Clinical outcomes of minimally invasive transforaminal lumbar interbody fusion via a novel tubular retractor.
To assess the feasibility and clinical results of microscopic minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using a novel tapered tubular retractor that preserves the multifidus. A total of 122 patients underwent MIS-TLIF using a tapered tubular retractor system from March 2016 to August 2017. Perioperative parameters and follow-up outcomes were reviewed. The follow-up period was 23.95 ± 1.43 months. The operative time averaged 130.48 ± 34.44 minutes. The estimated blood loss was 114.10 ± 96.70 mL. The mean time until ambulation was 16.33 ± 6.29 hours. The average visual analogue scale (leg/waist) and Oswestry Disability Index scores (preoperative to last follow-up) improved from 4.93 ± 2.68/3.74 ± 2.28 to 0.34 ± 0.77/0.64 ± 0.74 and from 59.09% ± 22.34 to 17.04% ± 8.49, respectively. At the last follow-up, 98.36% of the patients achieved solid fusion. Cerebrospinal fluid leakage occurred in two cases. The asymptote of the surgeon's learning curve occurred at the 25th case. There were no significant differences between the preoperative qualitative and quantitative analyses of multifidus muscle fatty infiltration and those at the final follow-up. MIS-TLIF can be performed safely and effectively using this tapered tubular retractor system, which helps preserve the multifidus.


Temperature dependence of NMR order parameters and protein dynamics.
The helical subdomain, HP36, of the F-actin-binding headpiece domain of chicken villin, is the smallest naturally occurring polypeptide that folds to a thermostable compact structure. Unconstrained molecular dynamics simulations and constrained molecular dynamics simulations using umbrella sampling are used to study the temperature dependence of internal motions of the backbone amide moieties of HP36. The potential of mean force (PMF) for the N-H bond vector, determined from the constrained simulations, is found to be temperature dependent. A simple analytical expression is derived that describes the temperature dependence of the PMF. The parameters of this model are obtained from the PMF, from the unconstrained molecular dynamics simulations, or from experimental values of the generalized order parameter. The results provide a linkage between experimental and theoretical measures of the temperature dependence of protein motions.


Development and Validation of a High-Fidelity Finite-Element Model of Monopolar Stimulation in the Implanted Guinea Pig Cochlea.
To validate a new electroanatomical model of the implanted guinea pig cochlea against independently obtained in vivo voltage tomography data, and evaluate the validity of exist-ing modeling assumptions on current paths and neural excitation. An in silico model was generated from sTSLIM images and analyzed in COMSOL Multiphysics. Tissue resistivities and boundary conditions were varied to test model sensitivity. The simulation was most sensitive to the resistivities of bone, perilymph, and nerve. Bone tissue in particular should be separated by morphology because different types of bone have different electrical properties. Despite having a strong impact on intrascalar voltages and exit pathways, most boundary conditions, including a new alternative proposed to account for the unmodeled return path, only had a weak effect on neural excitation. The new model demonstrated a strong correlation with the in vivo voltage data. These findings address a long-standing knowledge gap about appropriate boundary conditions, and will help to promote wider acceptance of insights from computational models of the cochlea.


Prognostic Factors and Staging Systems in Hepatocellular Carcinoma.
There are a number of factors that should be taken into consideration when predicting the outcomes and prognosis of hepatocellular carcinoma. Four of the most important factors in determining survival are the severity of the accompanying liver disease, tumor size and number, extension of the tumor into other structures, and presence of metastases. The most common and widely accepted tumor staging systems include these 4 prognostic factors. The staging systems are (1) the tumor-node-metastasis system of the American Joint Committee on cancer, (2) the Okuda system, (3) the Barcelona Clinic Liver Cancer system, (4) the Cancer of the Liver Italian Program score; (5) the recent albumin-bilirubin grading system, and finally (6) the Hong Kong Liver Cancer staging system. The successful staging of patients with hepatocellular carcinoma is difficult because of the many contributing factors to disease. Therefore, in clinical practice, there is no ideal system that can be applicable to every patient in predicting survival. As a general rule, patient and treatment modality selection criteria should be individualized for every patient and should not use an algorithmic approach because aggressive treatments in properly selected patients with hepatocellular carcinoma offer good results. A better approach for increased treatment success is one that is multidisciplinary, that is, one that considers the different variables.


Perspectives on the use of data mining in pharmaco-vigilance.
In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmaco-vigilance methods. Perspectives from both the FDA and the industry are provided. Data mining is a potentially useful adjunct to traditional pharmaco-vigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues.


Affective and behavioral reactions to the violation of limits on alcohol consumption.
The limit violation effect (LVE) was studied by inducing male social drinkers to consume either more or less beer than their prestated limit on alcohol intake. Affective and behavioral reactions to the violation of drinking limits were mediated by attributional style and aspects of drinking restraint. Subjects who reported greater than average levels of self-blaming attributions, restrictions on alcohol intake and cognitive preoccupation with alcohol became depressed and angry after the violation of drinking limits. In contrast to the hypothesized excessive-drinking component of the LVE, subjects who experienced negative affective reactions to the violation ordered fewer shots in a subsequent whiskey-tasting task. Possible conceptual and methodological reasons for observing only the affective component of the LVE are discussed.


Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.
Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.


An Ultrasensitive Fluorescence Assay for the Detection of Halides and Enzymatic Dehalogenation.
Halide assays are important for the study of enzymatic dehalogenation, a topic of great industrial and scientific importance. Here we describe the development of a very sensitive halide assay that can detect less than a picomole of bromide ions, making it very useful for quantifying enzymatic dehalogenation products. Halides are oxidised under mild conditions using the vanadium-dependent chloroperoxidase from Curvularia inaequalis, forming hypohalous acids that are detected using aminophenyl fluorescein. The assay is up to three orders of magnitude more sensitive than currently available alternatives, with detection limits of 20 nM for bromide and 1 μM for chloride and iodide. We demonstrate that the assay can be used to determine specific activities of dehalogenases and validate this by comparison to a well-established GC-MS method. This new assay will facilitate the identification and characterisation of novel dehalogenases and may also be of interest to those studying other halide-producing enzymes.


Factors affecting survival in kidney recipients at kermanshah.
Our aim was to evaluate patient and graft survivals in kidney recipients and factors impacting on survival rates at Kermanshah. This study was done on 712 kidney transplants from 1989 through 2001 in Kermanshah. One of the most important applications of survival analysis is assessing the role of explanatory factors in the studied event. In this study Kaplan-Meier method was used to calculate patient and graft survivals and in order to determine the factors affecting survival, Cox proportional hazard model was used. The iterations in Cox model was four times and the inclusion and exclusion criteria, calculated by forward conditional method were less than 5% and 10%, respectively. Of the recipients, 47.6% were female and most of them (94.4%) had received kidneys from living unrelated donors. One-year patient survivals in recipients from living unrelated donors (LURD) and living related donors (LRD) were 89.4% and 100%, 3-year survivals were 82% and 97.4%, and 10-year survivals were 61.4% and 72%, respectively. In addition, graft survival rates in one year were 85.6% and 97.4%, in three years were 77.2% and 92.3%, and in 10 years were 33.3% and 60.6% in LURD and LRD, respectively. In Cox model, four factors, including the presence of surgical or other complications, known primary disease, and donor-recipient relationship had significant association with patient survival and seven factors, including the presence of surgical complications, known primary disease, donor-recipient relationship, gender, weight, same side transplanted kidney, and donor's age had significant relationship with graft survival. In summary, it can be concluded that patient and donor demographic characteristics and transplantation conditions may affect patient and graft survival. With the use of multivariate regression analysis methods, the characteristics that have high probability for survival can be determined. Controlling these situations, where they have high survival probability, effectively help better treatment and high survival rate.


[Effect of fluid viscosity on the biomechanical sequence of oropharyngeal swallowing in healthy males].
Objective: To confirm the effect of fluid with different viscosity on the normal biomechanical sequence of oropharyngeal swallowing in healthy males. Methods: Fifteen healthy male subjects [(27.7±1.8) years old] were recruited from November 2011 to February 2012 and instructed to swallow 15 ml of water (W), nectar-like fluid (N), and honey-like fluid (H) in an upright sitting position. The sensing system was consisted of tongue pressure sensor sheet, bend sensor, surface electrodes and microphone. They were used to monitor tongue pressure, hyoid activity, surface electromyography (EMG) of swallowing-related muscles and swallowing sound, respectively. The swallowing sound was chosen as the reference time. The significance of biomechanical sequence of structural events was determined by repeated-measures analysis of variance (ANOVA). Results: When swallowing liquid of any consistency, hyoid premotor and suprahyoid muscle electromyography (EMG) appeared synchronously (P>0.05), followed by the simultaneous appearances of hyoid rapid movement, peak time of suprahyoid muscle EMG, onset of infrahyoid muscle EMG, and anterior tongue pressure production (P>0.05). The peak time of infrahyoid muscle EMG was very close to the peak time of anterior tongue pressure (P>0.05), and both of them were earlier than the time that the hyoid reaching the highest position (P<0.05). At last, the time that the hyoid departing the highest position was synchronized with the disappearances of suprahyoid muscle EMG, infrahyoid muscle EMG, and tongue pressure (P>0.05). The tongue pressure production and peak time of tongue pressure arose from anterior to posterior along the midline of hard palate during normal swallowing, with the significances for tongue pressure production between the anterior site and the middle site (W: P=0.035, N: P=0.027, H: P=0.013) as well as the anterior site and the posterior site (W: P<0.001, N: P<0.001, H: P<0.001), while the appearance and peak time of the circumferential tongue pressure were very close (P>0.05). The increase of fluid viscosity did not affect the biomechanical sequence of the above structural physiological movements during normal swallowing. There were statistically significant differences between the hyoid premotor and the onset of suprahyoid muscle EMG when swallowing the honey-like liquid [(-1.03±0.47) and (-0.90±0.50) s] and water[(-0.87±0.32) and (-0.74±0.31) s] (P<0.001). Among the delayed structural events, except for the onset of infrahyoid muscle EMG and the tongue pressure production on the anterior site (P>0.05), the occurrences of all the parameters in swallowing honey-like fluid were significantly later than those in swallowing water (onset of hyoid rapid movement, P=0.007; time of hyoid reaching the highest position, P=0.034; time of hyoid departing the highest position, P=0.041; offset of hyoid movement, P=0.035; peak time of suprahyoid muscle EMG: P=0.040; offset of suprahyoid muscle EMG, P=0.014; peak time of infrahyoid muscle EMG: P=0.042; offset of infrahyoid muscle EMG, P=0.028; peak time of Ch.1: P=0.045; offset of Ch.1: P=0.012; onset of Ch.2: P=0.038; peak time of Ch.2: P=0.009; offset of Ch.2: P=0.034; onset of Ch.3: P=0.043; peak time of Ch.3: P=0.011; offset of Ch.3: P=0.026;onset of Ch.4: P=0.040; peak time of Ch.4: P=0.038; offset of Ch.4: P=0.033; onset of Ch.5: P=0.046; peak time of Ch.5:P=0.028; offset of Ch.5: P<0.001), but not for those between nectar-like fluid and honey-like fluid (P>0.05). Conclusions: The alteration of fluid viscosity did not affect healthy male biomechanical sequence of tongue, hyoid and swallowing-related muscles during normal swallowing. The biomechanics of the oropharyngeal structures is physiologically regulated with the alteration of fluid viscosity to ensure swallowing safely and smoothly.


[Comparison of methods of detection of bovine adenovirus serotype 3 in infected culture of calf kidney cells (MDBK)].
The comparative study of the dynamics of the main antigen (hexon) and viral DNA of the bovine adenovirus type 3 accumulation in the established cell line MDBK under the conditions of single- or multistep cycle of infection has been undertaken. The quantitative immunoelectrophoresis and immunoenzyme assay detected the viral antigens on the late stages of infection in the period of cellular monolayer degradation. The immunofluorescence reaction and histochemical immunoenzyme method detected the antigen in the infected cells concurrently with the primary expression of the viral cytopathic effect. The reaction of the spot molecular hybridization with the [32P]-DNA probes detected the viral DNA considerably earlier than the antigen was detected by the immunological methods, before the appearance of degenerative changes in the infected cells. Preference of the immunoenzyme assay and DNA-probes in diagnosis of the virus are discussed.


Spatiotemporal nonhomogeneous poisson model with a seasonal component applied to the analysis of extreme rainfall.
This paper develops an extension of spatiotemporal models that handle count data using nonhomogeneous Poisson processes. In this new proposal, we incorporate a seasonal cycle component in the definition of the intensity function to control possible effects produced by the occurrence of the event of interest in regular periods. The seasonal cycle can cause problems in estimating the shape parameter of the Weibull and generalized Goel intensity functions. This shape parameter serves to confront the research hypothesis that seeks to identify a trend in the occurrence rate of an event of interest. In the case of the Weibull intensity function, a value significantly equal to one of the shape parameters indicates a constant rate of occurrence, less than one indicates a decreasing rate, and greater than one indicates an increasing rate. In the case of the Goel intensity function, parameter values less than or equal to one indicate a decreasing occurrence rate, and values greater than one indicate the presence of a change point. We also built a spatial model using the Musa-Okumoto intensity function as an alternative to approximate counting processes for which there is a decreasing trend in the occurrence rate of the event of interest. We estimated the parameters of the proposed method from a Bayesian perspective. Finally, we fitted the proposed model and compared it with other approximations to analyze the frequency of extreme rainfall in the northern region of the states of Maranhão and Piauí in northeastern Brazil over ten years. Among the main results, we found that (1) the proposed method has proven superior in terms of fit and prediction performance than the other models, and (2) unlike other approximations, the proposed model does not detect changes in the rate of extreme rainfall occurrences.


Improvement of Bacillus subtilis Spore Enumeration and Label Analysis in Flow Cytometry.
The spores of Bacillus subtilis have already been proposed for different biotechnological and immunological applications; however, there is an increasing need for the development of methodologies that improve the detection of antigens immobilized on the surface of spores together with their quantification. Flow cytometry-based analyses have been previously proposed as fast, reliable, and specific approaches for detecting labeled cells of B. subtilis. Herein, we propose the use of flow cytometry to evaluate the display efficiency of a fluorescent antibody (FA) on the surface of the spore and quantify the number of spores using counting beads. For this, we used ethidium bromide as a DNA marker and an allophycocyanin (APC)-labeled antibody, which was coupled to the spores, as a surface marker. The quantification of spores was performed using counting beads since this technique demonstrates high accuracy in the detection of cells. The labeled spores were analyzed using a flow cytometer, which confirmed the coupling. As a result, it was demonstrated that DNA labeling improved the accuracy of quantification by flow cytometry, for the detection of germinated spores. It was observed that ethidium bromide was not able to label dormant spores; however, this technique provides a more precise determination of the number of spores with fluorescent protein coupled to their surface, thus helping in the development of studies that focus on the use of spores as a biotechnological platform in different applications.


How and why do toxic conformers of aberrant proteins accumulate during ageing?
Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process.


Transjugular liver biopsy in patients with living donor liver transplantation: comparison with percutaneous biopsy.
Transjugular liver biopsy (TJLB) is an alternative method of pathological diagnosis in patients with an established contraindication to percutaneous biopsy. Between November 2005 and July 2007, 111 TJLBs were attempted in 67 patients and 95 percutaneous liver biopsies (PCLBs) were attempted in 51 patients with living donor liver transplantation suspected of having rejection. Indications of TJLB included classic contraindications to PCLB and a postoperative period of less than 30 days. TJLB was performed a mean of 111.1 +/- 292.6 days after transplantation (range: 6-2478 days, median: 35 days), and PCLB was performed a mean of 534.7 +/- 591.6 days after transplantation (range: 6-2555 days, median: 299 days). Technical success was 99.1% in TJLB and 100% in PCLB, and there was no significant difference between these 2 groups (P = 0.354). A clinical suspicion of rejection was confirmed by histopathology in 38 (34.2%) of 111 TJLBs and 38 (40.0%) of 95 PCLBs. The overall complication rates related to the procedure were 1.8% (2/111) in TJLB and 5.3% (5/95) in PCLB. Although there was no significant difference in complication rates between TJLB and PCLB (P = 0.172), the patients who underwent TJLB showed significantly higher incidence of ascites, coagulopathy, and thrombocytopenia, given its indication. TJLB seems to be a safe and effective procedure for pathological diagnosis of rejection in patients with living donor liver transplantation when there is a high risk of complication with PCLB.


Supplementation with dry Mimosa caesalpiniifolia leaves can reduce the Haemonchus contortus worm burden of goats.
Gastrointestinal nematodes (GINs) cause considerable economic losses in grazing goat herds. At present, GIN control cannot rely on conventional anthelmintic (AH) drugs because parasites have developed resistance against such drugs. Thus, alternative control methods are being sought to reduce the dependence on AH. Many tannin-rich plants exhibit AH activity and may be used as alternatives for GIN control. Mimosa caesalpiniifolia is a tannin-rich shrub consumed by small ruminants in Brazil. This study evaluated the in vivo AH effect of M. caesalpiniifolia leaf powder supplementation on GIN egg fecal excretion and worm burden in goats. Plant leaves were harvested, dried and ground to obtain a powder. Twenty-four castrated male goats, aged six to eight months, with a mean body weight of 15.0 ± 2.5 kg were used in the experiment. Animals were infected orally with 16,000 larvae comprising 50% Haemonchus spp., 41% Trichostrongylus spp. and 9% Oesophagostomum spp. Once the infection was patent, the goats were distributed into four groups of six animals. The control group received concentrate without condensed tannins (CTs) and did not receive any drench against GINs. The monepantel group received concentrate without CTs and were drenched once with monepantel. The other two groups received the M. caesalpiniifolia leaf powder in two periods of seven consecutive days (days 1-7 and 14-21), with one of the groups also receiving 10 g of polyethyleneglycol (PEG)/day. The animals were weighed weekly, and individual fecal eggs counts (FECs) were performed daily. After 28 days, the animals were humanly slaughtered, and the worm burden was estimated. Although live weight gain and FECs did not differ among the groups (P > 0.05), post-mortem worm counts showed a reduction in Haemonchus contortus adult worm burden (57.7%) in goats of the CT group compared to control goats (P < 0.05). The addition of PEG did not diminish AH activity in the CT + PEG group (66.9% reduction compared to the control). No AH effect against other GIN species was found. The result for the addition of PEG suggested that the observed AH activity was associated with plant secondary compounds, as opposed to CTs. As expected, no AH effect against Oesophagostomum columbianum was found for the monepantel group showed. Thus, feeding dry leaves of M. caesalpiniifolia represent a promising alternative for the control of GIN infections in goats.


Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives.
Classic serotonergic psychedelics are remarkable for their capacity to induce reversible alterations in consciousness of the self and the surroundings, mediated by agonism at serotonin 5-HT2A receptors. The subjective effects elicited by dissociative drugs acting as N-methyl-D-aspartate (NMDA) antagonists (e.g. ketamine and phencyclidine) overlap in certain domains with those of serotonergic psychedelics, suggesting some potential similarities in the brain activity patterns induced by both classes of drugs, despite different pharmacological mechanisms of action. We investigated source-localized magnetoencephalography recordings to determine the frequency-specific changes in oscillatory activity and long-range functional coupling that are common to two serotonergic compounds (lysergic acid diethylamide [LSD] and psilocybin) and the NMDA-antagonist ketamine. Administration of the three drugs resulted in widespread and broadband spectral power reductions. We established their similarity by using different pairs of compounds to train and subsequently evaluate multivariate machine learning classifiers. After applying the same methodology to functional connectivity values, we observed a pattern of occipital, parietal and frontal decreases in the low alpha and theta bands that were specific to LSD and psilocybin, as well as decreases in the low beta band common to the three drugs. Our results represent a first effort in the direction of quantifying the similarity of large-scale brain activity patterns induced by drugs of different mechanism of action, confirming the link between changes in theta and alpha oscillations and 5-HT2A agonism, while also revealing the decoupling of activity in the beta band as an effect shared between NMDA antagonists and 5-HT2A agonists. We discuss how these frequency-specific convergences and divergences in the power and functional connectivity of brain oscillations might relate to the overlapping subjective effects of serotonergic psychedelics and glutamatergic dissociative compounds.


Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity.
We investigated the ophthalmic features of a mild form of enhanced S-cone syndrome (ESCS) in a 33-year-old Japanese female proband and 3 unaffected family members. A genetic analysis was performed. Genetic and observational case study. Fundus examinations, optical coherence tomography (OCT), Goldmann visual field (VF) perimetry, color vision tests, spectral sensitivity, and full-field and spectral electroretinography (ERG) were performed. Mutation screening of the NR2E3 gene, which encodes a photoreceptor-specific orphan nuclear receptor, was performed with polymerase chain reaction amplification and direct sequencing. Mutations in the NR2E3 gene, fundus photographs, OCT images, VFs, spectral sensitivity, and ERG findings. The diagnosis of ESCS was made based on the distinctive spectral ERG findings: hypersensitivity to blue stimuli and hyposensitivity to red stimuli. The proband had good visual acuity, normal color vision, good central VFs, and nearly normal spectral sensitivity. Funduscopy showed degenerative lesions in the vascular arcades to the midperipheral retina. The OCT images showed a morphologically normal macular thickness. In the full-field ERG, low amplitudes of rod b-waves were detected. Waveforms between rod-plus-cone and cone ERGs were very similar. Mutation analysis identified 2 novel compound heterozygous missense mutations, p.R104Q and p.R334G, which reside in the DNA-binding domain (DBD) and ligand-binding domain (LBD), respectively. The unaffected parents carried one of these mutations each, consistent with autosomal recessive transmission. Our study suggests that the expression of these 2 mutants of NR2E3, acting as a dimer, is correlated with a mild form of ESCS in that full foveal function and retinal laminar structure are maintained, and certain rod responses are present. This may be explained by the possibility that the heterodimers encoded by the 2 mutant alleles retain certain NR2E3 functions through the respective intact DBD and LBD.


Gender differences in the behavioral associates of loneliness and social dissatisfaction in kindergarten.
Much of the evidence suggesting that loneliness is a risk factor for socio-emotional adjustment difficulties comes from studies with older children and adolescents. Comparatively less is known about the mental health implications of loneliness in early childhood. The goals of the present study were to provide additional convergent validity of the Loneliness and Social Dissatisfaction Questionnaire for Young Children (Cassidy & Asher, 1992) and explore potential gender differences in relations between loneliness and behavior problems in early childhood. A multiple source assessment of 139 kindergarten-aged children (M(age) = 64.76 mos., SD = 4.48) was undertaken, including parental ratings, behavioral observations, child interviews, and teacher ratings. Overall, loneliness was positively associated with anxiety, aggression, and peer exclusion. However, several gender differences were also observed. Loneliness may be a marker variable for both early internalizing and externalizing problems. However, gender differences in the behavioral associates of loneliness are also evident.


Candidemia outcomes not improved with statin use.
Candidemia is an important cause of morbidity and mortality. As statins interfere with yeast membrane synthesis, we assessed whether use of statins during candidemia may cause differences in clinical outcomes. A retrospective review of 124 candidemia episodes during 2003-2008 in which all-cause and attributable mortality, length of stay and level of care were compared for patients who received and those who did not receive statins. A total of 124 candidemia events were observed involving 14 patients on statins and 110 without statins. Overall mortality in candidemia cases was 46%, but only 2% was attributed to candidemia. No differences were observed in clinical outcomes for the two groups of patients. During the last 2-year period of our study, there were higher rates of candidemia caused by non-C. albicans Candida spp., particularly those due to C. glabrata and C. parapsilosis. In conclusion, statin use during candidemia did not alter mortality, length of stay, or intensive care requirement of our patients, despite higher rates of non-C. albicans Candida species isolated during the last 2 years of our study.


Primary epiploic appendagitis: compared with diverticulitis and focused on obesity and recurrence.
There is limited data to compare the clinical characteristics and recurrence rates between left-sided primary epiploic appendagitis (PEA) versus left-sided acute colonic diverticulitis (ACD), and right-sided PEA versus right-sided ACD, respectively. We retrospectively reviewed the medical records and radiologic images of the patients who presented with left-sided or right-sided acute abdominal pain and had computer tomography performed at the time of presentation showing radiological signs of PEA or ACD between January 2004 and December 2014. We compared the clinical characteristics of left PEA versus left ACD and right PEA versus right ACD, respectively. Fifty-six patients (left:right = 27:29) and 308 patients (left:right = 24:284) were diagnosed with symptomatic PEA and ACD, respectively. Left-sided PEA were statistically significantly younger (50.2 ± 15.4 years vs. 62.1 ± 15.8 years, P= 0.009), more obese (body mass index [BMI]: 26.3 ± 2.9 kg/m2 vs. 22.3 ± 3.1 kg/m2 , P< 0.001), and had more tendencies with normal or mildly elevated high-sensitivity C-reactive protein (hsCRP) (1.2 ± 1.3 mg/dL vs. 8.4 ± 7.9 mg/dL, P< 0.001) than patients with left-sided ACD. The discriminative function of age, BMI and CRP between left-sided PEA versus left-sided ACD was 0.71 (cutoff: age ≤ 59 years, sensitivity of 66.7%, specificity of 77.8%), 0.83 (cutoff: BMI > 24.5 kg/m2 , sensitivity of 80.0%, specificity of 80.0%) and 0.80 (cutoff: CRP < 1.8 mg/dL, sensitivity of 72.2%, specificity of 85.7%). If patients with left lower quadrant abdominal pain are less than 60 years, obese (BMI > 24.5 kg/m2 ) with or without normal to mild elevated CRP levels (CRP < 1.8 mg/dL), it might be necessary for clinicians to suspect the diagnosis of PEA rather than ACD.


Genotype v Japanese encephalitis virus is emerging.
Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I-IV. It reveals low similarity between XZ0934 and genotype I-IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic.


Virus incidence in wheat increases under elevated CO2: A 4-year study of yellow dwarf viruses from a free air carbon dioxide facility.
The complexities behind the mechanisms associated with virus-host-vector interactions of vector-transmitted viruses, and their consequences for disease development need to be understood to reduce virus spread and disease severity. Climate has a substantial effect on viruses, vectors, host plants and their interactions. Increased atmospheric carbon dioxide (CO2) is predicted to impact the interactions between them. This study, conducted under ambient and elevated CO2 (550μmolmol-1), in the Australian Grains Free Air Carbon Enrichment facility reports on natural yellow dwarf virus incidence on wheat (including Barley/Cereal yellow dwarf viruses (B/CYDV)). A range of wheat cultivars was tested using tissue blot immunoassay to determine the incidence of four yellow dwarf virus species from 2013 to 2016. In 2013, 2014 and 2016, virus incidence was high, reaching upwards of 50%, while in 2015 it was relatively low, with a maximum incidence of 3%. Across all years and most cultivars, BYDV-PAV was the most prevalent virus species. In the years with high virus incidence, a majority plots with the elevated levels of CO2 (eCO2) were associated with increased levels of virus relative to the plots with ambient CO2. In 2013, 2014 and 2016 the recorded mean percent virus incidence was higher under elevated CO2 when compared to ambient CO2 by 33%, 14% and 34%, respectively. The mechanism behind increased yellow dwarf virus incidence under elevated CO2 is not well understood. Potential factors involved in the higher virus incidence under elevated CO2 conditions are discussed.


Diagnosis of pleuroparenchymal fibroelastosis: A review.
Pleuroparenchymal fibroelastosis (PPFE) is a rare lung disease with unprecedented features characterized by fibroelastotic changes in the subpleural lung parenchyma affecting the upper lobes. PPFE is usually idiopathic, but it can be caused by infection, autoimmunity, bone marrow or lung transplantation, or a genetic predisposition. Histopathologic examination of lung biopsy samples reveals homogenous subpleural fibrosis and abundant elastic fibers, allowing for a definitive diagnosis. As PPFE mimics many interstitial lung diseases, clinicians face significant difficulties in making a definitive final diagnosis. Since most disease-related comorbid conditions manifest at an advanced stage, invasive tissue sampling for histopathologic evaluation is consistently impossible. Such a patient presentation highlights the importance of an analysis based solely on clinical findings, which would provide a definitive diagnosis without the need for a biopsy. Because of its exceptional and inconceivable presentation, PPFE creates a diagnostic dilemma. In light of our two cases and the literature data, we present a diagnostic assessment score assay that relies solely on clinical manifestations without histopathological tissue verification to shed light on the diagnosis of PPFE. This review focuses on PPFE identification through the use of a diagnostic assessment analysis to improve early disease recognition without the use of invasive diagnostic interventions to obtain biopsy samples for histopathologic evaluation. This analytic approach, while not diagnostic in and of itself, may provide a useful pathway for differential diagnosis and may preclude redundant initiatives.


Genetic and Epigenetic Mechanisms Linking Pain and Psychiatric Disorders.
The neurophysiological link between neuropathic pain and depression remains unknown despite evident high comorbidity of these two disorders. However, there is convincing evidence that genotype plays a role in both pain and depression. Using various types of genetic analysis - population genetics, cytogenetics and molecular technologies - specific genes have been implicated in mediating almost all aspects of nociception and mood disorders. The current review attempts to identify specific genes and epigenetic mechanisms common to both disorders. It is concluded that external and internal factors (inflammation, stress, gender, etc.) that contribute to the pathologies may do so through epigenetic mechanisms that may affect expression of these particular genes. The possible involvement of epigenetic regulation in pain and psychiatric disorders suggests that treatments targeting epigenetic mechanisms that mediate adverse life events should be considered.


Treatment of arachnid poisoning in Australia.
Most Australian spiders are capable of causing a bite which produces some degree of local reaction and occasionally systemic effects. However, only the Sydney funnel-web spider which is limited to a 160 kilometre radius from the centre of Sydney and the red-back spider which is found in all States are capable of inflicting a potentially lethal bite.


Non-traumatic chest pain in patients presenting to an urban emergency Department in sub Saharan Africa: a prospective cohort study in Tanzania.
Non-traumatic chest pain (NTCP) is a common reason for emergency department (ED) attendance in high-income countries, with the primary concern focused on life threatening cardiovascular diseases. There is general lack of data on aetiologies, diagnosis and management of NTPC in Sub Sahara African (SSA) countries. We aimed to describe evaluation, diagnosis and outcomes of adult patients presenting with NTCP to an urban ED in Tanzania. This was a prospective observational cohort study of consecutive adult (≥18 years) patients presenting with non-traumatic chest pain to the Emergency Medicine Department (EMD) of Muhimbili National Hospital (MNH) in Dar es salaam from September 2017 to April 2018. Structured case report form was used to collected demographics, clinical presentation, investigations, diagnosis, and EMD disposition and in hospital mortality. We determined frequency of NTCP among our patients, aetiologies, 24-h and 7-day in-hospital mortality, and predictors for mortality. We screened 29,495 adults attending EMD-MNH during the study and 389 (1.3%) presented with NTCP of these, 349 (90%) were enrolled. The median age was 45 (IQR 29-60) years and 177 (50.7%) were female. Overall, 69.1% patients received electrocardiography (ECG) in the EMD and 34.1% had a troponin test. Heart failure and pulmonary tuberculosis (PTB) were the leading hospital diagnoses (12.6% each), followed by chronic kidney disease (10%) and acute coronary syndrome (ACS) (9.6%). Total of 167 (48%) patients were admitted, and the 24-h and 7-day in-hospital mortality were 5 (3%) and 16 (9.6%) respectively. Univariate risk factors for mortality were a Glasgow Coma Scale of < 15 [RR = 3.4 (95%CI 3.2-23)], Acute Coronary Syndrome [RR = 5.7 (95% CI 1.7-11.8) and Troponin > 0.04 ng/ml [RR 2.9 (95%CI 1.2-7.3)]. Features distinguishing cardiovascular from other causes were: bradycardia [RR = 2.6 (95%CI 2.1-3.2)], heart beat awareness [RR = 2.3 (95%CI 1.7-3.2)] and history of diabetic mellitus [RR = 2.2 (95% CI 1.6-3.0)]. In this ED of SSA country, heart failure and pulmonary tuberculosis were the leading causes of NCTP, and ACS was present in 9.6%. NTCP in this setting carries high mortality, and ACS was the leading risk factor for death. ED providers in SSA must increasingly consider cardiovascular causes of NTCP.


PML-IRIS during Fingolimod Diagnosed after Natalizumab Discontinuation.
Background. Natalizumab treatment is frequently discontinued and replaced by alternative medication in multiple sclerosis (MS) patients having a high risk of progressive multifocal leukoencephalopathy (PML). Case Presentation. We report a PML case that was missed on magnetic resonance imaging (MRI) at the time Natalizumab treatment was discontinued. The patient subsequently developed a PML-immune reconstitution inflammatory syndrome after the initiation of Fingolimod treatment, suggesting that immune reconstitution may occur even during Fingolimod induced lymphopenia. Conclusion. This report highlights the need for strict drug surveillance using MRI of Natalizumab-associated MS patients at the time of drug discontinuation and beyond. This is important with respect to pharmacovigilance purposes not only for Natalizumab, but also for alternative drugs used after Natalizumab discontinuation.


[A case of juvenile rheumatoid arthritis with MPO-ANCA associated nephritis].
A 12-year-old girl with a main complaint of sever pain on the both knees was admitted to our hospital in October, 1995. She gave a three year history of recurrent arthralgia and purpuric rashes, and persistent microhematuria and proteinuria. She developed vesicles and purpuric rashes on the hands and auricles, morning stiffness, fever, uveitis and pericarditis. Laboratory findings showed an elevated level of erythrocyte sedimentation rate and iron-deficiency anemia. Serum perinuclear pattern ANCA with antimyeloperioxidase specificity (MPO-ANCA) was positive. A renal biopsy specimen disclosed a focal and segmental necrotizing glomerulonephritis with crescents. Our case fulfills the both diagnostic criteria for polyarteritis nodosa and juvenile rheumatoid arthritis. This is a rare case of MPO-ANCA associated vasculitis in children.


Precise Control over the Rheological Behavior of Associating Stimuli-Responsive Block Copolymer Gels.
"Smart" materials have considerably evolved over the last few years for specific applications. They rely on intelligent macromolecules or (supra-)molecular motifs to adapt their structure and properties in response to external triggers. Here, a supramolecular stimuli-responsive polymer gel is constructed from heterotelechelic double hydrophilic block copolymers that incorporate thermo-responsive sequences. These macromolecular building units are synthesized via a three-step controlled radical copolymerization and then hierarchically assembled to yield coordination micellar hydrogels. The dynamic mechanical properties of this particular class of materials are studied in shear flow and finely tuned via temperature changes. Notably, rheological experiments show that structurally reinforcing the micellar network nodes leads to precise tuning of the viscoelastic response and yield behavior of the material. Hence, they constitute promising candidates for specific applications, such as mechano-sensors.


Simple Endovascular Repair for Symptomatic Aberrant Right Subclavian Artery in a Debilitated Patient.
We report a simple endovascular repair for symptomatic aberrant right subclavian artery (ARSA) in an 11-year-old girl. She had undergone tracheostomy due to hypoxic encephalopathy after cardiac surgery and suffered from dyspnea. Computed tomography revealed tracheal stenosis caused by a vascular ring made with an ARSA and the right common carotid artery. Transcatheter ARSA embolization using an Amplatzer vascular plug and coils was performed. Symptoms improved within a few days after this intervention and no complications such as upper extremity ischemia were encountered. Computed tomography showed the ARSA around the trachea had reduced in size and tracheal stenosis was improved.


Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of Hep 3B cells.
Bufotalin is one of the bufadienolides isolated from Formosan Ch'an Su, which is made of the skin and parotid glands of toads. Ingestion of toad venom results in severe morbidity and high mortality. Although Ch'an Su is clinically toxic, it has been used as an important traditional Chinese medicine for heart failure and pains. In this study, bufotalin-induced apoptosis in human hepatocellular carcinoma Hep 3B cells was investigated. The results indicate that externalization of phosphatidylserine, accumulation of sub-G(1) cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells. The signaling pathway might be via the activation of caspase-8, increase in mitochondrial tBid, disruption of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF). Active caspase-8 might activate caspase-9 and caspase-3 leading to the cleavage of nuclear PARP. Presence of AIF and cleaved PARP in the nuclei might lead to DNA fragmentation. Caspase-8 inhibitor (Z-IETD) or wide-ranging caspase inhibitor (Z-VAD) significantly suppressed the bufotalin-induced apoptosis, while the anti-Fas neutralization antibody had no effect. These data suggest that bufotalin-induced apoptosis in Hep 3B cells might involve caspases and AIF.


Supramolecular and coordination polymer complexes supported by a tripodal tripyridine ligand containing a 1,3,5-triethylbenzene spacer.
By By combining a tripodal tripyridine ligand containing a 1,3,5-triethylbenzene spacer (L) with several divalent transition-metal chlorides, we have selectively prepared a capsule-type supramolecular complex, [PdII3(L)2Cl6] x 2H2O, and one-dimensional (1D) coordination polymer complexes, ([CuII(L)Cl2] x C2H5OH)n, ([CoII3(L)2Cl6] x 2CH2Cl2)n, and ([ZnII3(L)2Cl6] x 2H2O)n, with a zigzag polymer chain, a linear polymer chain, and a ladder polymer chain structure, respectively. All the structures were established in detail by single-crystal X-ray diffraction analysis, and the factors inducing the structural differences among the complexes are discussed by taking account of the differences in coordination geometry (square planar vs tetrahedral) as well as metal-ligand binding strength in the complexes.


Residual effect of defeated stripe rust resistance genes/QTLs in bread wheat against prevalent pathotypes of Puccinia striiformis f. sp. tritici.
The periodic breakdowns of stripe rust resistance due to emergence of new virulent and more aggressive pathotypes of Puccinia striiformis f. sp. tritici have resulted in severe epidemics in India. This necessitates the search for new and more durable resistance sources against stripe rust. The three bread wheat cultivars PBW 343 (carries Yr9 and Yr27), PBW 621 (carries Yr17) and HD 2967 (gene not known) were highly popular among the farmers after their release in 2011. But presently all three cultivars are highly susceptible to stripe rust at seedling as well as at adult plant stages as their resistance has been broken down due to emergence of new pathotypes of the pathogen (110S119, 238S119). In previous study, the crosses of PBW 621 with PBW 343 and HD 2967 and evaluation of further generations (up to F4) against pathotype 78S84 resulted in resistant segregants. In the present study, the F5 and F6 RIL populations have been evaluated against new pathotypes of Pst. The RILs categorized based on the disease severity on the P (Penultimate leaf) and F (flag) leaf into three categories i.e., high, moderate and low level of APR (adult plant resistance) having 1-200, 201-400 and >400 values of AUDPC, respectively, upon infection with stripe rust. The various APR components (latent period, lesion growth rate, spore production and uredial density) were studied on each category, i.e., resistant, moderately resistant and susceptible. The values of APR parameters decreased as the level of resistance increased. Based on molecular analysis, the lines (representing different categories of cross PBW 621 X PBW 343) containing the genes Yr9 and Yr17 due to their interactive effect provide resistance. Based on BSA using 35k SNPs and KASP markers association with phenotypic data of the RIL population (PBW 621 X HD 2967) showed the presence of two QTLs (Q.Pst.pau-6B, Q.Pst.pau-5B) responsible for the residual resistance and two SNPs AX-94891670 and AX-94454107 were found to be associated with the trait of interest on chromosome 6B and 5B respectively. The present study concludes that in the population of both the crosses (PBW 621 X PBW 343 and PBW 621 X HD 2967) major defeated gene contributed towards residual resistance by interacting with minor gene/QTLs.


Interference of nickel with the photosynthetic apparatus of Zea mays.
Photosynthetic capacity of plants in heavy metals-polluted environment depends on growth stage of plants. Previously, Ni effect on the process of photosynthesis was studied in fully developed plants. The objective of our studies was the response of the developing photosynthetic apparatus to Ni. Changes in chlorophyll a fluorescence induction kinetics: t(1/2), F(v), F(m), F(0), F(v)/F(m), the content of chlorophyll a, b and carotenoids (x+c), as well as the ratios of chlorophyll (a+b) to the total carotenoids [(a+b)/(x+c)] and chlorophyll a/b (Chl a/b) were followed in leaves of 3 day old seedlings of Zea mays exposed to 0, 100 and 200 microNi for 8 and 13 days. The values of t(1/2), F(v), F(m) markedly declined in seedlings treated with 200 microM Ni for both periods, while the F(v)/F(m) ratio decreased in those exposed to 200 microM Ni for 13 days. The content of (x+c) declined gradually with time of plant exposure to the metal. The (a+b)/(x+c) ratio was reduced under Ni treatment, particularly after 8 days. The Chl a/b ratio increased in seedlings treated with the metal for 8 days, but decreased after 13-day-exposure, indicating different response of Chl b to Ni depending on the exposure time. During growth under Ni stress maize invested primarily in Cars and the reaction centre pigment-Chl a. The protective mechanisms in the Ni stressed plant are discussed.


A high stability GO nanofiltration membrane preparation by co-deposition and crosslinking polydopamine for rejecting dyes.
In order to improve the stability of nanofiltration membrane in separation and purification, a novel polyelectrolyte multilayer nanofiltration membrane was facilely prepared by co-deposition of polydopamine (PDA) and polyethyleneimine (PEI) on the polyethersulfone (PES) ultrafiltration membrane substrate, followed by immersing graphene oxide (GO) solution, and crosslinking PDA. The modified surfaces were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM), water contact angle, their saline flux and ability to reject salt and dye were determined. The results also exhibited salt rejection ability as Na2SO4 > K2SO4 > MgSO4 > NaCl > KCl > MgCl2, suggesting the higher rejection of divalent anion. Also, the retention order of the dye by the GO modified membrane is DY86 > DB19 > AG27 > DY142 > DB56 > AR151 > VB5, indicating that the GO modified membrane has better rejection of negatively charged dyes as well as higher molecular weight dyes. Ethanol and hypochlorite resistance tests under different pH conditions showed the membranes coated GO enhanced stability in regard to salt rejection properties. Significantly, the anti-biological test confirmed the growth rate of microalgae on the GO introduced membrane was decreased greatly due to enhanced stability and lower roughness.


Implementation and Operational Research: The Effectiveness of Routine Opt-Out HIV Testing for Children in Harare, Zimbabwe.
HIV testing is the entry point to access HIV care. For HIV-infected children who survive infancy undiagnosed, diagnosis usually occurs on presentation to health care services. We investigated the effectiveness of routine opt-out HIV testing (ROOT) compared with conventional opt-in provider-initiated testing and counseling (PITC) for children attending primary care clinics. After an evaluation of PITC services for children aged 6-15 years in 6 primary health care facilities in Harare, Zimbabwe, ROOT was introduced through a combination of interventions. The change in the proportion of eligible children offered and receiving HIV tests, reasons for not testing, and yield of HIV-positive diagnoses were compared between the 2 HIV testing strategies. Adjusted risk ratios for having an HIV test in the ROOT compared with the PITC period were calculated. There were 2831 and 7842 children eligible for HIV testing before and after the introduction of ROOT. The proportion of eligible children offered testing increased from 76% to 93% and test uptake improved from 71% to 95% in the ROOT compared with the PITC period. The yield of HIV diagnoses increased from 2.9% to 4.5%, and a child attending the clinics post intervention had a 1.99 increased adjusted risk (95% CI: 1.85 to 2.14) of receiving an HIV test in the ROOT period compared with the preintervention period. ROOT increased the proportion of children undergoing HIV testing, resulting in an overall increased yield of positive diagnoses, compared with PITC. ROOT provides an effective approach to reduce missed HIV diagnosis in this age group.


Cultivation of cottontail rabbit epidermal (Sf1Ep) cells on microcarrier beads and their use for suspension cultivation of Treponema pallidum subsp. pallidum.
In vitro propagation of Treponema pallidum can be achieved by cocultivation with Sf1Ep cells. This study had two objectives: (i) to achieve suspension cultivation of Sf1Ep cells and (ii) to develop procedures for achieving the replication of T. pallidum in those cell cultures. Seven suspension cultures of Sf1Ep cells yielded an average of 7.2 x 10(8) T. pallidum (36-fold increase) after 12 days.


Lipid-Induced Insulin Resistance in Skeletal Muscle: The Chase for the Culprit Goes from Total Intramuscular Fat to Lipid Intermediates, and Finally to Species of Lipid Intermediates.
The skeletal muscle is the largest organ in the body. It plays a particularly pivotal role in glucose homeostasis, as it can account for up to 40% of the body and for up to 80%-90% of insulin-stimulated glucose disposal. Hence, insulin resistance (IR) in skeletal muscle has been a focus of much research and review. The fact that skeletal muscle IR precedes β-cell dysfunction makes it an ideal target for countering the diabetes epidemic. It is generally accepted that the accumulation of lipids in the skeletal muscle, due to dietary lipid oversupply, is closely linked with IR. Our understanding of this link between intramyocellular lipids (IMCL) and glycemic control has changed over the years. Initially, skeletal muscle IR was related to total IMCL. The inconsistencies in this explanation led to the discovery that particular lipid intermediates are more important than total IMCL. The two most commonly cited lipid intermediates for causing skeletal muscle IR are ceramides and diacylglycerol (DAG) in IMCL. Still, not all cases of IR and dysfunction in glycemic control have shown an increase in either or both of these lipids. In this review, we will summarise the latest research results that, using the lipidomics approach, have elucidated DAG and ceramide species that are involved in skeletal muscle IR in animal models and human subjects.


Electrophysiologic effects of intravenous nicardipine on sinus node function and conduction in humans.
We conducted an intracardiac study of the electrophysiologic effects and kinetics of intravenous nicardipine (N) in 16 patients with or without impaired cardiac conduction, using a randomized, double-blind, crossover design versus placebo (P). N or P were infused intravenously over 5 min: the dose of N was 9.46 +/- 3.85 mg. Standard electrophysiologic parameters of atrioventricular (AV) conduction and sinus function were measured under basal conditions, between 10 and 25 min, and at 65 min, after beginning the first infusion of N or P, and between 10 and 25 min after beginning the second infusion of N or P. Treatment with N significantly reduced systolic (S) and diastolic (D) blood pressure (BP) at 10 min (35 +/- 19 and 25 +/- 17 mm Hg, respectively). N significantly shortened sinus cycle length (SCL), corrected sinus recovery time (CSNRT), AH interval, AV node (AVN) Wenckebach cycle length, and anterograde and retrograde effective (ERPs) and functional refractory periods (FRPs) of the AVN. Infranodal parameters were unaffected. Mean plasma N concentrations at 10 min were 18.5 +/- 7.7 ng/ml/kg and 5.3 +/- 3 ng/ml/kg at 60 min. Two patients experienced slight adverse effects (anginal pain and nausea); another with sick sinus syndrome developed a sinus pause. We conclude that intravenous N affects nodal, but not His conduction, and that it should be administered with care in the presence of SSS.


[Single- and two-layer gradient centrifugation in sperm separation: comparison and appraisal].
To appraise the effect of single- and two-layer Percoll density gradient centrifugation in sperm separation. Twenty semen specimens underwent single-(50%) and two-layer (90% and 45%) density gradient centrifugation, respectively. The sperm class analyzer (SCA) was used to analyze sperm density, motility and dynamic parameters and round cell density before and after the treatment. After separation, the sperm recovery rate of the single-layer method was (65.5 +/- 12.8)%, significantly higher than that of the two-layer method (P < 0.01). The percentages of grade a sperm of the single- and two-layer method were significantly higher than pre-treatment (P < 0.05, P < 0.01), that of the single-layer was significantly lower than that of the two-layer method (P < 0.05), but the percentage of grade c sperm of the former was significantly higher than that of the latter (P < 0.05). Compared with pre-treatment, the percentage of grade a + b sperm of the two-layer method was significantly higher (P < 0.05), while that of the single-layer method showed no significant difference (P > 0.05), and the round cell density of both the methods was significantly lower (P < 0.05, P < 0.01), with no significant differences between the two methods (P > 0.05). The single-layer method yields a higher rate of sperm recovery and causes little change in the sperm motility, while the two-layer method effects a lower rate and significantly improves sperm motility. Both the methods can efficiently separate sperm from round cells, and each has its own advantages and its application value in in vitro treatment of sperm.


Telemedicine portal and standardized clinical documents.
The paper describes the experience of creating a flexible telemedicine portal intended to improve a business process of information exchanges needed to manage real-time telemedicine events. The portal structure allows use of digitally-signed standardized clinical documents based on the HL7 Clinical Document Architecture.


Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.
Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.


Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens.
Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs) and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs), such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.


[Work injuries of 13-17-year-old Icelanders: causes and consequences].
The aim of the research is to investigate work injuries among 13-17-year-old teenagers in Iceland, their causes and seriousness. Firstly, the prevalence of work injuries among the age-group is examined, as is the length of their absence from work, as well as the gender and age differences of both factors. Secondly, the type and the cause of the injuries are investigated. Thirdly, the most serious injuries and their causes are studied further. A survey was carried out amongst 2000 teenagers, aged 13-17, randomly selected from the Registers Iceland. The response rate was 48.4%. The teenagers were asked in a closed question about whether they had had an accident at work, and in an open one about the type and cause of the injury. A Chi-square test was used to test statistical significance: 95% confidence interval (CI). A fifth of the young people had had an accident at work, one quarter of the injured workers were absent from work because of the injury of which 5.9% for more than a week. The percentage of injured workers increases with age and has reached 30,7% among the 17-year-olds. Cuts and sprains were the most common injuries, whereas back injuries and bone fractures caused the longest absences. Sharp instruments were the most common cause of an injury, but lifting/carrying a (heavy) object as well as a fall of an object caused the longest absences. The prevalence of young workers' injuries and the seriousness of some of these injuries are of concern. In addition to education on occupational health and safety (OHS) and OHS training, future research must analyse if their labour market position threaten the young people's safety, and if it is the case, how to prevent it.


Hapten conjugation in the leucocyte migration inhibition test in allergic chromate eczema.
We studied the in vitro conjugation of chromium salts and found that trivalent chromium binds to protein 10 times more strongly than hexavalent chromium. We also investigated the use of two different lymphocyte migration inhibition tests for the diagnosis of chromium allergy. The capillary method proved superior to the Clausen technique, and potassium dichromate was shown to be a better antigen than chromium chloride. The test results correlated well with standard patch tests and we recommend the capillary method for the investigation of difficult cases of suspected chromium allergy.


[A case of pulmonary alveolar proteinosis--evaluation of a Swan-Ganz catheter in bilateral lung lavage].
Lung lavage, known to be effective for alveolar proteinosis, brings about significant hypoxemia immediately after evacuation of lavage fluid. Impeding blood flow of even a distal branch of a pulmonary artery by using a Swan-Ganz catheter (SGC) successfully prevented this hypoxemia. And this SGC procedure could be safely carried out to make lavage of each lung successively in one day.


Perceptions of medical students toward assessors in interprofessional education.
This study aims to establish if medical students think it is fair to be assessed by nursing professors in interprofessional education (IPE) and why. Eighty-seven third-year medical students who participated in the IPE in 2022 submitted self-reflection essays. They were asked how they perceived the assessors, and 86 medical students responded to content analyses. Sixty-seven students (77.9%) agreed to be assessed by nursing professors. They believed that interprofessional assessment is possible because it is an IPE. They also believed that this was an opportunity to be assessed from various perspectives. Nineteen students (22.1%) objected because the assessment criteria may be different and nursing professors would not understand the learning experiences of medical students. Regarding the reasons medical students oppose it, IPE developers should supplement the development of assessment criteria and understand learners' experiences during planning assessment.


Optimization of Online Education and Teaching Evaluation System Based on GA-BP Neural Network.
With the popularization and application of online education in the world, how to evaluate and analyze the classroom teaching effect through scientific methods has become one of the important teaching tasks in colleges. Based on this, this paper studies the application of the GA-BP neural network algorithm. Firstly, it gives a brief overview of the current situation of online education and GA-BP neural network algorithm. Secondly, through the investigation of the online education system in many aspects, it evaluates students' online education classroom teaching quality from five aspects, and this paper proposes a more scientific online education classroom teaching quality evaluation optimization model and finally verifies the reliability of the online education teaching evaluation model through the practice in a university. The results show that the GA-BP neural network-based evaluation optimization model can effectively evaluate the online education in the process of analyzing the quality of online education classroom teaching of most professional students.


Asthma in the elderly: mortality rate and associated risk factors for mortality.
There is a distinct lack of information on the prognosis of asthma in the elderly. In order to compare mortality rates of elderly people with and without asthma and to identify mortality risk factors in those with asthma, 1,233 ambulatory patients aged > or = 65 years with a diagnosis of asthma (n = 210) or chronic nonrespiratory conditions (n = 1,023) were enrolled in a multicentric study. Patients underwent baseline spirometry and multidimensional assessment and were then followed up for a mean of 57.9 months (SD 16.9). We compared mortality rates in the two groups and identified predictors of death using multivariable survival analysis. The 5-year mortality rate in people with asthma was 24.3%, compared to 16.3% in control subjects (p < 0.01), but asthma per se did not explain the excess risk of death. The main causes of death among people with and without asthma were cardiovascular diseases (36.4% and 21.3%, respectively), nonneoplastic lung diseases (28.8% vs 5.4%), and neoplasms (7.6% vs 22.6%). In people without asthma, death was associated with age, gender, smoking, cardiovascular diseases, worse performance on a 6-min walking test, cognitive impairment, depression, and worse respiratory function. In people with asthma, only the association between death and age, smoking, and depression was confirmed. At variance with control subjects, in asthmatics we found an inverse correlation between being overweight and death (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.13 to 0.94) and a trend toward a higher mortality rate in people with a body mass index < 22 kg/m(2) (HR, 2.21; 95% CI, 0.94 to 5.18). Asthma in the elderly was associated with higher mortality rate, although this condition was not an independent risk factor. Causes of death and factors associated with death were somewhat different between people with and without asthma.


Chiasma frequency and distribution in a sample of human males: chromosomes 1, 2, and 9.
Chiasma frequency and the distribution of chiasmata within chromosomes 1, 2, and 9 were investigated in a total of seven males with presumptively normal meiosis. With the exception of one unusual individual there was little variation among the males examined for these characteristics. The exceptional male had a reduced chiasma frequency, which, rather than being considered abnormal, was thought to represent the lower end of the normal range of variability. A statistical analysis of the histograms of chiasma distribution confirmed the impression of overall similarity, and we conclude that genetic maps of these chromosomes may now be constructed without too much disturbance from differences between individuals. The maps will be presented separately in a subsequent paper.


Food system sustainability for health and well-being of Indigenous Peoples.
To describe how Indigenous Peoples understand how to enhance use of their food systems to promote sustainability, as demonstrated in several food-based interventions. Comments contributed by partners from case studies of Indigenous Peoples and their food systems attending an international meeting were implemented with public health interventions at the community level in nine countries. The Rockefeller Foundation Bellagio Conference Center in Bellagio, Italy, where experiences from case studies of Indigenous Peoples were considered and then conducted in their home communities in rural areas. Leaders of the Indigenous Peoples' case studies, their communities and their academic partners. Reported strategies on how to improve use of local food systems in case study communities of Indigenous Peoples. Indigenous Peoples' reflections on their local food systems should be encouraged and acted upon to protect and promote sustainability of the cultures and ecosystems that derive their food systems. Promoting use of local traditional food biodiversity is an essential driver of food system sustainability for Indigenous Peoples, and contributes to global consciousness for protecting food biodiversity and food system sustainability more broadly. Key lessons learned, key messages and good practices for nutrition and public health practitioners and policy makers are given.


Extensive genetic diversity identified among sporadic methicillin-resistant Staphylococcus aureus isolates recovered in Irish hospitals between 2000 and 2012.
Clonal replacement of predominant nosocomial methicillin-resistant Staphylococcus aureus (MRSA) strains has occurred several times in Ireland during the last 4 decades. However, little is known about sporadically occurring MRSA in Irish hospitals or in other countries. Eighty-eight representative pvl-negative sporadic MRSA isolates recovered in Irish hospitals between 2000 and 2012 were investigated. These yielded unusual pulsed-field gel electrophoresis and antibiogram-resistogram typing patterns distinct from those of the predominant nosocomial MRSA clone, ST22-MRSA-IV, during the study period. Isolates were characterized by spa typing and DNA microarray profiling for multilocus sequence type (MLST) clonal complex (CC) and/or sequence type (ST) and SCCmec type assignment, as well as for detection of virulence and antimicrobial resistance genes. Conventional PCR-based SCCmec subtyping was undertaken when necessary. Extensive diversity was detected, including 38 spa types, 13 MLST-CCs (including 18 STs among 62 isolates assigned to STs), and 25 SCCmec types (including 2 possible novel SCCmec elements and 7 possible novel SCCmec subtypes). Fifty-four MLST-spa-SCCmec type combinations were identified. Overall, 68.5% of isolates were assigned to nosocomial lineages, with ST8-t190-MRSA-IID/IIE±SCCM1 predominating (17.4%), followed by CC779/ST779-t878-MRSA-ψSCCmec-SCC-SCCCRISPR (7.6%) and CC22/ST22-t032-MRSA-IVh (5.4%). Community-associated clones, including CC1-t127/t386/t2279-MRSA-IV, CC59-t216-MRSA-V, CC8-t008-MRSA-IVa, and CC5-t002/t242-MRSA-IV/V, and putative animal-associated clones, including CC130-t12399-MRSA-XI, ST8-t064-MRSA-IVa, ST398-t011-MRSA-IVa, and CC6-t701-MRSA-V, were also identified. In total, 53.3% and 47.8% of isolates harbored genes for resistance to two or more classes of antimicrobial agents and two or more mobile genetic element-encoded virulence-associated factors, respectively. Effective ongoing surveillance of sporadic nosocomial MRSA is warranted for early detection of emerging clones and reservoirs of virulence, resistance, and SCCmec genes.


School and work release evaluations.
Increasingly high levels of absenteeism for minor illnesses and injuries have created serious problems for American schools and industries. Short-term absenteeism also creates serious ethical and professional dilemmas for primary care physicians who routinely perform school and work release evaluations. Through an inductive analysis of three typical cases, these problems are identified. The major ethical issues involved are discussed, including truth-telling, confidentiality, and a confusion of the professional boundaries of medicine, education, and industry. Through a deductive analysis, it is shown that the conventional approaches to school and work release evaluations fail to achieve satisfactory results. To circumvent these problems, three solutions are proposed: primary care physicians can refuse to do such evaluations, inform the patient of the purpose and rules of the encounter, or perform evaluations only in the context of treatment.


Otolaryngological manifestations of arthrogryposis multiplex congenita.
The important otolaryngological manifestations of arthrogryposis multiplex congenita (AMC), which heretofore have not been described in otolaryngological and other specialty journals, are reviewed. Thirty-seven patients with AMC were studied. Nine of these patients with neurogenic AMC, had otolaryngological manifestations. Six of these had Pierre Robin-like syndromes. Seven patients had severe dysphagia and aspiration pneumonitis. Five patients had voice changes, and three of these required tracheotomy to relieve laryngeal obstruction and prevent aspiration. Two of these patients were aphonic and had laryngeal paralysis. Three of the nine patients who had laryngeal examination showed supraglottic narrowing similar to laryngomalacia. Six patients with otolaryngological problems were autopsied, and two had pharyngeal biopsies. The histological examination demonstrated normal laryngeal and pharyngeal musculature. The cricoarytenoid joints were found normal in all the larynges examined. Central nervous system dysfunction rather than simple muscle weakness, caused the dysphagia and respiratroy difficulties in patients with neurogenic AMC. Dysphagia with aspiration was the single most important cause of death in approximately 20% of patients with AMC. A tracheotomy and feeding gastrostomy appears essential for successful management of the otolaryngological complications of AMC.


Using DNA-Stable Isotope Probing to Identify MTBE- and TBA-Degrading Microorganisms in Contaminated Groundwater.
Although the anaerobic biodegradation of methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA) has been documented in the laboratory and the field, knowledge of the microorganisms and mechanisms involved is still lacking. In this study, DNA-stable isotope probing (SIP) was used to identify microorganisms involved in anaerobic fuel oxygenate biodegradation in a sulfate-reducing MTBE and TBA plume. Microorganisms were collected in the field using Bio-Sep® beads amended with 13C5-MTBE, 13C1-MTBE (only methoxy carbon labeled), or13C4-TBA. 13C-DNA and 12C-DNA extracted from the Bio-Sep beads were cloned and 16S rRNA gene sequences were used to identify the indigenous microorganisms involved in degrading the methoxy group of MTBE and the tert-butyl group of MTBE and TBA. Results indicated that microorganisms were actively degrading 13C-labeled MTBE and TBA in situ and the 13C was incorporated into their DNA. Several sequences related to known MTBE- and TBA-degraders in the Burkholderiales and the Sphingomonadales orders were detected in all three13C clone libraries and were likely to be primary degraders at the site. Sequences related to sulfate-reducing bacteria and iron-reducers, such as Geobacter and Geothrix, were only detected in the clone libraries where MTBE and TBA were fully labeled with 13C, suggesting that they were involved in processing carbon from the tert-butyl group. Sequences similar to the Pseudomonas genus predominated in the clone library where only the methoxy carbon of MTBE was labeled with 13C. It is likely that members of this genus were secondary degraders cross-feeding on 13C-labeled metabolites such as acetate.


ACTH-independent macronodular adrenocortical hyperplasia (AIMAH): report of two cases and the analysis of steroidogenic activity in adrenal nodules.
We report clinical findings and steroidogenic activities in adrenal tissues in 2 cases of AIMAH. Endocrine studies revealed an undetectable level of plasma ACTH and a diminished circadian rhythm of plasma cortisol. A significant increase in plasma cortisol levels in response to ACTH stimulation was observed in both cases. After the administration of metyrapone in one case, urinary excretion of 17-hydroxycorticosteroid (17-OHCS) significantly increased, although the plasma ACTH level did not respond. Computed tomography showed large masses in both adrenal glands, and bilateral uptake was identified on adrenal scintigraphy. The totals for the bilateral adrenal glands were 98 g and 105 g, respectively, and the left adrenal was larger than the right in both cases. Steroid content in the nodules measured by high performance liquid chromatography (HPLC) showed that the cortisol content was definitely lower than that in cortisol-producing adenoma (CPA) and even in normal adrenals. The activities of cytochrome P450c17, P450c21 and P450c11 were evaluated in one case, and all of them were reduced in the nodules. Especially that of P450c17 was remarkably reduced. These data suggest that cortisol production in AIMAH is inefficient, and that the cause of Cushing's syndrome may be related to the marked increase in the number of cells or bulk of the tumor.


A correlation between thrombotic disease and a specific fibrinogen abnormality (A alpha 554 Arg-->Cys) in two unrelated kindred, Dusart and Chapel Hill III.
For the first time, a correlation between a specific fibrinogen abnormality and the clinical symptoms of thrombosis has been found in unrelated families. These abnormal fibrinogens have been designated Dusart and Chapel Hill III. The abnormal fibrinogen Chapel Hill III was identified previously in a patient with thrombotic disease. We purified fibrinogen from small aliquots of patient and normal plasmas by a simple, rapid procedure. Coomassie stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that fibrinogen Chapel Hill III contained several high molecular weight forms in addition to the two forms seen with normal fibrinogen. Immunoblot analysis of Chapel Hill III fibrinogen demonstrated that essentially all the high molecular weight forms react with antiserum to albumin. Immunoblot analysis of plasmin digests of Chapel Hill III fibrinogen demonstrated that albumin is linked to the C-terminus of the A alpha chain. Using DNA analysis, we found that the patient is heterozygous for a single base change, resulting in the substitution A alpha Arg 554-->Cys. This is the same change identified in fibrinogen Dusart. The Dusart family members who are heterozygous for this substitution also suffer from recurrent thrombotic disorders.


Characterization of post-surgical critical patients with infections associated with healthcare after prolonged perfusion of remifentanil.
Healthcare associated infections (HAI) are the most frequent complication of hospitalized patients. The aim of this study was to describe the clinical and epidemiological characteristics of critically ill post-surgical patients with a diagnosis of healthcare associated infections, after a pattern of sedoanalgesia of at least 4 days. All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology where sedation was based as analgesic the opioid remifentanil for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Data analysis was performed using the statistical package Stata version 7.0. The patients admitted to the Post-Surgical Critical Care Unit (PCU) during study were 1789 and the population eligible was comprised of 102 patients. 56.86% of patients suffered IACS. The most frequent IACS was pneumonia associated with mechanical ventilation (30.96 per 1000 days of mechanical ventilation), Pseudomonas aeruginosa being the most frequently isolated germ. The germs with the greatest involvement in multiple drug resistance (MDROs) were enterobacteria, mainly Klebsiella pneumoniae resistant to extended-spectrum beta-lactamases (ESBL). Pneumonia associated with mechanical ventilation is the most prevalent HAI and Pseudomonas aeruginosa is the main etiological agent. The groups of antibiotics most frequently used were cephalosporin and aminoglycosides. It is necessary to implement the prevention strategies of the different HAI, since most of them are avoidable.


Novel Co2 VO4 Anodes Using Ultralight 3D Metallic Current Collector and Carbon Sandwiched Structures for High-Performance Li-Ion Batteries.
A novel spinel Co2 VO4 is studied as the Li-ion battery anode material and it is sandwiched with a 3D ultralight porous current collector (PCC) and amorphous carbon. Co2 VO4 demonstrates the high capacity and excellent cyclability because of the mixed lithium storage mechanisms. The 3D composite structure requires no binders and replaces the conventional current collector (Cu foil) with a 3D ultralight porous metal scaffold, yielding the high electrode-based capacity. Such a novel composite anode also enables the close adhesion of Co2 VO4 to the PCC scaffold. The resulting monolithic electrode has the rapid electron pathway and stable mechanical properties, which lead to the excellent rate capabilities and cycling properties. At a current density of 1 A g-1 , the PCC and carbon sandwiched Co2 VO4 anode is able to deliver a stable reversible capacity of about 706.8 mAh g-1 after 1000 cycles. Generally, this study not only develops a new Co2 VO4 anode with high capacity and good cyclability, but also demonstrates an alternative approach to improve the electrochemical properties of high capacity anode materials by using ultralight porous metallic current collector instead of heavy copper foil.


Assessment, prevention and treatment of constipation in children.
The management of constipation can often be a challenge in children who may be fearful of opening their bowels and who may be reluctant to sit on the toilet. This article focuses on guidance produced by the National Institute for Health and Clinical Excellence on constipation in children and young people. The guidance discusses successful treatment of constipation, including ensuring effective initial emptying of the bowel and appropriate laxative therapy.


[Long-term efficacy of chemotherapy for unresectable gastric cancer with multiple bone metastases-a case report].
A 49-year-old man was admitted to our hospital with back pain, appetite loss, and body weight loss in January 2009. Gastroduodenal endoscopy, abdominal computed tomography( CT), and magnetic resonance imaging( MRI) revealed type 4 advanced gastric cancer( signet-ring cell carcinoma) with multiple lymph node( No. 16 LNs), right adrenal gland, and multiple bone metastases. Between February 2009 and April 2011, 20 courses of S-1( 80 mg/m2) plus CDDP( 60 mg/m2) and zoledronic acid hydrate (4 mg/body) were administrated. Since May 2011, S-1 (70 mg/m2) and zoledronic acid hydrate( 4 mg/body) have been continued. The lymph node and adrenal gland metastases showed a complete response( CR), and the gastric tumor showed a partial response; however, the bone metastases did not show CR or progressive disease (PD) for 4 years after initiation of therapy. Chemotherapy with zoledronic acid hydrate is considered as a useful therapeutic option for advanced unresectable gastric cancer with multiple bone metastases.


Impaired agonists recruitment during voluntary arm movements in patients affected by spasmodic torticollis.
We have investigated the electromyographic (EMG) and kinematic characteristics of horizontal arm extension movements in patients affected by idiopathic cervical dystonia (ICD) as well as in normal subjects. In spite of the lack of an overt dystonic involvement of the muscles acting at upper arm level, all these patients were considerably bradykinetic. Although the degree of bradykinesia observed was comparable to that previously reported for the body segment directly affected by this patholgy (21,15,8), the EMG analysis of the agonist muscles indicated a specific pathophysiological mechanism. In particular, the recruitment of the posterior deltoid (pD) in ICD patients was severely impaired within the initial phase (130 ms) of the movement. On the other hand, within the same time span, the activation of the mD, a muscle that plays a more important postural role than the pD, was not significantly different between patients and normal subjects. This reduced recruitment in the initial phase of the AG1 appears responsible of the slowness of voluntary movements.


Controlled Sol-Gel Transitions by Actuating Molecular Machine Based Supramolecular Polymers.
The implementation of artificial molecular machines in polymer science is an important objective that challenges chemists and physicists in order to access an entirely new class of smart materials. To design such systems, the amplification of a mechanical actuation from the nanoscale up to a macroscopic response in the bulk material is a central issue. In this article we show that bistable [c2]daisy chain rotaxanes (i.e., molecular muscles) can be linked into main-chain Upy-based supramolecular polymers. We then reveal by an in depth quantitative study that the pH actuation of the mechanically active rotaxane at the nanoscale influences the physical reticulation of the polymer chains by changing the supramolecular behavior of the Upy units. This nanoactuation within the local structure of the main chain polymer results in a mechanically controlled sol-gel transition at the macroscopic level.


Impact of Body Mass Index on Survival of Metastatic Renal Cancer.
Obesity has been established as a risk factor for renal cell carcinoma (RCC). Recently, studies have described obesity as a probable protecting factor in the metastatic stage of RCC. In this study, we assessed the relationship between body mass index (BMI) and overall survival in patients under systemic therapy. The correlation between BMI and overall median survival was studied in 76 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m2) and underweight or normal (BMI < 25 kg/m2). Statistical analysis was performed using the Cox regression model adjusted by gender. A total of 76 patients were studied: 16 women (21%) and 60 men (79%). The median BMI was 27.96 kg/m2; 24 patients (31.6%) had low BMI and 52 (68.4%) had high BMI. Median overall survival in the group with BMI > 25 kg/m2 was 17 months (95% confidence interval [CI]: 13-34 months), while in the group with BMI ≤ 25 kg/m2, it was 14 months (95% CI: 8-20 months). When adjusted by gender, the group with BMI > 25 kg/m2 presented a hazards ratio of 0.54 (95% CI: 0.30-0.96), P = 0.044 (Log Rank). A high BMI significantly acts as a protecting factor. We observed an increased overall survival of overweight and obese patients within the context of metastatic RCC under systemic treatment. These data confirm the findings published in other studies that suggest the role of lipid metabolism in this type of tumors.


Hierarchical Transition-Metal Dichalcogenide Nanosheets for Enhanced Electrocatalytic Hydrogen Evolution.
Hierarchical transition-metal dichalcogenide nanosheets are constructed through a versatile strategy, where the thermal polymerization of melamine and subsequent decomposition of carbon nitride successively guide the horizontal and vertical growths of transition-metal chalcogenides. Abundant edges and high surface areas endow the hierarchical MoS2 and WS2 nanosheets with excellent electrocatalytic performance for hydrogen evolution, including low onset potentials and high current densities.


Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.
Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.


Expression of cyclooxygenase-2 by equine ocular and adnexal squamous cell carcinomas.
To investigate whether cyclooxygenase-2 (COX-2) is expressed by equine ocular and adnexal squamous cell carcinomas (SCC). Forty-three samples of histologically confirmed cases of ocular SCC or carcinoma in situ (CIS) from 34 horses presented to the Animal Health Trust between 1992 and 2004 were subjected to a standard, two-layered, indirect immunohistochemical method using a rabbit polyclonal antihuman COX-2 antibody. Ten formalin-fixed, paraffin-embedded tissue samples taken from recognized predilection sites for SCC, from the grossly normal eyes of 10 horses euthanized for reasons unrelated to this study, were used as negative controls. Samples of equine fetal kidney were used as positive controls. Following immunolabeling, the number of normal and neoplastic epithelial cells exhibiting positive COX-2 expression was recorded along with staining intensity and distribution. Of 43 tumors, 34 were defined as first presentation tumors. When compared with control tissue, in which 0% (0/10) of samples expressed COX-2, significantly more of these samples with SCC (58.6%, 17/29: P = 0.002), CIS (60%, 3/5: P = 0.022) or either tumor type (58.8%, 20/34: P = 0.001) exhibited positive cytoplasmic and perinuclear immunohistochemical staining for COX-2. Of the samples exhibiting positive immunohistochemical staining, only 10% (2/20) showed staining in 2%-10% of neoplastic cells, while 90% (18/20) showed staining in 1% of neoplastic cells. About 70% (14/20) of those positively immunolabeled samples exhibited an intensity of staining greater than or equal to the staining exhibited by the equine fetal kidney positive control. Neoplastic tissue from both equine ocular SCC and CIS exhibit COX-2 expression at significantly higher levels than normal control ocular tissue. However, the percentage of cells expressing positive immunohistochemical staining is consistently low. On the basis of this study, it is unlikely that anti-COX-2 therapy would be of benefit in the treatment of equine ocular and adnexal SCC.


Strategies to improve the bacteriocin protection provided by lactic acid bacteria.
Lactic acid bacteria (LAB) produce a wide variety of antimicrobial peptides (bacteriocins) which contribute to the safety and preservation of fermented foods. This review discusses strategies that have been or could be employed to further enhance the commercial application of bacteriocins and/or bacteriocin-producing LAB for food use.


Seizures in meningioma.
More than one-third of patients with meningiomas will experience seizures at some point in their disease. Despite this, meningioma-associated epilepsy remains significantly understudied, as most investigations focus on tumor progression, extent of resection, and survival. Due to the impact of epilepsy on the patient's quality of life, identifying predictors of preoperative seizures and postoperative seizure freedom is critical. In this chapter, we review previously reported rates and predictors of seizures in meningioma and discuss surgical and medical treatment options. Preoperative epilepsy occurs in approximately 30% of meningioma patients with peritumoral edema on neuroimaging being one of the most significant predictor of seizures. Other associated factors include age <18, male gender, the absence of headache, and non-skull base tumor location. Following tumor resection, approximately 70% of individuals with preoperative epilepsy achieve seizure freedom. Variables associated with persistent seizures include a history of preoperative epilepsy, peritumoral edema, skull base tumor location, tumor progression, and epileptiform discharges on postoperative electroencephalogram. In addition, after surgery, approximately 10% of meningioma patients without preoperative epilepsy experience new seizures. Variables associated with new postoperative seizures include tumor progression, prior radiation exposure, and gross total tumor resection. Both pre- and postoperative meningioma-related seizures are often responsive to antiepileptic drugs (AEDs), although AED prophylaxis in the absence of seizures is not recommended. AED selection is based on current guidelines for treating focal seizures with additional considerations including efficacy in tumor-related epilepsy, toxicities, and potential drug-drug interactions. Continued investigation into medical and surgical strategies for preventing and alleviating epilepsy in meningioma is warranted.