Age-dependent changes in DNA repair in radiation-exposed mice.
Ionizing radiation (IR) is a well-known human carcinogen. Young and adult individuals are known to respond to radiation in a different manner. In this study, we analyzed changes in the spleen of juvenile (two-week-old), adult (two-month-old) and old (18-month-old) C57BL/6 male mice subjected to a whole-body exposure to 1 Gy of X rays. We measured the number of γ-H2AX foci and ATM protein levels as a reflection of the level of DNA double-strand breaks (DSBs), and found that old animals had a high frequency of occurrence of noninduced DSBs. Exposure to X rays resulted in a rapid increase in the number of DSBs in juvenile and adult animals at 6 h postirradiation followed by a return to preirradiated DSB values at 96 h postirradiation. No changes were observed in old animals. The analysis of the levels of proteins involved in DNA damage base excision and mismatch repair pathways, including KU70, RAD51, POL β, POL δ, POL ε, APE1 and MSH2 showed substantial age-dependent radiation-induced differences. Finally, we demonstrated that old animals had a higher background level of cell apoptosis compared to younger animals, but in contrast to younger animals, old animals were not able to commit spleen cells to apoptosis after being irradiated. Thus, spleen cells of old mice have a high level of spontaneous DNA damage, but they are not able to deal with additional radiation-induced damage as efficiently as younger animals, substantiating age-depending differences in radiation-induced DNA damage and repair response and its outcomes.


Randomised controlled trial of analgesic effectiveness of three different techniques of single-shot interscalene brachial plexus block using 20 mL of 0.5% ropivacaine for shoulder arthroscopy.
Shoulder arthroscopic procedures impose a challenge to anaesthesiologists in terms of postoperative analgesia. Proper pain management after arthroscopic procedures improves patient satisfaction and facilitates early rehabilitation. We performed a randomized, prospective clinical study to assess the influence of anthropometric parameters and IBPB technique on the quality of postoperative analgesia. A total of 106 randomly selected patients of ASA I-III status scheduled for elective shoulder arthroscopy. Reasons for exclusion were neurological deficit in the upper arm, allergies to amide-type local anesthetics, coagulopathy, and pregnancy.The patients received 20 mL of 0.5% ropivacaine for an ultrasound-guided interscalene brachial plexus block (IBPB) (group U), peripheral nerve stimulation (PNS)-confirmed IBPB (group N), or ultrasound-guided, PNS-confirmed IBPB (dual guidance; group NU). We observed that the three groups did not differ in mean time of sensory and motor block terminations. In individual cases in each group, sensory block lasted up to 890-990 minutes, providing satisfactory long lasting postoperative analgesia in patients receiving IBPB. We observed a negative correlation between body mass index and termination of motor block (P = 0.037, Pearson's correlation coefficient) and a positive correlation between age and termination of sensory block (P = 0.0314, Pearson's correlation coefficient) in group U compared to the other two groups. We found a positive correlation between male gender and termination of motor block (P = 0.0487, Pearson's correlation coefficient) in group N compared to the other two groups. In our study, patients received satisfactory analgesia in the postoperative period regardless of technique used, age, gender, or potentially uncommon anthropometry.


Effect of Silymarin and Quercetin in a Miniaturized Scaffold in Wistar Rats against Non-alcoholic Fatty Liver Disease.
Silymarin and quercetin (SQ) are known antioxidants with substantial free radical scavenging activities. The efficacy of SQ activity is restricted due to poor absorption and availability. This study aims to increase the hepatoprotective activity of SQ by a newer delivery technique. We have optimized a technique, miniaturized scaffold (MS), for the delivery of active compounds of SQ. SQ molecules were embedded in MS and characterized by morphology, particle size, miniaturization efficiency, and functional group. Further, the hepatoprotective effects of MSQ were investigated through in vitro and in vivo methods. Hepatotoxicity was induced in rats by carbon tetrachloride (CCl4), and subsequently, hepatotoxic rats were treated with the miniaturized scaffold of SQ (MSQ) for 8 weeks. The body weight were significantly high in groups fed with MSQ. A substantial decrease in triglyceride, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase activities were observed in rats treated with MSQ. Similarly, rats treated with MSQ exhibited lower lipid accumulation in the hepatocytes. The experiments clearly demonstrated the efficacy of MSQ as a superior hepatoprotective agent against non-alcoholic fatty liver disease simulated through toxicity induced by CCl4.


Erectile dysfunction and cardiovascular disease.
Erectile dysfunction (ED) is often a comorbid condition commonly associated with cardiovascular disease (CVD). It is important for physicians to understand that the relationship between ED and CVD is not a coincidence but rather a warning signal. The fact that the symptoms of ED normally arise before the symptoms of a cardiovascular event gives physicians the unique opportunity to see the possible future of their patients' cardiovascular health. Vascular disease is the most common cause of ED. This article reviews the incidence of CVD and ED, the pathophysiology of ED, the risk factors associated with ED and CVD, and the evaluation and treatment options for men with ED, and discusses how ED may serve as an early warning for cardiovascular disease.


Artificial intelligence explainability: the technical and ethical dimensions.
In recent years, several new technical methods have been developed to make AI-models more transparent and interpretable. These techniques are often referred to collectively as 'AI explainability' or 'XAI' methods. This paper presents an overview of XAI methods, and links them to stakeholder purposes for seeking an explanation. Because the underlying stakeholder purposes are broadly ethical in nature, we see this analysis as a contribution towards bringing together the technical and ethical dimensions of XAI. We emphasize that use of XAI methods must be linked to explanations of human decisions made during the development life cycle. Situated within that wider accountability framework, our analysis may offer a helpful starting point for designers, safety engineers, service providers and regulators who need to make practical judgements about which XAI methods to employ or to require. This article is part of the theme issue 'Towards symbiotic autonomous systems'.


Parvularia atlantis gen. et sp. nov., a Nucleariid Filose Amoeba (Holomycota, Opisthokonta).
The opisthokonts constitute a eukaryotic supergroup divided into two main clades: the holozoans, which include animals and their unicellular relatives, and the holomycotans, which include fungi, opisthosporidians, and nucleariids. Nucleariids are phagotrophic filose amoebae that phenotypically resemble more their distant holozoan cousins than their holomycotan phylogenetic relatives. Despite their evolutionary interest, the diversity and internal phylogenetic relationships within the nucleariids remain poorly studied. Here, we formally describe and characterize by molecular phylogeny and microscopy observations Parvularia atlantis gen. et sp. nov. (formerly Nuclearia sp. ATCC 50694), and compare its features with those of other nucleariid genera. Parvularia is an amoebal genus characterized by radiating knobbed and branching filopodia. It exhibits prominent vacuoles observable under light microscopy, a cyst-like stage, and completely lacks cilia. P. atlantis possesses one or two nuclei with a central nucleolus, and mitochondria with flat or discoid cristae. These morphological features, although typical of nucleariids, represent a combination of characters different to those of any other described Nuclearia species. Likewise, 18S rRNA-based phylogenetic analyses show that P. atlantis represents a distinct lineage within the nucleariids.


Retroviral vector-mediated overexpression of the RII beta subunit of the cAMP-dependent protein kinase induces differentiation in human leukemia cells and reverts the transformed phenotype of mouse fibroblasts.
We have recently shown, using antisense strategy, that the RII beta regulatory subunit of cAMP-dependent protein kinase is essential for cAMP-induced growth inhibition and differentiation of HL-60 human leukemia cells. We constructed a retroviral vector for RII beta (MT-RII beta) by inserting human RII beta complementary DNA into the OT1521 retroviral vector plasmid that contains an internal mouse metallothionein-1 promoter and a neomycin resistance gene. The PA317 packaging cell line was then transfected with MT-RII beta plasmid to produce the amphotrophic stock of MT-RII beta retroviral vector. The infection with MT-RII beta and treatment with CdCl2 brought about growth arrest in HL-60 human leukemia and Ki-ras-transformed NIH 3T3 clone DT cells in monolayer culture with no sign of toxicity. The growth inhibition correlated with the expression of RII beta and accompanied changes in cell morphology; cells became flat, exhibiting enlarged cytoplasm. The growth of these cells in semisolid medium (anchorage-independent growth) was almost completely suppressed. In contrast, overexpression of the RI alpha subunit of protein kinase enhanced the cell proliferation in DT cells. The MT-RII beta-infected cells exhibited an increased sensitivity toward treatment with cAMP analogues, such as 8-Cl-cAMP and N6-benzyl-cAMP, as compared with the parental noninfected cells. In MT-RII beta HL-60 cells, N6-benzyl-cAMP treatment greatly enhanced the expression of monocytic surface markers. These results suggest that the RII beta cAMP receptor, by binding to its ligand, cAMP, acts as a tumor suppressor protein exerting growth inhibition, differentiation, and reverse transformation.


Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.
Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future.


Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.
This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.


Dual-emitting nanocomposites derived from rare-earth compound nanotubes for ratiometric fluorescence sensing applications.
A new class of ratiometric fluorescence sensors composed of rare-earth (RE) compound nanotubes is described. Polyethylenimine-coated yttrium hydroxide fluoride nanotubes (YHF NTs) that were synthesized hydrothermally exhibit highly efficient fluorescence when doped with RE ions. The polyethylenimine on the NTs facilitates the incorporation of phosphors such as quantum dots or organic dyes onto the NT surface to produce dual-emitting nanocomposites which are excellent ratiometric fluorescence sensors. The phosphor layer and underlying tubes in the nanocomposites act as the indicator and reference probes, respectively. This ratiometric fluorescence method which can be applied to the detection of heavy metals in solutions, temperature sensing, and pH sensing boasts high sensitivity and selectivity as well as better accuracy than traditional intensity-based fluorescence methods.


Effectiveness of the management of major depressive episodes/disorder in adults with comorbid chronic physical diseases: a protocol for a systematic review and meta-analysis.
Depression is a global-scale public health problem, and a significant association has been established between depression and chronic physical diseases. This growing comorbidity poses a challenge to healthcare systems. We aim to assess the effectiveness of the management of major depressive episodes/disorder in adults with comorbid chronic physical diseases. We will conduct a systematic review and meta-analysis of randomised clinical trials. Two databases MEDLINE and Cochrane Library (Cochrane Database for Systematic Reviews and CENTRAL), as well as the reference lists of the included articles, will be searched for studies either in English or Spanish with published results within the 2005-2015 period. Studies must fulfil the following conditions: (1) participants aged 18 years or older, diagnosed as having a major depressive episodes/disorder according to standardised criteria and chronic physical diseases; (2)interventions (be it pharmacological, psychological, psychosocial or a combination) must be compared with control conditions (other 'active' intervention, treatment as usual, waiting list or placebo); (3)and must report reduction in depressive symptoms after treatment, response to treatment, remission of major depressive episodes/disorder and significant improvement in quality of life. Data extraction, risk of bias evaluation, results summarisation and quality of the evidence (GRADE) will be performed as recommended by the Cochrane Collaboration. A qualitative synthesis and a random effects meta-analysis will be carried out. Effect sizes will be calculated (relative risk and Cohen's d), I2 and Q statistics will be employed to study heterogeneity and publication bias analysis will be performed. Subgroup analyses and meta-regression will be carried out. Results are expected to be published in specialised peer-reviewed journals (preferred topics: Mental Health, Psychology, Psychiatry and/or Systematic Reviews) and dissemination activities will be targeted to all the healthcare providers. International Prospective Register of Systematic Reviews (CRD42016029166) submitted on 11 January 2016.


Adverse cutaneous reactions to psychotropic drugs.
This article reviews the adverse cutaneous reactions due to psychotropic medications. The prevalence of skin reactions to these agents is about 5%.


Validation of Algorithms to Identify Invasive Electrophysiology Procedures Using Administrative Data in Ontario, Canada.
Administrative database research can provide insight into the real-world effectiveness of invasive electrophysiology procedures. However, no validated algorithm to identify these procedures within administrative data currently exists. To develop and validate algorithms to identify atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT) catheter ablation procedures, and diagnostic electrophysiology studies (EPS) within administrative data. Algorithms consisting of physician procedural billing codes and their associated most responsible hospital diagnosis codes were used to identify potential AF, AFL, SVT catheter ablation procedures and diagnostic EPS within large administrative databases in Ontario, Canada. The potential procedures were then limited to those performed between October 1, 2011 and March 31, 2013 at a single large regional cardiac center (Sunnybrook Health Sciences Center) in Ontario, Canada. These procedures were compared with a gold-standard cohort of patients known to have undergone invasive electrophysiology procedures during the same time period at the same institution. The sensitivity, specificity, positive and negative predictive values of each algorithm was determined. Algorithms specific to each of AF, AFL, and SVT ablation were associated with a moderate sensitivity (75%-86%), high specificity (95%-98%), positive (95%-98%), and negative (99%) predictive values. The best algorithm to identify diagnostic EPS was less optimal with a sensitivity of 61% and positive predictive value of 88%. Algorithms using a combination of physician procedural billing codes and accompanying most responsible hospital diagnosis may identify catheter ablation procedures within administrative data with a high degree of accuracy. Diagnostic EPS may be identified with reduced accuracy.


Allele specific oligonucleotide analysis of the common deafness mutation 35delG in the connexin 26 (GJB2) gene.
Despite the large number of genes that are expected to be involved in non-syndromal, recessive deafness, only a few have been cloned. One of these genes is GJB2, which encodes connexin 26. A frameshift mutation in this gene has been reported to be common in several populations and a carrier frequency of about 1 in 30 people has been detected in Italy and Spain. Mutation 35delG is difficult to detect because it lies within a stretch of six guanines flanked by thymines, so the deletion of one G does not create or destroy a restriction site and mutagenesis primers are not useful for this mutation. We have generated an allele specific oligonucleotide method that uses 12-mer oligonucleotides and easily discriminates between the normal and 35delG alleles. The method should permit a rapid analysis of this mutation in congenital cases (recessive or sporadic), including diagnosis and carrier detection of 35delG in the population.


Simple regression model using an optode for the simultaneous determination of zinc and cadmium mixtures in aqueous samples.
An optical-fiber chemical sensor (optode) is described for the simultaneous determination of Zn2+ and Cd2+ mixtures using 2-(5-bromo-2-pyridylazo)-5-(diethylamino)phenol immobilized onto XAD-4 (Br-PADAP/XAD-4). A simultaneous analysis was achieved by using a single-wavelength kinetic approach coupled with a regression model. Here, the regression model was derived for the slope response of Br-PADAP/XAD-4 to binary mixtures of the metal ions, Zn2+ and Cd2+, at pH 8. The model was used then to predict the concentration of one metal ion while the other was kept constant. This was found to be reasonably successful for Zn2+ and Cd2+, with deviations of 3% and 10%, respectively. The sensor was also found to provide excellent sensitivity for both metal ions with excellent LODs (< 0.1 ppm) and very short analysis times (< 30 s).


Sequence-dependent force response during peeling of single-stranded DNA from graphite.
We have analyzed the statistical thermodynamics of peeling single-stranded DNA (ssDNA) from the surface of graphite. Using recently measured parameters, we represent ssDNA as a polymer chain strongly adsorbed to a frictionless substrate using the freely jointed chain, wormlike chain, and rotational isomeric state models. All three models predict steady peeling force under force control, in agreement with single-molecule experiments. We predict that, for finite-length chains, the force response has measurable spikes under displacement control. These force spikes carry information about the underlying sequence of ssDNA, which might thus be measurable with a sufficiently stiff loading system. For the freely jointed chain model, under force control, we have obtained several exact closed-form results and provide relations between the measured peel force and the underlying adhesion free energy.


Human corticotropin-releasing hormone during pregnancy.
Elevated irCRH levels up to 14 ng/ml were measured in 176 females in the last trimester. The highest maternal CRH levels were found in those females in whom the period from the onset of labour to full dilatation of the cervix and the time span of delivery were shortest. irCRH in amniotic fluid (120 +/- 180 pg/ml; n = 14) was in the same range as in umbilical cord plasma (233 +/- 188 pg/ml; n = 66) and 20-fold lower than in prepartal maternal plasma (5.38 +/- 4.49 ng/ml; n = 66). irCRH in maternal plasma correlated highly to irCRH in umbilical cord plasma (p less than 0.001; n = 66). After delivery irCRH disappeared from maternal plasma with a half-life of 50 minutes (n = 14). One day postpartum irCRH levels (n = 22) were undetectable. The height of the irCRH levels in the various biological fluids did not correlate to the mode or the pathological events of delivery (n = 43). Maternal ACTH levels above the normal range were encountered only in women immediately prepartal and did not correlate to the CRH levels (253 +/- 229 pg/ml; n = 66). Cortisol levels were higher in maternal plasma than in umbilical cord plasma due to elevated CBG (n = 78). Free cortisol levels were higher in the 3rd trimester than in the 1st (2.18 +/- 0.16 vs 1.16 +/- 0.73 ng/ml; n = 42). irCRH in maternal and umbilical cord plasma correlated to the hPl and estriol levels (p less than 0.001 and p less than 0.05; n = 66). We conclude that irCRH is secreted by the placenta into both maternal and fetal circulation. Though placental CRH is undistinguishable from hypothalamic CRH, the biological significance of placental CRH remains open. Our data show that placental CRH might be responsible for the changed function of the adrenal gland during pregnancy, with higher free cortisol levels in the last trimester. The extremely elevated ACTH levels during labour and delivery indicate that CRH is not the only mediator of stress-induced ACTH secretion in the regulation of the maternal hypothalamo-pituitary-adrenal axis.


Repression of Smad2 and Smad3 transactivating activity by association with a novel splice variant of CCAAT-binding factor C subunit.
Activation by transforming growth factor-beta (TGF-beta)/activin receptors leads to phosphorylation of Smad2 (Sma- and Mad-related protein 2) and Smad3, which function as transcription factors to regulate gene expression. Using the MH2 domain (Mad homologue domain of Smad proteins 2) of Smad3 in a yeast two-hybrid screening, we isolated a novel splice variant of CAATT-binding factor subunit C (CBF-C), designated CBF-Cb, that associated with Smad3. CBF-C is one of the subunits that form a heterotrimeric CBF complex capable of binding and activating the CAATT motif found in the promoters of many eukaryotic genes. CBF-Cb is 62 amino acids shorter than the wild-type CBF-C in the N-terminal region. In addition, CBF-Cb is expressed ubiquitously in various mouse tissues. By an immunoprecipitation assay, we detected an in vivo association of CBF-Cb with Smad2 and Smad3, independent of signalling by activated TGF-beta type I receptors. In transient transfection experiments, overexpression of CBF-Cb was able to repress the transactivating activity of Smad2 and Smad3, mediated either by direct binding to the Smad-responsive element or through their association with the Smad-interacting transcription factor FAST-2 (forkhead activin signal transducer-2). The Smad-mediated transcriptional response after TGF-beta receptor activation was also inhibited by overexpression of unspliced CBF-C. In addition, the repressive activity of CBF-Cb on Smad2- and Smad3-mediated transcriptional regulation was abrogated by co-expression of the general transcription activator p300. The association of CBF-Cb with Smad2 was competitively inhibited by overexpression of p300. These data indicate a novel mechanism for modulation of the transcriptional activity of Smad proteins, whereby the interaction of CBF-Cb, as well as canonical CBF-C, with the MH2 domain of Smads may prevent the association of Smads with transcriptional co-activators.


Effect of suture technique on blood velocity waveforms in the microvascular anastomosis of autogenous vein graft.
In using autogenous vein grafts in microvascular surgery, maintenance of compliance at the site of anastomosis is of importance in achieving patency. Using high-frequency, 20 MHz, pulsed Doppler ultrasonography to monitor blood flow velocity through the vein graft, we have evaluated the effects of continuous and interrupted suture technique on anastomotic compliance in vessels less than 1.5 mm in diameter. In 15 dogs, 15 procedures of each technique, using the continuous technique in one limb and the interrupted technique on the contralateral limb, patency rates for both techniques, documented by arteriography, are 100% at a mean follow-up of 11 weeks. There were no significant differences in the blood velocity profile and pulsatility proximally, distally, and at the graft site between continuous and interrupted technique. This study confirms the suggestion that autogenous vein graft has sufficient elasticity to maintain normal arterial blood velocity waveforms.


Assessing the level of agreement between the self- and interview-administered Child-OIDP.
To assess the level of agreement between the self- and interviewer-administered Child version of the Oral Impacts on Daily Performances (Child-OIDP) index. This was a randomised study in 177 children aged 10-13 years from Granada (Spain). All children completed both administration modes of the Child-OIDP; half the sample received the interviewer-administered version first (n = 90), and the other half the self-administered version first (n = 87). This was done to address potential order effects due to the sequential administration of both instruments. The level of agreement between both modes of administration was assessed with the Bland and Altman method for the Child-OIDP score and Kappa for the prevalence of oral impacts. The two groups did not differ in their socio-demographic characteristics or self-perceived oral health measures. No order effects were found. There was no significant difference between the two modes of administration in terms of the overall score and prevalence of oral impacts (P > or = 0.784 in both cases). The mean difference in Child-OIDP scores was 0.03 (95% CI = -0.29 to 0.35) and the 95% limits of agreement were -6.32 and 4.93. Kappa value for the prevalence of impacts was 0.92. The self- and interviewer-administered Child-OIDP had a high level of agreement, irrespectively of whether the overall score or the prevalence of oral impacts was used to describe children's quality of life.


Effects of Universal Adhesive on Shear Bond Strength of Resin Cement to Zirconia Ceramic with Different Surface Treatments.
This study aimed to assess shear bond strength (SBS) of resin cement to zirconia ceramic with different surface treatments by using Single Bond Universal. In this in vitro study, 50 zirconia discs (2 × 6 mm) were divided into 5 groups of (I) sandblasting with silica-coated alumina (CoJet) + silane + Single Bond 2, (II) sandblasting with CoJet + Single Bond Universal, (III) sandblasting with alumina + Single Bond Universal, (IV) sandblasting with alumina + Z-Prime Plus, and (V) Single Bond Universal with no surface treatment. Resin cement was applied in plastic tubes (3 × 5 mm2), and after 10,000 thermal cycles, the SBS was measured by a universal testing machine. The mode of failure was determined under a stereomicroscope at × 40 magnification. Data were analyzed using one-way ANOVA. The maximum (6.56 ± 4.29 MPa) and minimum (1.94 ± 1.96 MPa) SBS values were noted in groups III and I, respectively. Group III had the highest frequency of mixed failure (60%). Group V had the maximum frequency of adhesive failure (100%). Single Bond Universal + sandblasting with alumina or silica-coated alumina particles is an acceptable method to provide a strong SBS between resin cement and zirconia.


Toward the neural mechanisms of reduced working memory capacity in schizophrenia.
People with schizophrenia (PSZ) demonstrate reliable reductions in working memory (WM) capacity (i.e., the number of objects that can be held in memory). The present study asked whether WM impairments in PSZ can be explained by the same neural mechanisms that underlie individual differences in WM capacity among healthy individuals. Specifically, we examined event-related potentials in PSZ and healthy matched controls during a change detection task that required the storage of multiple objects in WM. The amplitude of contralateral delay activity (CDA), which correlates with WM capacity in healthy individuals, was larger in controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than in controls for a memory load of 1. This same pattern was found in the subgroups of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA amplitude was correlated with individual differences in capacity in controls, but not in PSZ. These results demonstrate that WM impairment in PSZ is not associated with the same patterns of neural activity that characterize low WM capacity in healthy individuals. We propose that WM impairment in PSZ instead reflects a specific impairment in the ability to distribute attention broadly.


Stem cell factor-induced bone marrow mast cell hyperplasia mimicking systemic mastocytosis (SM): histopathologic and morphologic evaluation with special reference to recently established SM-criteria.
Although systemic mastocytosis (SM) is a well-defined hematologic neoplasm, it is sometimes difficult to discriminate between SM and a reactive mast cell (MC) hyperplasia. We describe a patient with aplastic anemia who was treated with recombinant stem cell factor (SCF). In response to SCF, the patient showed transient hematologic improvement and developed a marked increase in MC as well as a transient increase in serum tryptase. Histologic and immunohistochemical examination revealed a huge increase in MC in the bone marrow with focal infiltrates similar to SM. However, most of the SM-criteria were not met: First, MC showed normal cytomorphological characteristics without significant atypias (no cytoplasmic extensions, no oval nuclei, no hypogranulated cytoplasm). Furthermore, bone marrow MC were CD2- and CD25-negative and did not exhibit the C-KIT 2468 A-->T mutation (Asp-816-Val). After discontinuation of SCF the MC hyperplasia resolved confirming its reactive nature. Based on our case and similar cases mimicking mastocytosis, it seems of importance to apply recently established SM criteria in order to discriminate between reactive MC hyperplasia and true mastocytosis with certainty.


Slow-release synthesis of Cu single-atom catalysts with the optimized geometric structure and density of state distribution for Fenton-like catalysis.
Single-atom Fenton-like catalysis has attracted significant attention, yet the quest for controllable synthesis of single-atom catalysts (SACs) with modulation of electron configuration is driven by the current disadvantages of poor activity, low selectivity, narrow pH range, and ambiguous structure-performance relationship. Herein, we devised an innovative strategy, the slow-release synthesis, to fabricate superior Cu SACs by facilitating the dynamic equilibrium between metal precursor supply and anchoring site formation. In this strategy, the dynamics of anchoring site formation, metal precursor release, and their binding reaction kinetics were regulated. Bolstered by harmoniously aligned dynamics, the selective and specific monatomic binding reactions were ensured to refine controllable SACs synthesis with well-defined structure-reactivity relationship. A copious quantity of monatomic dispersed metal became deposited on the C3N4/montmorillonite (MMT) interface and surface with accessible exposure due to the convenient mass transfer within ordered MMT. The slow-release effect facilitated the generation of targeted high-quality sites by equilibrating the supply and demand of the metal precursor and anchoring site and improved the utilization ratio of metal precursors. An excellent Fenton-like reactivity for contaminant degradation was achieved by the Cu1/C3N4/MMT with diminished toxic Cu liberation. Also, the selective ·OH-mediated reaction mechanism was elucidated. Our findings provide a strategy for regulating the intractable anchoring events and optimizing the microenvironment of the monatomic metal center to synthesize superior SACs.


Motivation for eating behaviour in adolescent girls: the body beautiful.
Body dissatisfaction is commonplace for teenage girls and is associated with dieting and unhealthy weight-control behaviours. The idealisation and pursuit of thinness are seen as the main drivers of body dissatisfaction, with the media prominent in setting thin body ideals. Television and consumer magazine production in the UK are extensive, annually releasing 1x10(6) h programming and >3000 magazine titles. Their engagement by adolescent girls is high, and in surveys girls identify thin and revealing body images as influential to the appeal of thinness and their pursuit of dieting. Experimental studies show a short-term impact of these images on body dissatisfaction, especially in teenagers who are already concerned about body image. Magazine images appear more influential than television viewing. For many adolescents selecting thin-image media is purposive, permitting comparison of themselves with the models or celebrities featured. Indeed, the impact of the media needs to be understood within a social context, as engagement is often a highly-social process. Media influence is uneven because of differences in its content and manner of communication, and individual differences in vulnerability to its content. Greater social responsibility on the part of the media and better media literacy by children would be beneficial. For those working in adolescent nutrition it is a reminder that adolescent food choice and intake are subject to many competing, contradictory and non-health-related determinants.


Venous thromboembolism does not share strong familial susceptibility with coronary heart disease: a nationwide family study in Sweden.
This nationwide study aimed to determine whether venous thromboembolism (VTE) shares familial susceptibility with coronary heart disease (CHD). Data from the Swedish Multigeneration Register for subjects aged 0-76 years old for the period 1964-2008 were linked to the Hospital Discharge Register and Cause of Death Register. Familial risks of VTE and CHD were examined in two ways: risk of CHD in offspring whose parents had been diagnosed with VTE, and risk of VTE in offspring whose parents had been diagnosed with CHD. The analyses were repeated separately for siblings and spouses. In total, 174 768 offspring had CHD and 56 302 VTE. No association between VTE and CHD was observed among siblings. Among offspring, a lower risk of CHD was observed in subjects whose parents had suffered from VTE [standardized incidence ratio (SIR) 0.94 (95% confidence interval (CI) 0.92-0.95)], while offspring of parents with CHD had an increased risk of VTE [SIR 1.03 (95% CI 1.01-1.04)]. In spouses of VTE patients, an increased risk of CHD was observed [SIR 1.02 (95% CI 1.01-1.03)]. Conversely, risk of VTE was increased among spouses of CHD patients [SIR 1.03 (95% CI 1.02-1.03)]. Subanalyses of cases of myocardial infarction and pulmonary embolism/deep venous thrombosis showed similar results. The familial background of CHD is different from that of VTE. The present study suggests that it is unlikely that shared disease-causing mutations exist to a large extent in the population.


Cell uptake of paclitaxel solid lipid nanoparticles modified by cell-penetrating peptides in A549 cells.
The aim of this study was to investigate the cytotoxicity of paclitaxel solid lipid nanoparticles (SLN) modified with stearic acid octaarginine (SA-R8-PTX-SLN) as well as the cellular uptake of coumarin-6-loaded SLN modified with SA-R8 (SA-R8-C6-SLN) in human lung cancer cells, A549. SLN were prepared using a film dispersion method; and then their particle size, zeta potential, morphology, bound efficiency of SAR8, drug loading efficiency, and in vitro release were characterized. SA-R8-PTX-SLN and SA-R8-C6-SLN were incubated with A549 cells to measure their cytotoxicity and cellular uptake, respectively. The results indicated that the cytotoxicity of SA-R8-PTX-SLN was enhanced significantly with the increasing amount of SA-R8 and the cellular uptakes of SLN increased with the incubated concentrations and the incubated time of SLN. In contrast, SA-R8-SLN could significantly enhance the cellular uptake of SLN and the cytotoxicity of PTX in A549 cells. These in vitro results suggest that SA-R8-SLN could be proposed as alternative drug delivery system.


A rare case of paraovarian cancer coexisting with cancer of the fallopian tube: magnetic resonance appearance.
Primary paraovarian cancer is a rare tumor occurring in the female pelvis. Magnetic resonance imaging features of paraovarian cancer have not been previously reported. In the present report, we describe a case of paraovarian cancer coexisting with cancer of the fallopian tube and the magnetic resonance features.


Acute-on-chronic liver failure: management and prognosis.
Hospitalizations due to complications of cirrhosis continue to rise. Patients with chronic liver disease who suffer acute decompensation [acute-on-chronic liver failure (ACLF)] often require intensive care support and are at high risk for short-term mortality. Given the high mortality rate associated with this condition is incumbent on intensive care providers who care for this patient population to have a working knowledge of ACLF with its associated complications, management strategies and prognosis. Recognizing ACLF as a distinct clinical entity has gained international attention in recent years though a consensus does not exist. There has been progress on better defining this clinical entity and recent studies have begun to address the critical care needs of these patients. Additional studies are required to define the best care practices for patients with ACLF. ACLF is a condition occurring in patients with chronic liver disease which is commonly associated with a need for intensive care support and carries a high risk of short-term mortality. Intensive care specialists must be familiar with diagnosis and management of this condition.


[Acquired pathology of the hip in children].
Hip pathology is a frequent motive for consultation in the field of paediatrics. The clinical examination and the radio-imagery both play a central role in the diagnostic process. If acute benign synovitis is the principal cause in the child, it remains a diagnosis of exclusion and must not in any case lead to a missed diagnosis of septic arthritis. Other diagnoses should be evoked according to the age of the child: epiphysiolysis, true surgical emergency, primary osteochondritis of the hip, early inflammatory polyarthritidies.


Eptacog Alfa (Activated) Is Physically and Chemically Stable over 24 Hours when Administered as Bolus Injections in an Automated Infusion Pump.
Introduction Eptacog alfa (activated) is a recombinant activated factor VII (rFVIIa) used for the treatment and prevention of bleeding episodes in patients with congenital hemophilia with inhibitors. Frequent dosing requirements make the use of an automated bolus infusion pump a promising alternative to manual administration. Aims The objective of this in vitro study was to evaluate the physical and chemical stability of room temperature-stable rFVIIa at 25°C over 24 hours in an automated bolus infusion pump. Methods An automated bolus infusion pump with preset bolus injection intervals of 2 to 6 hours was used. Samples of rFVIIa were analyzed for critical quality parameters, presence of leachables, and microbiological growth. The infusion system was evaluated visually. Results rFVIIa is physically and chemically stable when used in an automated bolus infusion pump system for up to 24 hours at 25°C. All critical quality parameter results were within the shelf-life limits and complied with the acceptance criteria. Leachables were observed at concentrations within their respective acceptance criteria. No visual changes in the syringe or infusion tube were observed; inherent particles in the reconstituted rFVIIa similar in size and description to those previously found in rFVIIa were seen. No microbiological growth was detected. Conclusions rFVIIa is stable in a bolus infusion pump system for up to 24 hours at 25°C. Bolus injection intervals of 2 to 6 hours can be used without physical or chemical changes to rFVIIa. This study supports the use of an automated bolus infusion pump in the hospital setting, across all indications for rFVIIa.


Quantitative Analysis of Six Phenolic Acids in Artemisia capillaris (Yinchen) by HPLC-DAD and Their Transformation Pathways in Decoction Preparation Process.
We aimed to establish a quantitative analysis method of six constituents (5-caffeoylquinic acid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid) in Artemisia capillaris (Yinchen) and its decoction by using HPLC coupled with DAD. Besides, the transformation paths of the six constituents were analyzed in decoction preparation processing. The analytical method was fully validated in terms of linearity, sensitivity, precision, repeatability, and recovery and applied to assess the transformation trend and quantitative analysis of the six constituents in Yinchen decoction. The contents of six constituents varied greatly in Yinchen herb and Yinchen decoction, and there were inextricable internal relationships between them. Presumably 3-caffeoylquinic acid was isomerized to generate 5-caffeoylquinic acid and 4-caffeoylquinic acid. Similarly, 1,3-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid were produced by isomerization of 4,5-dicaffeoylquinic acid. In conclusion, this study provides a chemical basis for quality control of Yinchen decoction, and the changes of selected markers in decoction could give us some novel perspectives to study the relationship between substances and drug efficacy.


Synthesis and in-vitro antibacterial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-1,4-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylates.
A series of N-nicotinoyl-1-ethyl-6-fluoro-1,4-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylates has been synthesized and evaluated for antibacterial activity. Norfloxacin was reacted with thionyl chloride, to yield norfloxacin acid chloride which was used immediately in next step by reacting with respective alcohols to furnish the corresponding esters i.e. 1-ethyl-6-fluoro-1,4-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylates (III). Nicotinoyl chloride (IV) was prepared by adopting reported procedures and was reacted appropriately with previously synthesized esters (III) to yield the title compounds (V). The structures of synthesized compounds were established on the basis of analytical and spectral studies. All the synthesized compounds were evaluated for antibacterial activity against four different strains of bacteria. Compounds exhibited moderate to significant minimum inhibitory concentration (MIC) values ranging from 0.19 to 0.37 against E. coli, 0.17 to 0.37 against S. dysentry. The MIC values against Gram positive bacteria were slightly more that Gram negative ones and ranged from 1.9 to 3.5 against S. aureus and 2.0 to 3.1 against B. subtilis.


DTL reconciliation repair.
Maximum parsimony phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of hosts and parasites, genes and species, and other interdependent pairs. Since the problem of finding temporally feasible maximum parsimony reconciliations is NP-complete, current methods use either exact algorithms with exponential worst-case running time or heuristics that do not guarantee optimal solutions. We offer an efficient new approach that begins with a potentially infeasible maximum parsimony reconciliation and iteratively "repairs" it until it becomes temporally feasible. In a non-trivial number of cases, this approach finds solutions that are better than those found by the widely-used Jane heuristic.


Efficient biotechnological approach for lentiviral transduction of induced pluripotent stem cells.
Induced pluripotent stem (iPS) cells are generated from differentiated adult somatic cells by reprogramming them. Unlimited self-renewal, and the potential to differentiate into any cell type, make iPS cells very promising candidates for basic and clinical research. Furthermore, iPS cells can be genetically manipulated for use as therapeutic tools. DNA can be introduced into iPS cells, using lentiviral vectors, which represent a helpful choice for efficient transduction and stable integration of transgenes. In this study, we compare two methods of lentiviral transduction of iPS cells, namely, the suspension method and the hanging drop method. In contrast to the conventional suspension method, in the hanging drop method, embryoid body (EB) formation and transduction occur concurrently. The iPS cells were cultured to form EBs, and then transduced with lentiviruses, using the conventional suspension method and the hanging drop method, to express miR-128 and green fluorescent protein (GFP). The number of transduced cells were assessed by fluorescent microscopy and flow cytometry. MTT assay and real-time PCR were performed to determine the cell viability and transgene expression, respectively. Morphologically, GFP+ cells were more detectable in the hanging drop method, and this finding was quantified by flow cytometric analysis. According to the results of the MTT assay, cell viability was considerably higher in the hanging drop method, and real-time PCR represented a higher relative expression of miR-128 in the iPS cells introduced with lentiviruses in drops. Altogether, it seems that lentiviral transduction of challenging iPS cells using the hanging drop method offers a suitable and sufficient strategy in their gene transfer, with less toxicity than the conventional suspension method.


Ab initio multiple cloning simulations of pyrrole photodissociation: TKER spectra and velocity map imaging.
We report a detailed computational simulation of the photodissociation of pyrrole using the ab initio Multiple Cloning (AIMC) method implemented within MOLPRO. The efficiency of the AIMC implementation, employing train basis sets, linear approximation for matrix elements, and Ehrenfest configuration cloning, allows us to accumulate significant statistics. We calculate and analyze the total kinetic energy release (TKER) spectrum and Velocity Map Imaging (VMI) of pyrrole and compare the results directly with experimental measurements. Both the TKER spectrum and the structure of the velocity map image (VMI) are well reproduced. Previously, it has been assumed that the isotropic component of the VMI arises from long time statistical dissociation. Instead, our simulations suggest that ultrafast dynamics contributes significantly to both low and high energy portions of the TKER spectrum.


Deciphering bloody imprints through chemical enhancement.
Obliterated bloody impressions are occasionally submitted to the crime laboratory, and potentially to the document examiner, for decipherment. Nondestructive methods often lead to inconclusive results in these circumstances. With this point in mind, the researchers explored a series of chemical reagents with the intent to enhance bloody imprints to a legible degree. The reagents selected for this comparison include rhodamine dye, luminol, and Coomassie Blue stain.


Determinants of the magnitude of socioeconomic inequalities in mortality: A study of 17 European countries.
The magnitude of socioeconomic inequalities in mortality differs importantly between countries, but these variations have not been satisfactorily explained. We explored the role of behavioral and structural determinants of these variations, by using a dataset covering 17 European countries in the period 1970-2010, and by conducting multilevel multivariate regression analyses. Our results suggest that between-country variations in inequalities in current mortality can partly be understood from variations in inequalities in smoking, excessive alcohol consumption, and poverty. Also, countries with higher national income, higher quality of government, higher social transfers, higher health care expenditure and more self-expression values have smaller inequalities in mortality. Finally, trends in behavioral risk factors, particularly smoking and excessive alcohol consumption, appear to partly explain variations in inequalities in mortality trends. This study shows that analyses of variations in health inequalities between countries can help to identify entry-points for policy.


Mode of inheritance and evidence for cistron heterogeneity of chloroplast 16S ribosomal RNA genes in Nicotiana.
Oligonucleotide maps (fingerprints) of T1 RNase digests of 125I-labeled 16 S chloroplast rRNA of Nicotiana tabacum and N. gossei revealed the presence of T1 oligonucleotide fragment 100 in the 16 S rRNA of N. gossei while N. tabacum 16 S rRNA had a unique T1 oligonucleotide (fragment 101) as well as some fragment 100. From the positions in the fingerprints and from fingerprints of secondary enzymatic digestion of the fragments, we conclude that fragments 100 and 101 are similar in sequence and size, but fragment 100 probably contains an extra uracil residue. This difference is shown to be maternally inherited, thus confirming the location of 16 S chloroplast rRNA genes on chloroplast DNA and ruling out the possibility of genetically active chloroplast rRNA genes in the nucleus. The presence of both fragments 100 and 101 in N. tabacum may indicate sequence heterogeneity between the two cistrons for 16 S chloroplast rRNA. These results demonstrate the feasibility of determining the inheritance of organelle genes by genetic analysis of their primary transcripts.


[Empirical research of measuring elderly health utility in the outskirts of Beijing by using European quality of life 5-dimensions].
To evaluate health utility values of the elderly in the outskirts of Beijing by European quality of life 5-dimensions (EQ-5D) from the EuroQol Group, and to compare the health utility values by using different translation models. In the cross-sectional study, EQ-5D was used to measure the quality of life for 65 to 79 year-old usual residents in the town of Qinglonghu and Zhoukoudian in Fangshan District of Beijing. The health index which represented the health utility was calculated by using the Japan, the United Kingdom (UK), the United States (US) population-based time trade-off (TTO) models. Kruskal-Wallis H test was adopted to compare the health indexes calculated by the different models, and intraclass correlations coefficients (ICCs) and Bland-Altman plot were used to evaluate the consistency of the utility calculated by the three models. Mann-Whitney U test was used to compare the impacts of Cardio-vascular diseasel (CVD) on the 3 kinds of health index. The Spearman rho correlation coefficients between the 3 kinds of health index, EQ-VAS (visual analogue scales) score and age, gender, health status were also calculated. There were 2 406 participants in this analysis, with a mean age of 70.3 years, of whom 34.3% were male. The median and quantile range of Japan weights, US weights and UK weights health indexes were 1 (0.28), 1 (0.24) and 1 (0.29), respectively. The minimum and maximum of the three indexes were -0.06/1, -0.43/1 and -0.03/1, respectively. The US weights yielded the highest scores and the UK weights the lowest scores. The Japan, US and UK weight scores differed from each other (P<0.005). The Japan and US scores had the highest ICCs (0.987, 95%CI 0.986-0.988), followed by the US and UK scores (0.941, 95%CI 0.937- 0.946) and then the Japan and UK scores (0.921, 95%CI 0.915-0.927). The difference scores of 96.9%, 95.1% and 95.0% were found between the limits of agreement in Bland-Altmand plot. Negative correlations existed between the US/UK score and the number of CVDs, but not existed between the Japan score and the number of CVDs. The health indexes calculated by using the different EQ-5D TTO transform models were different for the elderly people in the Beijing suburban district, TTO model based on Chinese health preference should be developed.


[Review on the neuroprotective effects of green tea polyphenols for the treatment of neurodegenerative diseases].
Considering the multi-etiological characters of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the diseases. Green tea polyphenols have been reported to possess more than two active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in neurodegeneration. This review aims to shed light on the multipharmacological neuroprotective activities and the mechanisms of green tea polyphenols on neurodegenerative diseases.


Estimating good discrete partitions from observed data: symbolic false nearest neighbors.
A symbolic analysis of observed time series requires a discrete partition of a continuous state space containing the dynamics. A particular kind of partition, called "generating," preserves all deterministic dynamical information in the symbolic representation, but such partitions are not obvious beyond one dimension. Existing methods to find them require significant knowledge of the dynamical evolution operator. We introduce a statistic and algorithm to refine empirical partitions for symbolic state reconstruction. This method optimizes an essential property of a generating partition, avoiding topological degeneracies, by minimizing the number of "symbolic false nearest neighbors." It requires only the observed time series and is sensible even in the presence of noise when no truly generating partition is possible.


Women survivors of intimate partner violence: the difficult transition to independence.
Objective To understand the trajectories that women go through from entering into to leaving relationships involving intimate partner violence (IPV), and identify the stages of the transition process. Method We utilized a constructivist paradigm based on grounded theory. We ensured that the ethical guidelines of the World Health Organization for research on domestic violence were followed. The analysis focused on narratives of 28 women survivors of IPV, obtained from in-depth interviews. Results The results showed that the trajectories experienced by women were marked by gender issues, (self) silencing, hope and suffering, which continued after the end of the IPV. Conclusion The transition process consists of four stages: entry - falls in love and becomes trapped; maintenance - silences own self, consents and remains in the relationship; decides to leave - faces the problems and struggles to be rescued; (re) balance - (re) finds herself with a new life. This (long) process was developed by wanting (and being able to have) self-determination.


In situ mechanical interferometry of matrigel films.
Many biological materials and cell substrates are very soft (Young's modulus <500 Pa) and it is difficult to characterize their mechanical properties. Here we report local elasticity of the surface layers of Matrigel films used for cell culture. We used a new measurement technology, mechanical imaging interferometry, to obtain point mechanical measurements over micron-sized areas. The median values of 650 +/- 400 Pa (# measurements, n = 50), determined by the Hertz contact model, agree well with bulk measurements; however, on the microscale, the films were heterogeneous and contained regions distinctly stiffer than average (1-2 kPa). The first measurement of yield strengths of 170 +/- 100 Pa (n = 43) indicates that Matrigel films deform plastically at stress levels of similar scale to cell tractional forces.


The Association Between Inflammatory and Oxidative Stress Biomarkers and Plasma Metabolites in a Longitudinal Study of Healthy Male Welders.
Human metabolism and inflammation are closely related modulators of homeostasis and immunity. Metabolic profiling is a useful tool to understand the association between metabolism and inflammation at a systemic level. To investigate the longitudinal associations between the concentration of plasma metabolites and biomarkers related to inflammation and oxidative stress. We conducted a repeated cross-sectional analysis consisting of 8 short-term panels that included 88 healthy adult male welders in Massachusetts, USA. In each panel, we collected 1-6 repeated measurements of blood and urine. We used a human vascular injury panel assay and custom cytokine/chemokine assay to quantify inflammatory biomarker plasma levels, liquid chromatography-mass spectrometry to quantify the concentrations of 665 plasma metabolites, and a competitive enzyme-linked immunoassay to quantify urinary 8-OHdG and 8-isoprostane levels. We used linear mixed effects models to estimate the longitudinal association between each inflammatory and oxidative stress biomarker and each metabolite. At a 5% FDR threshold, we detected ≥1metabolite association for 8 unique inflammatory and oxidative stress biomarkers: urinary 8-isoprostane, plasma C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1, circulating vascular cell adhesion molecule-1, interleukin 8 (IL-8), interleukin 10 (IL-10) and vascular endothelial growth factor. Specifically, 3 metabolites in the androgenic steroids pathway were negatively associated with SAA; 3 dihydrosphingomyelins metabolites were positively associated with 1 or more of CRP, SAA, IL-8 and IL-10; 4 metabolites in acyl choline metabolism pathways were negatively associated with IL-8; 7 lysophospholipid metabolites were negatively associated with 1 or more of CRP, SAA and IL-8; 4 sphingomyelins were positively associated with CRP and/or SAA; and 10 metabolites in the xanthine pathway were positively associated with urinary 8-isoprostane. We found that metabolites in phospholipid groups had strong associations with multiple inflammatory biomarkers, especially CRP, SAA and IL-8. The mechanism of these associations warrants further investigation.


Ovarian Cancer in the Elderly: Time to Move towards a More Logical Approach to Improve Prognosis-A Study from the FRANCOGYN Group.
Elderly and/or frail women with ovarian cancer are often undertreated. The aim of the study is to compare the effects of age and frailty on surgical approaches, postoperative complications, and prognosis in elderly women with ovarian cancer. A retrospective multicenter study of women ≥70 years were treated for ovarian cancer at seven French university hospitals between 2007 and 2015. Of the 1119 women treated for ovarian cancer during the study period, 147 were ≥70 years and had complete data. Of these women, 65 were aged 70-74 years, and 82 were aged ≥75 years. Overall, 77% of the younger women (49/65) received optimal treatment compared with 51% (40/82) of the older women (p = 0.018). Women ≥75 years underwent fewer bowel resections (32% vs. 67%, p < 0.001) and experienced fewer postoperative complications (22.6% vs. 38.9%, p < 0.001); 53.2% of the women in this age group were treated by primary surgery or surgery only. These women also received more chemotherapy with platinum only (15% [9/56] vs. 2% [1/57], p = 0.007) and less bevacizumab (9% [5/56] vs. 32% [18/57], p = 0.003). Patients with greater frailty (a modified Charlson Comorbidity Index [mCCI] score >3) had a five-year survival rate of 30% versus 62% for those with a score ≤3 (p < 0.001). Surgeons modify their approach to treating ovarian cancer in women ≥75 years probably to reduce immediate postoperative complications. The prognosis is significantly worse in patients with greater frailty. Improvements to the sequence of treatments administered, with priority given to neoadjuvant chemotherapy in patients with greater frailty, could help increase the number of women who receive optimal treatment and improve their prognosis.


First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.
New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents.


Viability and Composition Validation of Commercial Probiotic Products by Selective Culturing Combined with Next-Generation Sequencing.
The consumption of dietary supplements to treat health complications or to improve overall health conditions has become a globally increasing trend that leads to the development of a large number of health-related novel products and expands the associated manufacturing industries around the world. In the current study, we applied selective culturing combined with next-generation sequencing to examine the microbial viability in terms of its culturability on culture medium, composition, and possible contamination in the selected 17 commercial probiotic products sold in the mainland China market. Additionally, the relative abundance of each individual bacterial content was also evaluated by using the generated sequencing reads. The tested probiotic product samples were subjected to Illumina HiSeq-2000 sequencing platform and thoroughly analyzed by the in-house developed bioinformatics pipeline. The comprehensive culturing and sequencing analysis revealed both viability and composition inaccuracy among the several tested probiotic products, however, no contaminant was identified during the analysis. Among the total, five probiotic products (29.41%) were found with an inaccurate or lower colony-forming unit (CFU) counts on culture media while four probiotic products (23.52%) have inaccurately labeled classification. This study provides an ideal qualitative and quantitative assessment approach, which can be used as a diagnostic tool for the accurate assessment of commercial probiotic supplements.


Radical versus Functional Endoscopic Sinus Surgery for Osteitis in Chronic Rhinosinusitis.
Osteitis in chronic rhinosinusitis (CRS) is a predictive factor of disease severity and an important potential reason for disease recalcitrance. Other than medical treatment, transnasal endoscopic surgery could be another choice to deal with osteitis in CRS. In this study, 2 different surgical outcomes and influence in patients with osteitis in CRS were discussed. A retrospective analysis of 51 cases was carried out. Osteitis in CRS was confirmed by sinus computed tomography (CT). According to surgical management, patients were divided into the radical endoscopic sinus surgery (RESS) group (n = 24) and functional endoscopic sinus surgery (FESS) group (n = 27). Baseline measures and postoperative outcomes were evaluated by symptom visual analog scale (VAS), peripheral blood eosinophil percentage, serum total IgE, skin prick test, endoscopy Lund-Kennedy score, CT scan Lund-Mackay score, and global osteitis scoring scale (GOSS) in 2 groups. There was no significant difference between the 2 groups in age, gender, and complicated with allergic rhinitis and asthma. The preoperative symptom VAS score and endoscopy Lund-Kennedy score were higher in the RESS group than in the FESS group, and the Lund-Mackay score and GOSS score were similar in the 2 groups. One year after surgery, symptom VAS scores, endoscopy Lund-Kennedy score, and Lund-Mackay score were significantly lower in the 2 groups. The endoscopy Lund-Kennedy score and Lund-Mackay score were lower in the RESS group than in the FESS group 1 year after surgery. RESS was more effective in reducing inflammatory load of sinuses in patients with osteitis in CRS.


Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor.
The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the existence of many other HIV-1 coreceptors. To investigate the physiologic function of CCR5 and to understand the cellular mechanisms of these clinical observations, we generated a CCR5-deficient mouse model (ccr5[-/-]) by targeted deletion of the ccr5 gene. We found that although developed normally in a pathogen-free environment, CCR5-deficient mice showed reduced efficiency in clearance of Listeria infection and exert a protective effect against LPS-induced endotoxemia, reflecting a partial defect in macrophage function. In addition, CCR5-deficient mice had an enhanced delayed-type hypersensitivity reaction and increased humoral responses to T cell-dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating T cell-dependent immune response.


The status of occupational safety among health service providers in hospitals in Tanzania.
Occupational hazards exist wherever health care is practised. However, there is dearth of information on the status of occupational safety among hospital workers in Tanzania. This study was therefore carried to assess the current status of occupational health and safety (OHS) in Tanzanian hospitals and identify key areas for intervention. Data was collected using a self-administered questionnaire randomly distributed to the health service providers (HSPs) working in 14 district, regional and referral hospitals in Tanzania. A total of 430 HSPs (mean age = 42+/-8.8 years) were involved in the study. Female workers accounted for the majority (71%) of the respondents. None of the 430 respondents had received training on OHS as a profession. Most of the supervisors were holders of certificates (54.4%). Only 42.9% (6/14) of the hospitals, had at least a supervisor with post-graduate degree. Needlestick injuries accounted for the largest part of the most common accidents (52.9%); followed by splash of blood from patients (21.7%); burn injury from chemicals (10.6%); and slippery floors (5.9%). There was lack of qualified personnel for OHS in all hospitals. Most of the hazardous activities were carried out by nurses and attendants. Chemicals used in hospitals were mainly antiseptics and disinfectants, which causes skin burns during handling and use. Seminars and workshops were the major source (N = 429; 33%) of information on OHS. The seven major hazardous activities were injection, cleaning, patient care, bedding, dressing of wounds, medication and surgical operation. The largest proportion of HSPs involved in hazardous activities was found at referral hospitals. The mostly available antiseptics were 70-90% alcohol, 3% aqueous iodine, chlorhexidine gluconate and cetrimide. In conclusion, the OHS was observed to be inadequate in most workplaces in Tanzanian hospitals. Special efforts including training, exposure to information and creation of awareness, are recommended for improving occupational health and safety in hospitals in Tanzania.


Chick integrin alpha V subunit molecular analysis reveals high conservation of structural domains and association with multiple beta subunits in embryo fibroblasts.
We have cloned and characterized a chick homologue of the human vitronectin receptor alpha subunit (alpha v) whose primary sequence is 83% identical with its human counterpart but less than 40% identical with any other known integrin alpha subunit. Comparison of the chick and human sequences reveals several highly conserved regions, including the cytoplasmic domain. The putative ligand binding domain contains alpha v-specific residues that may contribute to ligand binding specificity. These are concentrated in three regions that are located before and between the first three Ca2+ binding domains. Polyclonal antibodies raised against two peptides deduced from the putative cytoplasmic and extracellular domains of the chick alpha v sequence recognize specifically integrin heterodimers in chick embryo fibroblasts. At least three putative beta subunits coimmunoprecipitate with the chick alpha v subunit. In addition to a protein with the same molecular weight as beta 3 (94K), protein bands of Mr 84K and 110K are also coprecipitated. By successive immunodepletions, we demonstrate that this latter Mr 110K subunit is beta 1, which appears to be one of the alpha v-associated subunits in chick embryo fibroblasts.


Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine.
To compare pain-related treatment satisfaction, patient-perceived side effects, functioning, and well-being in patients with advanced cancer who were receiving either transdermal fentanyl (Duragesic, Janssen Pharmaceuticals, Titusville, NJ) or sustained-release oral forms of morphine (MS Contin, Perdue Frederick Co, Norwalk, CT, or Oramorph SR, Roxanne Laboratories, Columbus, OH). A total of 504 assessable cancer patients participated in this cross-sectional, quality-of-life study. Relevant elements of four validated scales were used--the Functional Assessment of Cancer Therapy-General (FACT-G) scale, the Brief Pain Inventory (BPI), the Medical Outcomes Study (MOS) questionnaire, and the Memorial Symptom Assessment Scale (MSAS)--as well as original scales that were developed and validated for this study. The majority of patients in both treatment groups had late-stage (IV/D) cancer. Patients who received transdermal fentanyl were more satisfied overall with their pain medication than those who received sustained-release oral forms of morphine (P = .035). Fentanyl patients also experienced a significantly lower frequency (P < .002) and impact (P < .001) of pain medication side effects. These results occurred despite the fact that cancer patients who received fentanyl were significantly older (P < .001) and had significantly lower functioning and well-being scores (P = .001). Measures of pain intensity, sleep adequacy, and symptoms demonstrated no significant differences between treatment groups. These data suggest that patients are more satisfied with transdermal fentanyl compared with sustained-release oral forms of morphine. A lower frequency and reduced impact of side effects with transdermal fentanyl may be one reason cancer patients who receive fentanyl are more satisfied with their pain management.


The effect of water on the microstructure of 1-butyl-3-methylimidazolium tetrafluoroborate/TX-100/benzene ionic liquid microemulsions.
The ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) forms nonaqueous microemulsions with benzene with the aid of nonionic surfactant TX-100. The phase diagram of the ternary system was prepared, and the microstructures of the microemulsion were recognized. On the basis of the phase diagram, a series of ionic liquid-in-oil (IL/O) microemulsions were chosen and characterized by dynamic light scattering (DLS), which shows a similar swelling behavior to typical water-in-oil (W/O) microemulsions. The existence of IL pools in the IL/O microemulsion was confirmed by UV/Vis spectroscopic analysis with CoCl2 and methylene blue (MB) as the absorption probes. A constant polarity of the IL pool is observed, even if small amounts of water are added to the microemulsion, thus suggesting that the water molecules are solubilized in the polar outer shell of the microemulsion, as confirmed by FTIR spectra. 1H NMR spectroscopic analysis shows that these water molecules interact with the electronegative oxygen atoms of the oxyethylene (OE) units of TX-100 through hydrogen-bonding interactions, and the electronegative oxygen atoms of the water molecules attract the electropositive imidazolium rings of [bmim][BF4]. Hence, the water molecules are like a glue that stick the IL and OE units more tightly together and thus make the microemulsion system more stable. Considering the unique solubilization behavior of added water molecules, the IL/O microemulsion system may be used as a medium to prepare porous or hollow nanomaterials by hydrolysis reactions.


Screening for placental insufficiency by transvaginal uterine artery Doppler at 22-24 weeks of gestation.
To determine the value of routine transvaginal color Doppler assessment of the uterine arteries at 22-24 weeks of gestation in the prediction of placental insufficiency. Women with singleton pregnancies scheduled for routine ultrasound scans at 22-24 weeks were offered Doppler assessment of the uterine arteries by transvaginal ultrasound. The pulsatility index (PI) was obtained for each artery and the mean value was calculated. A mean PI >95th percentile was considered increased. Screening characteristics for predicting placental insufficiency, defined as preeclampsia, fetal growth restriction or intrauterine death, were calculated. Doppler examination of the uterine arteries was carried out in 1,057 singleton pregnancies. The mean uterine artery PI was 1.03 and the 95th percentile was 1.55. In 54 cases (5.1%) the mean PI was >1.55 (screen-positive). In the study population there were 48 cases of preeclampsia (5.1%), 72 fetal growth restrictions (7.5%) and 7 intrauterine deaths (0.7%). The screen-positive group showed an incidence of 47.1% of combined adverse results. The relative risks after a positive screening test were 7.3 (CI 4.2-12.6) for pre-eclampsia, 3.9 (CI 2.3 - 6.6) for fetal growth restriction and 4.5 (CI 3.2-6.4) for overall placental insufficiency. Uterine artery Doppler at 22-24 weeks identifies women at higher risk for the development of subsequent complications of placental insufficiency. This test could be used in combination with other markers to stratify the level of care offered in the third trimester of pregnancy.


Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid utilization regulator.
How bacterial response to environmental cues and nutritional sources may be integrated in enabling host colonization is poorly understood. Exploiting a reporter-based screen, we discovered that overexpression of Mycobacterium tuberculosis (Mtb) lipid utilization regulators altered Mtb acidic pH response dampening by low environmental potassium (K+). Transcriptional analyses unveiled amplification of Mtb response to acidic pH in the presence of cholesterol, a major carbon source for Mtb during infection, and vice versa. Strikingly, deletion of the putative lipid regulator mce3R resulted in loss of augmentation of (i) cholesterol response at acidic pH, and (ii) low [K+] response by cholesterol, with minimal effect on Mtb response to each signal individually. Finally, the ∆mce3R mutant was attenuated for colonization in a murine model that recapitulates lesions with lipid-rich foamy macrophages. These findings reveal critical coordination between bacterial response to environmental and nutritional cues, and establish Mce3R as a crucial integrator of this process.


Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer.
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines. Immunohistochemical analysis of the tissue micro array derived from these patients established the functional correlation between the decreased expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR, EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the patients with extended progression-free survival (PFS) ( > 21 months) versus the patients with the PFS of < 21 months indicated increased expression of tumor suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS patients. In addition to defining a specific set of miRNAs and their target genes as potential diagnostic biomarkers, our studies have identified tumor suppressive miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy response in endometrial cancer.


[The Brugada Syndrome in a Teenager].
The Brugada syndrome (BS) belongs to the group of hereditary channelopathies associated with elevated risk of sudden death (SD) in the absence of structural heart diseases. The disorder phenotypically manifests by specific electrocardiographic pattern, associated with ventricular tachycardia (VT). VT can be accompanied by loss of conscience, and after transformation to ventricular fibrillation result in SD. BS is extremely rare among children and adolescents. We present here a clinical case of teenager (age 17 years) with BS manifested by syncopal state at the background of fever.


The amino acid sequence of the glycosylated amyloid immunoglobulin light chain protein AL MS.
The authors report on the amino acid sequence of the glycosylated amyloid protein AL MS. The amyloid fibrils were extracted from the spleen of a patient (MS.) with amyloidosis. The protein AL MS was purified from the amyloid fibrils by gel filtration. SDS-PAGE performed on the purified protein material showed glycosylated protein bands in the range of 22 to 32 kDa, corresponding to polymerization of N-terminal fragments. The protein was characterized by amino acid analysis and Edman degradation. Tryptic digest combined with Staphylococcal V8 protease, chymotrypsin and pyroglutamate aminopeptidase digestion, as well as cleavage with BNPS-skatole, established the complete amino acid sequence of 168 residues. The protein was compared to other proteins in the SWISSPROT databank, showing homology with the immunoglobulin light chain variable subgroup lamda I. AL MS showed some unique amino acid substitutions. Highly conserved residues Gly(57) and Arg(61), were exchanged to arginine and glutamine, respectively, possibly altering the three- dimensional structure of the protein.


Effects of variations in pH and hypothiocyanite concentrations on S. mutans glucose metabolism.
Hypothiocyanous acid (HOSCN) and hypothiocyanite (OSCN-) were generated by the antibody-independent salivary peroxidase (SP) system. The metabolism of Streptococcus mutans NCTC 10449 was examined by uniformly labeled glucose incorporation studies. We found that the SP-system causes a pH-dependent inhibition of 14C-labeled glucose uptake, and that the effects of HOSCN/OSCN- are bacteriostatic. The results also showed that, at low pH, bacteria required more time to recover fully from HOSCN/OSCN- inhibition. When control experiments were performed in the absence of HOSCN/OSCN-, but the pH was varied, we found a positive correlation between pH and the rate of 14C-glucose incorporation. The results also showed that pH did not affect the maximum incorporation of 14C-glucose, demonstrating that S. mutans can adapt to pH changes in the environment. Based on the data obtained, we postulate that the antibody-independent SP system plays an important role in the regulation of the metabolism of oral streptococci.


Thyroid hormone insufficiency during brain development reduces parvalbumin immunoreactivity and inhibitory function in the hippocampus.
Thyroid hormones are necessary for brain development. gamma-Amino-butyric acid (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in brain, many of which contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe postnatal hypothyroidism reduces PV immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal serum T(4) by approximately 50-75% and increased TSH. At weaning, T(4) was reduced by approximately 70% in offspring in the low-dose group and fell below detectable levels in high-dose animals. PV-IR was diminished in the hippocampus and neocortex of offspring killed on postnatal d 21, an effect that could be reversed by postnatal administration of T(4). Dose-dependent decreases in the density of PV-IR neurons were observed in neocortex and hippocampus, with the dentate gyrus showing the most severe reductions (50-75% below control counts). Altered staining persisted to adulthood despite the return of thyroid hormones to control levels. Developmental cross-fostering and adult-onset deprivation studies revealed that early postnatal hormone insufficiency was required for an alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions in paired pulse depression indicative of a suppression of GABA-mediated inhibition. These data demonstrate that moderate degrees of thyroid hormone insufficiency during the early postnatal period permanently alters interneuron expression of PV and compromises inhibitory function in the hippocampus.


Dramatic effect of dispersed carbon nanotubes on the mechanical and electroconductive properties of polymers derived from ionic liquids.
Free-radical polymerization of an imidazolium ion-based ionic liquid bearing a methacrylate group, gelling with single-walled carbon nanotubes (SWNTs), allows fabrication of a mechanically reinforced, electroconductive soft material (bucky plastic). A film sample of this material displays an excellent conductivity of 1 S cm(-1) and a 120-fold enhancement of the Young's modulus at a 7 wt % content of SWNTs. The conductivity is temperature-dependent in the range 5-300 K, suggesting that the conductive process involves carrier hopping. Scanning electron and atomic force micrographs of a bucky plastic film display the presence of crosslinked networks consisting of finely dispersed SWNTs. Such nanotube networks, developed in the polymer matrix, likely suppress slipping of entrapped polymer molecules via a strong interfacial interaction and also facilitate intertubular carrier transport. Although a bucky plastic derived from a vinylimidazolium ion-based ionic liquid monomer shows a comparable conductivity to that of the methacrylate version, the film is brittle irrespective of the presence or absence of SWNTs.


[Occupational cancers: notification, compensation and prevention].
Less than 140 occupational cancers (OC) are compensated every year in France although the incidence is estimated for at least 6,000 new cases, as estimated by the epidemiologists (4% of the mortality by cancers). This situation can be explained by different factors: few compensation claims by the patients or families, frequent lack of interest from medical doctors for relation between cancer and work, occurrence of the OC after retirement, difficulty to distinguish the role of occupational factors from individual comportmental factors in many OC (for ex. a lung cancer hitting a smoker). The consequences of such a situation are multiple: no compensation for more than 95% of patients or relatives, taking for granted that OC is a minor problem, insufficient prevention of the carcinogenic factors on the work place, prevention of cancers restricted to individual comportmental changes. Physicians working in cancerology units have to incite their patients in notifying the OC and help them in compensation claims. They have also to ask for epidemiologic and toxicologic research when clusters of OC are identified in a plant, in order to get better prevention, compensation and regulations.


To evaluate the serum cortisol, salivary cortisol, and serum interleukin-1 B level in patients of chronic periodontitis with smoking and stress and without smoking and stress.
The role of cognitive, social and biological factors in the etiology of chronic periodontitis has been reported.The aim of this study was to evaluate the salivary cortisol level and interleukin-1 B level in patients of Chronic periodontitis in smokers and stress and nonsmokers without stress.The design of study randomized, prospective, double-blinded, and prospective study.The total sample size was comprised of 600 subjects between the ages of 20 and 50 years. The sample size was divided into 300 males and 300 females. Out of 600 subjects, 200 subjects comprised of subjects with chronic periodontitis with positive depression level with a history of smoking (Group I), 200 subjects comprised of subjects with chronic periodontitis without depression and without smoking (Group II), and 200 subjects who were taken as the control group comprised of healthy subjects without chronic periodontitis, without depression level, and no smoking history (Group III). Salivary cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA).The result showed that there was a positive correlation between morning and evening salivary cortisol level in all the groups with correlation coefficient. There was significant higher value of salivary cortisol in Group I patients when compared with Group II and Group III. However, when the comparison of salivary cortisol levels was done between the Group II and Control group, the result showed nonsignificant P value.It is suggested that stress is positively correlated with the salivary cortisol levels in smokers and nonsmokers.


Clustering and spatial heterogeneity of bovine tuberculosis at the livestock/wildlife interface areas in Namwala District of Zambia.
Bovine tuberculosis (bTB) remains a major public health issue in Zambia and has been exacerbated by human immunodeficiency virus prevalence and consumption of unpasteurized milk in the Southern Province of the country. The prevalence of bTB has been established to be linked to Kafue Lechwe, which act as reservoir hosts and share grazing fields with domestic cattle. No studies have so far used geographic information system (GIS) to investigate the relationship between the reservoir hosts (Kafue Lechwe) and domestic animals. This study, therefore, aimed to apply GIS to investigate the spatial distribution of bTB in Namwala District of the Southern Province of the country. To investigate the spatial distribution of bTB, geographical positioning system (GPS) coordinates representing 96 cattle herds across 20 independent villages were captured alongside risk factor data. The 96 herds were based on abattoir reports of condemned carcasses and a trace back. Positive herds were confirmed by cross-reference to purified protein derivative tests conducted by the District Veterinary Office. The GPS coordinates were transferred into ArcView 3.2 and laid on the map of Namwala District alongside physical features, including national parks, game management areas, and flood plains. Questionnaires were administered across 96 independent households to assess risk factors of bTB transmission. The results revealed a "clustered" spatial distribution of the disease in cattle in Namwala District of Zambia, particularly significant in the eastern interface areas of the district (p=0.006 using Moran's I). Abattoir to production area trace back revealed a herd-level prevalence of 36.4% (95% CI=26.7-46.3%) among cattle herds in Namwala District, whereas individual animal prevalence ranged from 0% to 14% (95% CI=2.4-26.2%). Further, GPS data indicated that the majority of the positive herds were located at the livestock/wildlife interface area. Contacts with wildlife, coupled with sharing grazing, and watering points were found to be significant risk factors for bTB transmission. This study demonstrated the presence of bTB in cattle and associated spatial risk factors. In particular, bTB was observed to be a function of animal location within the livestock/wildlife interface area. GIS is thus an applicable and important tool in studying disease distribution.


The prognostic role of the preoperative platelet to lymphocyte ratio in laryngeal cancer.
Background: In recent years, several studies have investigated the relationship between platelet to lymphocyte ratio (PLR) and the prognosis of patients with laryngeal cancer, but the results remain controversial. This study aimed to evaluate the prognostic significance of pretreatment PLR in patients with laryngeal cancer. Methods: Up to July 2023, we searched PubMed, PubMed Central, Web of Science, Embase, CNKI and Wanfang databases to collect relevant articles evaluating the relationship between PLR and the prognosis of laryngeal cancer. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using the random effect-model. Results: A total of 14 included studies involving 3220 patients with laryngeal cancer were included. The combined results suggested that elevated PLR was associated with poorer overall survival (HR = 2.21, 95% CI, 1.67 - 2.93, p < 0.001), progression-free survival (HR = 2.54, 95% CI, 1.76-3.66, p < 0.001), recurrence-free survival (HR = 1.87, 95% CI,1.45 - 2.42, p < 0.001), and disease-free survival (HR = 1.46, 95% CI, 1.08-1.98, p < 0.001). Subgroup analysis further confirmed that pretreatment PLR was an independent predictor of OS in laryngeal cancer patients. Conclusion: Higher pretreatment PLR is strongly related to poor prognosis of laryngeal cancer patients. This indicates that PLR has the potential to serve as a valuable biomarker for predicting the prognosis of laryngeal cancer. However, further validations in large prospective cohorts are necessary to confirm its clinical utility and reliability.


Differentiation of malignant and benign musculoskeletal tumors: combined color and power Doppler US and spectral wave analysis.
To assess the use of combined color Doppler ultrasonography (US), power Doppler US, and spectral wave analysis (SWA) in differentiating malignant and benign musculoskeletal tumors. Seventy-nine musculoskeletal tumors (34 malignant, 45 benign) were examined with color and power Doppler US and SWA. Two radiologists independently assessed US images and SWA findings. Echotexture and vessel characteristics such as stenoses, occlusions, loops, shunts, trifurcations, vascular pattern, and resistive index were evaluated. All tumors were subject to US-guided or open biopsy for histologic correlation. Combined color and power Doppler US and SWA revealed four major (stenosis, occlusion, trifurcation, vascular pattern) and three minor (shunt, self loop, resistive index) vessel characteristics, which proved helpful in differentiating benign from malignant lesions. Echotexture showed moderate sensitivity (82% [28 of 34 tumors]) and low specificity (38% [17 of 45 tumors]). When comparing several combinations of vessel characteristics, a combination of any two major characteristics demonstrated the best results (sensitivity, 94% [33 of 39 tumors]; specificity, 93% [three of 45 tumors]). Combining more than two characteristics resulted in lower sensitivity. Combined color and power Doppler US and SWA may enable assessment of vascular architecture and altered flow of musculoskeletal tumors. Vascular architecture analysis enables differentiation of benign and malignant lesions and evaluation of musculoskeletal tumors.


Exploring the Relationship Between Auditory Brainstem Response Testing and Disease Progression in Pediatric Autism Spectrum Disorder.
This study aimed to examine auditory brainstem response (ABR) test results in children diagnosed with autism spectrum disorder (ASD) to provide valuable insights for the future diagnosis and treatment of ASD. We conducted a retrospective analysis involving 26 children diagnosed with ASD admitted to our hospital between April 2021 and December 2022 (the observation group) and 38 children who underwent health checkups during the same period (the control group). ABR testing was administered to both groups at our hospital. We assessed differences in ABR test results between the observation and control groups and analyzed the correlation between ABR test results and the outcomes of the Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) surveys. Additionally, we examined variations in ABR test results among ASD children across different age groups. In the observation group, we observed higher right ear latencies of waves I and III, as well as differences in left and right ear interpeak latencies (IPLs) of waves I-V compared to the control group (P < .05). However, the left and right ear IPLs of waves III-V were lower in the observation group (P < .05). There were no significant differences in ABR test results among ASD children of different ages (P > .05). Furthermore, we identified positive correlations between the right ear wave III latency, left ear wave I-III IPL, and right ear wave I-III IPL with ABC and CARS scores (P < .05). Children with ASD display abnormal ABR characteristics, indicating the potential of ABR as a valuable tool for evaluating ASD progression in the future.


Genome modifications and cloning using a conjugally transferable recombineering system.
The genetic modification of primary bacterial disease isolates is challenging due to the lack of highly efficient genetic tools. Herein we describe the development of a modified PCR-based, λ Red-mediated recombineering system for efficient deletion of genes in Gram-negative bacteria. A series of conjugally transferrable plasmids were constructed by cloning an oriT sequence and different antibiotic resistance genes into recombinogenic plasmid pKD46. Using this system we deleted ten different genes from the genomes of Edwardsiella ictaluri and Aeromonas hydrophila. A temperature sensitive and conjugally transferable flp recombinase plasmid was developed to generate markerless gene deletion mutants. We also developed an efficient cloning system to capture larger bacterial genetic elements and clone them into a conjugally transferrable plasmid for facile transferring to Gram-negative bacteria. This system should be applicable in diverse Gram-negative bacteria to modify and complement genomic elements in bacteria that cannot be manipulated using available genetic tools.