average quantum bit error rate (QBER) of 2.32% and a standard derivation of 0.87% during 24 h of continuous operation. The stable and relatively low QBER validates the effectiveness of the scheme.


Assessment of the Knowledge of Blast Injuries Management among Physicians Working in Tripoli Hospitals (Libya).
Introduction No study on hospital staff preparedness for managing blast injuries has been conducted in Libya. The internal conflict in Libya since 2011 and the difficulties faced by the hospitals has highlighted the need for such studies. Hypothesis Physicians working in Tripoli (capital city Libya) hospitals are inadequately prepared for the management of blast injuries. A survey was conducted in all 13 hospitals in Tripoli between June 2014 and May 2015 by using interviews based on a questionnaire consisting of 29 questions covering physicians' education related to blast injury, hospital management of mass casualties, and aspects of hospital preparedness for such incidents. Of 3,799 physicians working in Tripoli hospitals, 607 physicians were interviewed (16.0%). All but one of the physicians reported that there was no disaster response plan, none of them had read such a plan, 496 (81.7%) reported that hospitals were not prepared, and 471 (77.6%) that hospitals were not equipped for blast injuries. Though 414 (68.2%) reported that radiological equipment was available, 597 (98.3%) revealed that hospitals do not adopt training for blast injury. Only 39 (6.4%) had received professional training, though 183 (30.1%) were seeing blast injury patients at least once a week in their daily practice. Nevertheless, 185 (30.5%) had previous knowledge and experience in blast injuries management and 338 (55.70%) were aware of the major physical findings, but only 75 (12.4%) were following specific guidelines. According to approximately one-third of the physicians (192; 31%), staff and patient safety were not priorities for the hospital administration. Almost all (606; 99.9%) revealed that personal protective equipment for chemical and nuclear accidents was not available. Preparedness for blast injuries in Tripoli hospitals is seriously deficient. Planning optimized blast and disaster management in Libya is essential. Oun AM , Hadida EM , Stewart C . Assessment of the knowledge of blast injuries management among physicians working in Tripoli hospitals (Libya). Prehosp Disaster Med. 2017;32(3):311-316.


A Compound Heterozygous Mutation in Calpain 1 Identifies a New Genetic Cause for Spinal Muscular Atrophy Type 4 (SMA4).
Spinal Muscular Atrophy (SMA) is a heterogeneous group of neuromuscular diseases characterized by degeneration of anterior horn cells of the spinal cord, leading to muscular atrophy and weakness. Although the major cause of SMA is autosomal recessive exon deletions or loss-of-function mutations of survival motor neuron 1 (SMN1) gene, next generation sequencing technologies are increasing the genetic heterogeneity of SMA. SMA type 4 (SMA4) is an adult onset, less severe form of SMA for which genetic and pathogenic causes remain elusive.Whole exome sequencing in a 30-year-old brother and sister with SMA4 identified a compound heterozygous mutation (p. G492R/p. F610C) in calpain-1 (CAPN1). Mutations in CAPN1 have been previously associated with cerebellar ataxia and hereditary spastic paraplegia. Using skin fibroblasts from a patient bearing the p. G492R/p. F610C mutation, we demonstrate reduced levels of CAPN1 protein and protease activity. Functional characterization of the SMA4 fibroblasts revealed no changes in SMN protein levels and subcellular distribution. Additional cellular pathways associated with SMA remain unaffected in the patient fibroblasts, highlighting the tissue specificity of CAPN1 dysfunction in SMA4 pathophysiology. This study provides genetic and functional evidence of CAPN1 as a novel gene for the SMA4 phenotype and expands the phenotype of CAPN1 mutation disorders.


Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias.
The 12.6-kDa FK506-binding protein (FKBP12.6) is considered to be a key regulator of the cardiac ryanodine receptor (RyR2), but its precise role in RyR2 function is complex and controversial. In the present study we investigated the impact of FKBP12.6 removal on the properties of the RyR2 channel and the propensity for spontaneous Ca(2+) release and the occurrence of ventricular arrhythmias. Single channel recordings in lipid bilayers showed that FK506 treatment of recombinant RyR2 co-expressed with or without FKBP12.6 or native canine RyR2 did not induce long-lived subconductance states. [(3)H]Ryanodine binding studies revealed that coexpression with or without FKBP12.6 or treatment with or without FK506 did not alter the sensitivity of RyR2 to activation by Ca(2+) or caffeine. Furthermore, single cell Ca(2+) imaging analyses demonstrated that HEK293 cells co-expressing RyR2 and FKBP12.6 or expressing RyR2 alone displayed the same propensity for spontaneous Ca(2+) release or store overload-induced Ca(2+) release (SOICR). FK506 increased the amplitude and decreased the frequency of SOICR in HEK293 cells expressing RyR2 with or without FKBP12.6, indicating that the action of FK506 on SOICR is independent of FKBP12.6. As with recombinant RyR2, the conductance and ligand-gating properties of single RyR2 channels from FKBP12.6-null mice were indistinguishable from those of single wild type channels. Moreover, FKBP12.6-null mice did not exhibit enhanced susceptibility to stress-induced ventricular arrhythmias, in contrast to previous reports. Collectively, our results demonstrate that the loss of FKBP12.6 has no significant effect on the conduction and activation of RyR2 or the propensity for spontaneous Ca(2+) release and stress-induced ventricular arrhythmias.


Linguistic Materials and Metrics for the Creation of Well-Controlled Swedish Speech Perception Tests.
Purpose As factors influencing human word perception are important in the construction of speech perception tests used within the speech and hearing sciences, the purposes of this study were as follows: first, to develop algorithms that can be used to calculate different types of word metrics that influence the speed and accuracy of word perception and, second, to create a database in which those word metrics were calculated for a large set of Swedish words. Method Based on a revision of a large Swedish phonetic dictionary, data and algorithms were developed by which various frequency metrics, word length metrics, semantic metrics, neighborhood metrics, phonotactic metrics, and orthographic transparency metrics were calculated for each word in the dictionary. Of the various word metric algorithms used, some were Swedish language reimplementations of previously published algorithms, and some were developed in this study. Results The results of this study have been gathered in a Swedish word metric database called the AFC-list. The AFC-list consists of 816,404 phonetically transcribed Swedish words, all supplied with the word metric data calculated. The full AFC-list has been made publicly available under the Creative Commons Attribution 4.0 International license. Conclusion The results of this study constitute an extensive linguistic resource for the process of selecting test items in new well-controlled speech perception tests in the Swedish language. Supplemental Material https://doi.org/10.23641/asha.8330009.


Phage Therapy in a 16-Year-Old Boy with Netherton Syndrome.
Netherton syndrome (NS) is a rare autosomal recessive disorder, characterized by a classical triad of clinical features, including congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis coupled with frequent bacterial infections (1). The genetic basis for the disease has been recently identified with mutations in gene SPINK5, which is involved in the regulation of formation of skin barriers. We report on a 16-year-old male with all the typical manifestations of NS, including atopic diathesis and ongoing serious staphylococcal infections and allergy to multiple antibiotics whose family sought help at the Eliava Phage Therapy Center when all other treatment options were failing. Treatment with several antistaphylococcal bacteriophage preparations led to significant improvement within 7 days and very substantial changes in his symptoms and quality of life after treatment for 6 months, including return visits to the Eliava Phage Therapy Center after 3 and 6 months of ongoing use of phage at home.


Inhomogeneous fluid of penetrable-spheres: Application of the random phase approximation.
The focus of the present work is the application of the random phase approximation (RPA), derived for inhomogeneous fluids [Frydel and Ma, Phys. Rev. E 93, 062112 (2016)], to penetrable-spheres. As penetrable-spheres transform into hard-spheres with increasing interactions, they provide an interesting case for exploring the RPA, its shortcomings, and limitations, the weak- versus the strong-coupling limit. Two scenarios taken up by the present study are a one-component and a two-component fluid with symmetric interactions. In the latter case, the mean-field contributions cancel out and any contributions from particle interactions are accounted for by correlations. The accuracy of the RPA for this case is the result of a somewhat lucky cancellation of errors.


Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.
The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc.


Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans.
In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinson's disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.


Viral spillover risk increases with climate change in High Arctic lake sediments.
The host spectrum of viruses is quite diverse, as they can sustainedly infect a few species to several phyla. When confronted with a new host, a virus may even infect it and transmit sustainably in this new host, a process called 'viral spillover'. However, the risk of such events is difficult to quantify. As climate change is rapidly transforming environments, it is becoming critical to quantify the potential for spillovers. To address this issue, we resorted to a metagenomics approach and focused on two environments, soil and lake sediments from Lake Hazen, the largest High Arctic freshwater lake in the world. We used DNA and RNA sequencing to reconstruct the lake's virosphere in both its sediments and soils, as well as its range of eukaryotic hosts. We then estimated the spillover risk by measuring the congruence between the viral and the eukaryotic host phylogenetic trees, and show that spillover risk increases with runoff from glacier melt, a proxy for climate change. Should climate change also shift species range of potential viral vectors and reservoirs northwards, the High Arctic could become fertile ground for emerging pandemics.


Exploring motor cortical plasticity using transcranial magnetic stimulation in humans.
It is generally accepted that functional properties of the motor cortex in adult humans can be altered through behavioral or pharmacological manipulations, as well as in some pathological conditions. The ability and capacity of adult human cortex to undergo any adaptive or reorganizational changes is referred to as plasticity. Much of the evidence concerning motor cortical plasticity have been derived from studies using the non-invasive technique of transcranial magnetic stimulation (TMS). TMS has proven to be a suitable tool to explore representational plasticity and to interact with neuronal activity in settings of induction protocols either alone or coupled with altered sensory inputs. Furthermore, plastic changes induced by motor learning protocols have attracted particular interest because of their relevance in functional recovery. Recent studies support the view that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. Purposeful modulation of motor cortical plastic changes by manipulative TMS protocols may offer useful rehabilitative strategies in patients with chronic motor deficits.


Modulating the Cellular Immune Response of Oligonucleotides by Brush Polymer-Assisted Compaction.
Unwanted stimulation of the innate immune system by foreign nucleic acids has been one of the major barriers preventing bioactive sequences from reaching market. Foreign nucleic acids can be recognized by multiple pattern recognition receptors (PRRs), which trigger a signaling cascade to activate host defense systems, leading to a range of side effects. This study demonstrates that polyethylene glycol (PEG)-modified DNA strands can greatly reduce the activation of the innate immune system, and the extent of reduction is dependent upon polymer architecture. Highly branched brushes with long PEG side chains achieve the best suppression by blocking PRR interactions via a local steric effect. Interestingly, the brush polymer creates little barrier toward DNA-DNA interaction. Quantification of inflammatory cytokines in both mRNA and protein levels as well as the extent of cellular uptake shows a direct correlation between steric congestion and reduction of cellular immune response. These results suggest that the brush architecture offers unique advantages for PEGylating oligonucleotides in the context of minimizing unwanted immune system activation.


Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis.
This databank-based, multicenter study compared all stroke patients with IV tissue plasminogen activator aged > or = 80 years (n = 38) and those < 80 years old (n = 287). Three-month mortality was higher in older patients. Favorable outcome (modified Rankin scale < or = 1) and intracranial hemorrhage (asymptomatic/symptomatic/fatal) were similarly frequent in both groups. Logistic regression showed that stroke severity, time to thrombolysis, glucose level, and history of coronary heart disease independently predicted outcome, whereas age did not.


Progress on diabetic cerebrovascular diseases.
Diabetic cerebrovascular diseases are defined as cerebral vascular diseases induced by diabetes with sugar, fat and a series of nutrient substance metabolic disorders, resulting in intracranial large and small vessel diseases. About 20%-40% patients with type 2 diabetes suffer from cerebral blood vessel diseases. Diabetic cerebrovascular diseases are the main causes of death in patients with diabetes mellitus. The major clinical manifestations are asymptomatic cerebral atherosclerosis, stroke, cerebral small vessel disease and acute cerebral vascular disease. The pathogenesis, clinical characteristics, treatment and prognosis of diabetic cerebrovascular disease are obviously different from non-diabetic cerebral vascular diseases. This paper will focus on the diabetic cerebrovascular disease, including its latest research progress. Diabetic cerebral large vascular disease and diabetic cerebral small vessel disease will be reviewed here.


Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases.
Use of the image-guided stereotactic brain biopsy has facilitated the diagnosis of previously inaccessible lesions with both safety and reliability. However, few studies have assessed the diagnostic yield of frozen section evaluation of the initial stereotactic target (FS-0). We describe our experience with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of FS-0. Retrospective study of 188 stereotactic brain biopsies from 185 patients. Tertiary referral center with a high volume of neurosurgical cases including image-guided stereotactic brain biopsies. One hundred eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a 58-month period. The patients studied included 107 males and 78 females (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0 included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28 (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in diagnosis occurred in three cases (1.7%). We conclude that (1) because 58 (33%) of 177 diagnosed cases in our series would have been potentially misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen section evaluation or cytologic examination of material at the time of surgery should be performed routinely to ensure that adequate tissue has been obtained for purposes of diagnosis; (2) taking up to four biopsies increases the diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are more likely to be definitively diagnosed at FS-0 than non-neoplastic lesions.


Vitamin D status of female UAE college students and associated risk factors.
Vitamin D deficiency is now recognized as a pandemic with implications for bone health and chronic diseases. The study investigated the vitamin D status and risk factors of subnormal serum vitamin D levels in female college students. Cross-sectional study. American University of Sharjah, United Arab Emirate. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured for the participating female undergraduate college students using a radioimmunoassay kit. All participants answered a questionnaire that included 30 questions, which covered among others the demographic information, dietary intake, sun exposure and autoimmune diseases. Undergraduate college female students (n, 480), aged 18-26 years. Overall, 47.92% had suboptimal serum vitamin D levels. Results indicated that vitamin D deficiency and other health problems are prevalent among female university students. Risk factors included: wearing hijab by 37.5% of the students that might have interfered with the penetration of UVB radiation into the skin, short time sun exposure, use of sunscreens and limited intake of foods rich in vitamin D. Vitamin D deficiency is a problem in female college students due to lifestyle, and avoidance of sun exposure. Poor vitamin D status has been associated with increased risk for development of several autoimmune diseases, and other health conditions. This problem needs to be addressed, where prevention of future health consequences in this young group is still possible.


The Impact of Thymidylate Synthase and Methylenetetrahydrofolate Reductase Genotypes on Sensitivity to 5-Fluorouracil Treatment in Colorectal Cancer Cells.
5-fluorouracil (5-FU) is one of the major components of many standard regimens for chemotherapy of colorectal cancer (CRC) and some other malignancies. Given the known relationship between thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) activity and 5-FU metabolism, this study investigated the impact of selected functional polymorphisms of the TS and MTHFR genes on chemotherapy resistance in 5 human CRC cell lines. HCT116, SW1116, HT29/219, LS180, and Caco-2 CRC cells were cultured as monolayer and their chemosensitivity to 5-FU, oxaliplatin, and irinotecan was determined by MTT assay. Genomic DNA was extracted from the cultured cells, and a 6-bp insertion or deletion (6-bp ins/del) polymorphism in 3´-UTR of the TS gene was determined by the PCR-RFLP method. Genotyping of MTHFR 677 C/T and 1298A/C single nucleotide polymorphism (SNP) was also performed by MS-PCR and PCR-RFLP, respectively. Caco-2 with the homozygous TS 6-bp ins/ins and MTHFR 677 T/T and 1298 C/C genotype, was the most 5-FU resistant cell line. HCT116 with the homozygous TS 6-bp del/del and MTHFR 1298 A/A and heterozygous MTHFR 677 C/T genotype was the least 5-FU resistant cell. LS180, the second most 5-FU resistant cell line, was heterozygous for all three polymorphic sits. HT29/219 and SW1116 cells with homozygous TS 6-bp ins/ins and heterozygous MTHFR 677 C/T and 1298 A/C genotypes had intermediate 5-FU sensitivity. The results indicate that TS 3´-UTR 6-bp insertion and MTHFR 677T and 1298C alleles increase 5-FU resistance in CRC cells. No relationship was observed between TS and MTHFR genotypes and oxaliplatin or irinotecan sensitivity in these cells.


NG2 expression in NG2 glia is regulated by binding of SoxE and bHLH transcription factors to a Cspg4 intronic enhancer.
NG2 is a type 1 integral membrane glycoprotein encoded by the Cspg4 gene. It is expressed on glial progenitor cells known as NG2 glial cells or oligodendrocyte precursor cells that exist widely throughout the developing and mature central nervous system and vascular mural cells but not on mature oligodendrocytes, astrocytes, microglia, neurons, or neural stem cells. Hence NG2 is widely used as a marker for NG2 glia in the rodent and human. The regulatory elements of the mouse Cspg4 gene and its flanking sequences have been used successfully to target reporter and Cre recombinase to NG2 glia in transgenic mice when used in a large 200 kb bacterial artificial chromosome cassette containing the 38 kb Cspg4 gene in the center. Despite the tightly regulated cell type- and stage-specific expression of NG2 in the brain and spinal cord, the mechanisms that regulate its transcription have remained unknown. Here, we describe a 1.45 kb intronic enhancer of the mouse Cspg4 gene that directed transcription of EGFP reporter to NG2 glia but not to pericytes in vitro and in transgenic mice. The 1.45 kb enhancer contained binding sites for SoxE and basic helix-loop-helix transcription factors, and its enhancer activity was augmented cooperatively by these factors, whose respective binding elements were found in close proximity to each other. Mutations in these binding elements abrogated the enhancer activity when tested in the postnatal mouse brain.


Effect of Adalimumab on Refractory Arthritis in Juvenile Idiopathic Inflammatory Myopathy with Anti-MDA5 Autoantibody.
A 10-year-old girl manifested persistent fever, skin rash, leg pain, fatigue, and joint pain. Based on muscle weakness, elevated muscle-derived enzymes, magnetic resonance imaging, and skin biopsy results, the diagnosis was juvenile idiopathic inflammatory myopathies (JIIM). Chest CT was normal; the anti-melanoma differentiation-associated protein-5 (anti-MDA5) autoantibody was positive. Initial manifestations subsided after prednisolone (PSL) and methotrexate treatment. After the PSL dosage was decreased, the patient presented with metacarpophalangeal (MCP) joint pain and swelling in both index fingers, synovial fluid, and signals on power Doppler ultrasound. The arthritis was refractory to cyclosporine and tacrolimus. Radiography showed progressive MCP joint space narrowing and joint erosion. Adalimumab was initiated 14 months after disease onset. There was a mildly increased matrix metalloproteinase-3 (MMP3) level, an erythrocyte sedimentation ratio (ESR), and a normal CRP level. Adalimumab resulted in decreased MCP joint pain and swelling. PSL was discontinued 10 months after adalimumab initiation; after 9 more months of adalimumab, there were no significant ultrasonography findings. MMP3 and ESR levels normalized during treatment. Radiography after 2 years of adalimumab showed further progressive MCP joint space narrowing restricting dorsiflexion. This report clarified that anti-MDA5-positive JIIM joint manifestations were due to active synovitis and that adalimumab is required for severe cases. Further experience is needed to determine the pathology, severity, and prognosis of this type of arthritis.


Evaluation of Trigeminocardiac Reflex in Patients Undergoing Elevation of Zygomatic Fractures.
Aim Trigeminocardiac reflex (TCR) manifests as typical hemodynamic perturbations including a sudden lowering of heart rate, mean arterial blood pressure (MABP), cardiac arrhythmias, and asystole. In literature, TCR has been seen during ocular surgeries, Lefort fractures, and craniofacial surgeries. However, the prevalence of the TCR has not been studied in zygomatic complex fractures . The aim of this study was to assess the prevalence of TCR in patients undergoing elevation with/without fixation of zygomatic complex fractures and isolated zygomatic arch fractures under local anesthesia and general anesthesia and to evaluate the prevalence of TCR in different age groups. Materials and methods The study comprised 26 participants diagnosed with zygomatic fractures indicated for surgical intervention. The aim of the study was to find the prevalence of TCR in patients undergoing surgical intervention (elevation of zygomatic complex fractures with/without fixation) under local anesthesia and general anesthesia. The heart rate and blood pressure were measured preoperatively, intraoperatively and postoperatively. Results Variation in heart rate was seen in patients undergoing surgery under local anesthesia and general anesthesia. However, a decrease in the heart rate i.e., bradycardia was noted intra-operatively in 75% of the patients operated under local anesthesia. The prevalence of TCR was noted intra-operatively in 23% of cases operated under general anesthesia. No significant changes were seen in the blood pressure of the patients. Conclusion In our study, we found out that the prevalence of TCR was more in the patients operated under local anesthesia i.e., 75% of patients. Out of the patients operated under general anesthesia i.e., 23% of patients showed TCR. No significant variations in blood pressure were observed in patients operated under local anesthesia or general anesthesia. The prevalence of TCR was found more often in the age group of 31-45 years in our study.


A reexamination of the role of the RAD52 gene in spontaneous mitotic recombination.
The RAD52 gene is required for much of the recombination that occurs in Saccharomyces cerevisiae. One of the two commonly utilized mutant alleles, rad52-2, increases rather than reduces mitotic recombination, yet in other respects appears to be a typical rad52 mutant allele. This raises the question as to whether RAD52 is really necessary for mitotic recombination. Analysis of a deletion/insertion allele created in vitro indicates that the null mutant phenotype is indeed a deficiency in mitotic recombination, especially in gene conversion. The data also indicate that RAD52 is required for crossing-over between at least some chromosomes. Finally, examination of the behavior of a replicating plasmid in rad52-1 strains indicates that the frequency of plasmid integration is substantially reduced from that in wild type, a conclusion consistent with a role for RAD52 in reciprocal crossing-over. Analysis of recombinants arising in rad52-2 strains suggests that this allele may result in the increased activity of a RAD52-independent recombinational pathway.


Heterotic groups of tropical indica rice germplasm.
Four heterotic groups were identified for tropical indica rice germplasm to develop hybrid rice in the tropics based on two studies. Heterotic groups are of fundamental importance in hybrid crop breeding. This study investigated hybrid yield, yield heterosis and combining ability within and among groups based on genetic distance derived from single-nucleotide polymorphism markers. The main objectives of the study were to (1) evaluate the magnitude of yield heterosis among marker-based groups, (2) identify possible heterotic groups for tropical indica hybrid rice, and (3) validate heterotic patterns concluded from a previous study. Seventeen rice parents selected from improved indica germplasm from the tropics with high genetic divergence and 136 derived hybrids were evaluated in five environments. The hybrids had more yield than their parents with an average of 24.1 % mid-parent heterosis. Genotype × environment interaction was the major factor affecting variations in yield and yield heterosis, which raised a necessity and a challenge to develop heterotic rice hybrid adapted to different regions and seasons in the tropics. Yield, yield heterosis and combining ability were significantly increased in inter-group than in intra-group hybrids. Four heterotic groups and three promising hybridization patterns, which could be used in tropical hybrid rice breeding, were identified based on marker-based grouping, yield and yield heterosis analyses in the two studies. The study reveals that molecular markers analysis can serve as a basis for assigning germplasm into heterotic groups and to provide guidelines for parental selection in hybrid rice breeding.


Pain and learning in primary school: a population-based study.
Despite the frequency of pain among children, little is known about its effects on learning and school outcomes. The objective of this study was to quantify the association of pain and academic achievement while taking into account the presence of co-occurring emotional symptoms. A population-based stratified random sample of 1239 students aged 8 to 9 years from primary schools in Melbourne, Australia, was recruited for the Childhood to Adolescence Transition Study. Children indicated sites of pain that had lasted for a day or longer in the past month using a pain manikin. Depressive- and anxiety-related symptoms were assessed using child-reported items. National assessment results for reading and numeracy were used to measure academic achievement. Sixty-five percent of children reported pain in at least 1 body site and 16% reported chronic pain. Increasing number of pain sites was associated with poorer reading scores in a dose-response fashion (β = -3.1; 95% confidence interval -4.9 to -1.3; P < 0.001). The association was only partly attenuated when adjusting for emotional symptoms (β = -2.6; 95% confidence interval -4.5 to -0.8; P < 0.001) and was not moderated by emotional symptoms. Children with chronic pain were a year behind their peers in both reading and numeracy. Among primary school students, pain was associated with lower reading scores even after adjusting for the presence of emotional symptoms. Although population-based longitudinal studies will be required to ascertain consistency and possible causality, grounds exist for considering pain and emotional symptoms in the assessment of children with reading difficulties.


Impact of Low-Dose Hydrocortisone on the Incidence of Atrial Fibrillation in Patients With Septic Shock: A Propensity Score-Inverse Probability of Treatment Weighting Cohort Study.
Atrial fibrillation (AF) is common in the intensive care unit (ICU), notably in patients with septic shock for whom inflammation is an already identified risk factor. The aim of this study was to evaluate the effect of low-dose hydrocortisone on AF occurrence in patients with septic shock. We performed a prospective nonrandomized observational study in 5 academic ICUs in France. From November 2012 to June 2014, all patients ≥16 years having septic shock were included, except those who had a history of AF, had a pacemaker, and/or experienced AF during hospitalization before the onset of shock or in whom the onset of shock occurred prior to admission to the ICU. Hydrocortisone was administered at the discretion of the attending physician. The incidence of AF was compared among patients who received hydrocortisone, and the effect of low-dose hydrocortisone on AF was estimated using the inverse probability treatment weighting method based on propensity scores. A total of 261 patients were included (no-hydrocortisone group, n = 138; hydrocortisone group, n = 123). Atrial fibrillation occurred in 57 (22%) patients. Atrial fibrillation rates were 33 (24%) and 24 (19%) in no-hydrocortisone patients and hydrocortisone patients, respectively. In the weighted sample, the proportion of patients who developed AF was 28.8% in the no-hydrocortisone group and 16.8% in the hydrocortisone group (difference: -11.9%; 95% confidence interval: -23.4% to -0.5%; P = .040). In patients with septic shock, low-dose hydrocortisone was associated with a lower risk of developing AF during the acute phase.


Pathogenesis of abdominal aortic aneurysm.
The pathogenesis of abdominal aortic aneurysm involves many factors acting over time. However, destruction of elastin in the aortic wall is a key event that shifts the load produced by blood pressure on to collagen. This is exacerbated in the presence of hypertension. Smoking and age are further important factors, as is the site; elastic lamellae are relatively less common in the abdominal aorta. Once the shielding effect of elastin is lost, further dilatation and rupture of the aorta depend on the physical properties of the collagen present.


New ternary ligands consisting of an N4 bridging ligand and two terpyridines, and their Co(II) and Ni(II) dinuclear complexes. Structure, redox properties, and reaction with acid.
Two ternary ligands consisting of two 2,2′:6′,2′′-terpyridines and one N4-quadridentate μ2,η(2)-bridging ligand were synthesized. The N4 bridge is 1,4-bis(2-pyridyl)phthalazine in ligand 1, and 3,6-bis(2-pyridyl)pyridazine in ligand 2. Two Co(II) dinuclear complexes [(1)Co2(μ-OH)]3+ and [(2)Co2(μ-OH)]3+, and one Ni(II) dinuclear complex [(1)Ni2(μ-Cl)]3+ were obtained. In the crystal structures of [(1)Co2(μ-OH)]3+ and [(1)Ni2(μ-Cl)]3+, two pyridine rings are twisted around the pyridine-phthalazine bonds to avoid steric repulsion between the hydrogen atoms. The pyridine rings also showed a significant tilt from the octahedral coordination plane, which causes the large positive shift of the first reduction potentials. Upon the addition of a proton, the cobalt dinuclear complexes can release one cobalt ion selectively, and the dinuclear complexes can be easily restored by the addition of a tertiary amine.


In Vitro Effects of Combining Genistein with Aromatase Inhibitors: Concerns Regarding Its Consumption during Breast Cancer Treatment.
The third-generation of aromatase inhibitors (AIs)-Exemestane (Exe), Letrozole (Let), and Anastrozole (Ana)-is the main therapeutic approach applied for estrogen receptor-positive (ER+) breast cancer (BC), the most common neoplasm in women worldwide. Despite their success, the development of resistance limits their efficacy. Genistein (G), a phytoestrogen present in soybean, has promising anticancer properties in ER+ BC cells, even when combined with anticancer drugs. Thus, the potential beneficial effects of combining G with AIs were investigated in sensitive (MCF7-aro) and resistant (LTEDaro) BC cells. The effects on cell proliferation and expression of aromatase, ERα/ERβ, and AR receptors were evaluated. Unlike the combination of G with Ana or Let, which negatively affects the Ais' therapeutic efficacy, G enhanced the anticancer properties of the steroidal AI Exe, increasing the antiproliferative effect and apoptosis relative to Exe. The hormone targets studied were not affected by this combination when compared with Exe. This is the first in vitro study that highlights the potential benefit of G as an adjuvant therapy with Exe, emphasizing, however, that soy derivatives widely used in the diet or applied as auxiliary medicines may increase the risk of adverse interactions with nonsteroidal AIs used in therapy.


Structural elucidation of the protein- and membrane-binding properties of the N-terminal tail domain of human annexin II.
The conformational preferences and the solution structure of AnxII(N31), a peptide corresponding to the full-length sequence (residues 1-31) of the human annexin II N-terminal tail domain, were investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AnxII(N31) adopts a mainly alpha-helical conformation in hydrophobic or membrane-mimetic environments, while a predominantly random structure is adopted in aqueous buffer. In contrast to previous results of the annexin I N-terminal domain peptide [Yoon et al. (2000) FEBS Lett. 484, 241-245], calcium ions showed no effect on the structure of AnxII(N31). The NMR-derived structure of AnxII(N31) in 50% TFE/water mixture showed a horseshoe-like fold comprising the N-terminal amphipathic alpha-helix, the following loop, and the C-terminal helical region. Together, the results establish the first detailed structural data on the N-terminal tail domain of annexin II, and suggest the possibility of the domain to undergo Ca(2+)-independent membrane-binding.


Shared antigenic determinants between two distinct classes of proteins in cells infected with herpes simplex virus.
Guinea pig antisera and mouse monoclonal antibodies against a 40,000-molecular-weight nucleocapsid protein (p40) of herpes simplex virus types 1 and 2 immunoprecipitated 40,000- and 80,000-molecular-weight classes of soluble proteins from infected cell extracts. The soluble 40,000-molecular-weight protein class (intracellular p40) appeared as a cluster of three to four closely spaced bands of proteins having molecular weights ranging between 39,000 and 45,000, whereas the soluble 80,000-molecular-weight protein class (intracellular p80) appeared as a doublet of bands. The peptide map of intracellular p40 closely resembled the maps of the p40 and p45 proteins of nucleocapsids, but it showed both differences and similarities when compared with the peptide map of intracellular p80. Pulse-chase experiments suggested that intracellular p80 was not a precursor of intracellular p40. We conclude that the intracellular p40 and p80 protein classes share common antigenic determinants, presumably reflecting similar amino acid sequences, although they have distinct differences in protein structure.


Specific detection of pathogenic Yersinia enterocolitica by two-step PCR using hot-start and DMSO.
A pair of polymerase chain reaction (PCR) primers, YC1 and YC2, selected from the sequence of the invasin locus (inv) of Y. enterocolitica, has been evaluated for specific detection of pathogenic Y. enterocolitica by PCR. The primers were hybridized at high stringency conditions to DNA from 65 pathogenic Y. enterocolitica, 16 non-pathogenic Y. enterocolitica, 18 other Yersinia and 124 non-Yersinia strains. YC2 hybridized to the pathogenic Y. enterocolitica only, while YC1 hybridized weakly to nine non-Yersinia as well. In a PCR with annealing at 64 degrees C all Y. enterocolitica, pathogenic and non-pathogenic, were positive. However, DNA from 60 non-Y. enterocolitica was amplified. With annealing at 72 degrees C, 10 non-pathogenic Y. enterocolitica and 41 non-Y. enterocolitica were positive. When a two-step PCR assay with annealing at 72 degrees C, hot-start and 1% dimethylsulphoxide (DMSO) were used, only DNA from the pathogenic Y. enterocolitica were amplified. The limit of detection was shown for four different strains to be less than 10 cells per PCR tube.


Are pharmacists ready for a greater role in travel health? An evaluation of the knowledge and confidence in providing travel health advice of pharmacists practicing in a community pharmacy chain in Alberta, Canada.
Patients often consult community pharmacists for medication needs related to travel, but little is known of pharmacists' knowledge and readiness to provide this care. The aim of this study was to evaluate pharmacists' knowledge in travel health, and to assess their confidence in providing travel-related advice to patients. A web-based survey was developed and distributed to 84 pharmacists practicing in a mid-size pharmacy chain in Alberta, Canada. The survey included knowledge and confidence assessment components. To assess knowledge, pharmacists were provided two cases, along with multiple-choice questions examining pre-travel risk assessment, and advice on travel at altitude, vaccines, malaria, travelers' diarrhea, and other potential travel health risks. Confidence was assessed by asking respondents to report their level of confidence in answering each knowledge assessment question and providing travel advice overall, using a 5-point Likert scale. Respondents were also asked to indicate preferred means for receiving additional training in travel health. A total of 53 pharmacists responded to the survey, with a response rate of 63%. Most (61%) indicated that they had some level of training in travel health and 69% counseled on travel health more than once a month. Only one respondent correctly answered all six questions in the knowledge assessment section. The mean knowledge score (proportion of correct answers, unaided) for the group was 27%. However, the majority (66%) felt confident that they would know where to seek the information required to answer the questions. Overall confidence in this group of pharmacists was determined to be low, with only 21% of respondents reporting that they felt highly confident in providing travel health advice. Travel health is becoming an increasingly common topic of discussion between patients and pharmacists. This study suggests that pharmacists' baseline knowledge of travel health may be incomplete, affecting their confidence in providing this advice. Undergraduate and continuing education training programs must expand travel health curricula to meet this growing need.


An ontology for carcinoma classification for clinical bioinformatics.
There are a plenty of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications involve entities which exist at various anatomical levels of granularity and in order to apply such classifications to the Electronic Health Care Records, one needs to build ontologies which are not only based on the formal principles but also take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues in a way that inferences drawn upon the ontologies would be helpful in interpreting and inferring on the entities which exist at different anatomical levels of granularity. Our case study is on the colon carcinoma, one of the commonest carcinomas prevalent within the European population.


Evidence for a complex life cycle and endospore formation in the attached, filamentous, segmented bacterium from murine ileum.
Light and electron microscope observations showed that the filamentous, segmented bacterium commonly found attached to the ileal epithelium of rats and mice undergoes a complex life cycle. Filaments comprising up to 90 segments were attached to the microvillous border of absorptive epithelial cells by a specialized terminal holdfast segment. Starting at the free end of the filament and progressing toward the attached end, undifferentiated segments were converted into reproductive or mother segments. Within each mother cell two new holdfast segments developed. As the holdfasts matured, their mother cells degenerated and released them into the intervillar space where they attached, grew, and divided to produce new segmented filaments. Alternately, in some filaments, newly formed but not yet released holdfasts were converted into endospores, which were released in the same manner as holdfasts, presumably to spread the bacterial colony to other members of the rodent population.


Cytoprotective effect of neuropeptides on cancer stem cells: vasoactive intestinal peptide-induced antiapoptotic signaling.
Cancer stem cells (CSCs) are increasingly considered to be responsible for tumor initiation, metastasis and drug resistance. The drug resistance mechanisms activated in CSCs have not been thoroughly investigated. Although neuropeptides such as vasoactive intestinal peptide (VIP) can promote tumor growth and activate antiapoptotic signaling in differentiated cancer cells, it is not known whether they can activate antiapoptotic mechanisms in CSCs. The objectives of this study are to unravel the cytoprotective effects of neuropeptides and identify antiapoptotic mechanisms activated by neuropeptides in response to anticancer drug treatment in CSCs. We enriched and purified CSCs (CD44+/high/CD24-/low or CD133+ population) from breast and prostate cancer cell lines, and demonstrated their stemness phenotype. Of the several neuropeptides tested, only VIP could protect CSCs from drug-induced apoptosis. A functional correlation was found between drug-induced apoptosis and dephosphorylation of proapoptotic Bcl2 family protein BAD. Similarly, VIP-induced cytoprotection correlated with BAD phosphorylation at Ser112 in CSCs. Using pharmacological inhibitors and dominant-negative proteins, we showed that VIP-induced cytoprotection and BAD phosphorylation are mediated via both Ras/MAPK and PKA pathways in CSCs of prostate cancer LNCaP and C4-2 cells, but only PKA signaling was involved in CSCs of DUVIPR (DU145 prostate cancer cells ectopically expressing VIP receptor) and breast cancer MCF7 cells. As each of these pathways partially control BAD phosphorylation at Ser112, both have to be inhibited to block the cytoprotective effects of VIP. Furthermore, VIP is unable to protect CSCs that express phosphorylation-deficient mutant-BAD, suggesting that BAD phosphorylation is essential. Thus, antiapoptotic signaling by VIP could be one of the drug resistance mechanisms by which CSCs escape from anticancer therapies. Our findings suggest the potential usefulness of VIP receptor inhibition to eliminate CSCs, and that targeting BAD might be an attractive strategy for development of novel therapeutics.


The active participation of elderly patients in traditional Chinese medicine consultations as means to creating a community of practice: A case study in Hong Kong.
Despite its historic role in Chinese society and its popularity with an elderly Chinese population, limited research has explored the discursive practices of Traditional Chinese Medicine (TCM). Our analysis of practitioner-patient interactions illustrated the reasons why TCM is widely welcomed by a specific patient group. This paper adopted the concept of Community of Practice (CoP) as a theoretical framework to document how patients interact with TCM practitioners to construct meaning through a process of participation and reification. This study aimed to explore how patients in a medical consultation context developed an understanding of their conditions and how they strategically used medical terminology to enact meaningful exchanges to realise their CoP. An inductive qualitative discourse analysis was conducted to for nine elderly patients (i.e., age > 65) in Hong Kong to demonstrate the role that a CoP played in a joint process of knowledge construction to promote a patient-centred practice and foster the active participation of the patients. TCM practitioners can develop specific communication skills to promote their patients' CoP, which will improve patient-centred care, empower patients to actively engage in their treatments and result in higher levels of patient satisfaction.


Cellulomonas dongxiuzhuiae sp. nov., Cellulomonas wangleii sp. nov. and Cellulomonas fengjieae sp. nov., isolated from the intestinal contents of Marmota himalayana.
Six Gram-stain-positive, aerobic or facultative anaerobic, catalase-positive, urease- and oxidase-negative, rod-shaped bacteria (zg-ZUI157T/zg-ZUI40, zg-ZUI222T/zg-ZUI199 and zg-ZUI188T/ zg-ZUI168) were characterized by a polyphasic approach. Optimal growth of the six strains was observed at pH 7.0 and 28 °C. Phylogenetic analyses based on the 16S rRNA gene and 247 core genes revealed that they belong to genus Cellulomonas. The three type strains have low digital DNA-DNA hybridization (19.3-30.1%) and average nucleotide identity values (78.0-85.5%) with all available genomes in the genus Cellulomonas, and a DNA G+C content range of 73.0-74.6 mol%. The major fatty acids detected in strain pairs zg-ZUI157T/zg-ZUI40 and zg-ZUI 222T/zg-ZUI199 were C16:0, anteiso-C15:0 and anteiso A-C15:1, and C16:0, anteiso-C15:0, anteiso A-C15:1 and anteiso-C17:0 in strain pair zg-ZUI188T/zg-ZUI168. Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol mannosides were the major polar lipids detected in the three novel species. MK-9(H4) was the predominant quinone detected in strains zg-ZUI222T (87.4 %) and zg-ZUI188T (91.4 %), and MK-9(H4) (49.1 %) and MK-8 (43.4 %) in strain zg-ZUI157T. The cell-wall sugars detected in the three novel species mainly contained rhamnose. The cell-wall peptidoglycan type of the three novel species was A4β, with an inferred l-Orn-d-Asp interpeptide bridge for strains zg-ZUI157T and zg-ZUI222T, and l-Orn-d-Glu for strain zg-ZUI188T. Based on the results of the phenotypic, phylogenetic, genomic hybridization, average nucleotide identity and chemotaxonomic analyses, the six strains should be classified as belonging to three novel Cellulomonas species, for which the names Cellulomonas dongxiuzhuiae sp. nov. (zg-ZUI157T=GDMCC 1.2559T=KCTC 49678T), Cellulomonas wangleii sp. nov. (zg-ZUI222T=GDMCC 1.2501T=KCTC 49675T) and Cellulomonas fengjieae sp. nov. (zg-ZUI188T=GDMCC 1.2563T=KCTC 49674T) are proposed.


Mulch preferences of the Asian cockroach (Dictyoptera: Blattellidae).
Mulch preferences of the Asian cockroach, Blattella asahinai Mizukubo, were determined in a series of laboratory experiments. Because this species is a peridomestic pest, mulch preferences may be a key part of an integrated pest management program for homeowners. Five mulches were used: cypress, oak leaf litter, pine straw, rubber, and topsoil. Large arena experiments showed that adult male Asian cockroaches preferred oak leaf litter and pine straw, while adult females preferred oak leaf litter and rubber mulches. Nymphal stages preferred rubber (48.3-62.5% for small and medium instars, respectively) to all other mulches. All stages of the Asian cockroach showed very little preference to topsoil (0%) and cypress mulch (6.3%). Ebeling choice box tests confirmed lack of preference or repellency of adult males to topsoil (17.8 +/- 3.6%) and rubber mulch (15.7 +/- 3.6%). Continuous exposure experiments indicated that pine straw was significantly more toxic to adult males than other mulches (66.7 +/- 18.4% mortality at 7 d). Mulch preferences of the Asian cockroach may be mediated by characteristics of the interstitial spaces in the different mulches. Rubber mulch afforded smaller, more humid spaces that were inaccessible to adults. Because cypress mulch was least preferred by nymphs and adults, use of cypress mulch in an integrated pest management program around homes may help to reduce Asian cockroach populations and limit insecticide exposure to humans, animals, and the environment.