Demographic and Clinical Profile of Patients With Dementia Receiving Electroconvulsive Therapy: A Case-Control Study.
Little is known about the clinical characteristics of patients with dementia receiving electroconvulsive therapy (ECT) for the treatment of behavioral symptoms. This study examined the demographic and clinical profile of patients with dementia receiving ECT in China. This was a retrospective, case-control study. The sample was composed of 23 patients with dementia treated with ECT and 71 sex- and age-matched controls treated for a period of 8 years (2007-2014) at the National Clinical Research Centre of Mental Disorders, China. Sociodemographic and clinical data were collected from the electronic chart management system. Multiple logistic regression analysis revealed that ECT was independently associated with high risk for suicide at admission. The recorded indications for ECT included both high risk for suicide and aggressive behavior. Most patients responded to ECT satisfactorily (56.5%) or partially (34.8%) with only mild-moderate transient memory impairment (30.4%). Although this is a preliminary study limited by the retrospective design and small sample size, findings suggest that ECT is an effective and safe therapeutic intervention to reduce the risk for suicide and aggressive behavior in dementia.


Arrhythmic Burden and Ambulatory Monitoring of Pediatric Patients with Cardiomyopathy.
Pediatric patients with cardiomyopathy (CM) are at risk for sudden cardiac death (SCD), likely driven by arrhythmic etiologies. Describe arrhythmia burden and Holter utility in pediatric CM including: hypertrophic CM (HCM), dilated CM (DCM), and restrictive CM (RCM). Retrospective cohort study of patients <21 years with CM. Patient demographics, arrhythmic history, and genetic status were reviewed including outcomes of death, aborted SCD, and device shocks. Holter findings were analyzed over the prior 5 years including clinically significant findings and resulting changes to management. Analysis for the composite outcomes of death, aborted SCD, and appropriate shock were performed using logistic regression with backward elimination. One hundred and forty-six patients were included: 83 HCM, 54 DCM, and nine RCM (mean 13 ± 6 years). A total of 23% of patients had defibrillators. There were six deaths (two SCD), four patients with appropriate device therapies, and four aborted SCD episodes. In total, 305 Holter monitors were reviewed. Six Holters had significant findings, all nonsustained ventricular tachycardia. Two Holters resulted in changes in management, both defibrillator implantations. Twelve patients had one or more of the conditions defining the composite outcome. Using logistic regression, clinical history of ventricular arrhythmia, frequent premature ventricular complexes, and CM type were included as potential independent predictors in the final model and clinical ventricular arrhythmia and RCM disease were associated with the composite outcome. SCD and device therapies were relatively rare. Routine Holter screening rarely demonstrated significant findings or changed clinical care. Clinical history of ventricular arrhythmia was associated with poor clinical outcome.


Molecular cloning and characterization of a cDNA clone for a protein specifically expressed in embryo as well as in a chemically induced pancreatic B cell tumor of rat.
cDNAs were molecularly cloned for proteins specifically expressed in embryo as well as in a chemically induced rat pancreatic B cell tumor in which virally related oncogenes such as v-myc, v-src, v-yes, v-mos and v-kis were previously demonstrated not to be expressed. A plasmid cDNA library consisting of 48,000 independent colonies was constructed from poly(A) containing cytoplasmic RNA isolated from 12 day rat embryo. The library was screened by hybridization with 32p-labelled cDNA synthesized from poly(A) containing RNA of rat pancreatic B cell tumor or normal islet B cells. Two clones were obtained which showed a clearly positive reaction only with tumor probe. Nucleotide sequence of one of them harboring insert of 615 nucleotides was determined and its amino acid sequence of 119 residues was deduced, which showed that the protein encoded by this mRNA is highly basic, basic residues/acidic residues being 1.63.


One, two or three? Probing the stoichiometry of membrane proteins by single-molecule localization microscopy.
Probing the oligomeric state of abundant molecules, such as membrane proteins in intact cells, is essential, but has not been straightforward. We address this challenge with a simple counting strategy that is capable of reporting the oligomeric state of dense, membrane-bound protein complexes. It is based on single-molecule localization microscopy to super-resolve protein structures in intact cells and basic quantitative evaluation. We validate our method with membrane-bound monomeric CD86 and dimeric cytotoxic T-lymphocyte-associated protein as model proteins and confirm their oligomeric states. We further detect oligomerization of CD80 and vesicular stomatitis virus glycoprotein and propose coexistence of monomers and dimers for CD80 and trimeric assembly of the viral protein at the cell membrane. This approach should prove valuable for researchers striving for reliable molecular counting in cells.


Multiple types of distress are prospectively associated with increased risk of ovarian cancer.
Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co-occurring distress-related factors are associated with ovarian cancer risk. Five distress-related factors were measured repeatedly over 21 years of follow-up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time-updated count of distress-related factors, in age-adjusted models, then further adjusted for ovarian cancer risk factors and behavior-related health risk factors. Across 1,193,927 person-years of follow-up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress-related psychosocial factors demonstrated increased ovarian cancer risk (HRage-adjusted = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress-related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress-related psychosocial factors was associated with twofold greater ovarian cancer risk (HRage-adjusted = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co-occurring with any other distress-related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates. Presence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened.


Mortality rate of adrenocortical tumors in children under 15 years of age in Curitiba, Brazil.
Several reports refer to an increased frequency of adrenal cortex tumors (ACT) among children in Southern Brazil, yet all data have been derived from hospital-based registries. An inherited germline mutation in the p53 gene (TP53 R337H) is detected in virtually all children with ACT in this region and accounts for the excess cases observed. We reviewed all death certificates that mentioned ACT or adrenal neuroblastoma (NB) and which were reported to the Paraná State Department of Health between 1998 and 2003, for individuals younger than 15 years who resided in the Curitiba metropolitan region. Eight deaths from ACT and ten from NB were identified. The age-standardized mortality rate per million children <15 years of age in the Curitiba metropolitan region during the years 1998-2003 was 1.6 (95% confidence interval (CI) 1.4, 1.8) for ACT and 2.3 (95% CI 2.0, 2.5) for NB. The ratio of the adrenal NB and ACT age-adjusted mortality rates was 1.43. The incidence of ACT estimated from the mortality data, assuming an ACT survival rate of 0.542, was 3.5 (95% CI 2.9, 4.2). Our investigation of population-based mortality confirms the evidence from hospital-based registries of a clustering of ACT in Southern Brazil. In addition, our data suggest that the incidence of ACT in this region is about 12-18 times the incidence reported in the United States and Europe.


Interactions of adriamycin with a calcium binding site.
Terbium (Tb3+) luminescence has been used to investigate the interactions of adriamycin with a specific calcium binding protein, in the plasma membrane of GH3/B6 pituitary tumor cells. The luminescence intensity and lifetime of the Tb3+-GH3/B6 complex was quenched in the presence of adriamycin. According to Stern-Volmer analysis, the quenching of Tb3+-GH3/B6 luminescence was by both membrane bound adriamycin (Ka = 3.7 x 10(5) M-1) and free adriamycin (kq = 7.3 x 10(7) M-1 s-1). The data suggests that, the calcium binding site at the outer surface of the membrane is collisionally accessible to freely diffusing adriamycin; and, that the toxin receptor site is located near the bound metal ion.


Monitoring of reaction kinetics and determination of trace water in hydrophobic organic solvents by a smartphone-based ratiometric fluorescence device.
A smartphone-based ratiometric fluorescence device was designed to monitor the reaction kinetic process under vigorous mixing conditions, demonstrated by the hydrolysis of Cs4PbBr6 nanocrystals (NCs). In the presence of trace water, part of Cs4PbBr6 NCs (non-fluorescent) was converted to CsPbBr3 NCs (strong fluorescent). Using anthracene as the reference fluorophore, the brightness ratio of the green (from CsPbBr3 NCs) to blue (from anthracene) components in the fluorescence image which was recorded in situ by the smartphone camera was measured as the signal for kinetic analysis. It was shown that the water-triggered conversion reaction from Cs4PbBr6 NCs to CsPbBr3 NCs follows the pseudo-second-order kinetic model in the early rapid hydrolysis stage (up to 4 min). With increasing water content, the hydrolysis of Cs4PbBr6 NCs is promoted to yield more CsPbBr3 NCs, which was used to determine trace water in n-hexane, dichloromethane, and toluene with detection limits of 0.031, 0.043, and 0.057 μL mL-1, respectively. The device offers the advantages of portability and low cost for rapid field determination of trace water in hydrophobic organic solvents. Graphical abstract.


The evolving role of abscisic acid in cell function and plant development over geological time.
Abscisic acid (ABA) is found in a wide diversity of organisms, yet we know most about the hormonal action of this compound in the ecologically dominant and economically important angiosperms. In angiosperms, ABA regulates a suite of critical responses from desiccation tolerance through to seed dormancy and stomatal closure. Work exploring the function of key genes in the ABA signalling pathway of angiosperms has revealed that this signal transduction pathway is ancient, yet considerable change in the physiological roles of this hormone have occurred over geological time. With recent advances in our capacity to characterise gene function in non-angiosperms we are on the cusp of revealing the origins of this critical hormonal signalling pathway in plants, and understanding how a simple hormone may have shaped land plant diversity, ecology and adaptation over the past 500 million years.


Hydrophobic interaction chromatography of the rabbit uterine progesterone receptor.
The chromatographic behavior of the rabbit uterine progesterone receptor interaction on several different hydrophobic matrices was characterized. Receptor, prepared in 0.6 M NaCl, exhibited a progressive retardation of elution, followed by retention, on a series of alkyl agarose columns as the length of the alkyl chain [(CH2)nH-] increased (n = 0-10), reflecting the presence of hydrophobic regions on the protein. Adsorption did not occur directly at the steroid binding site of the molecule and did not require activation to the DNA-binding form. Elution could be achieved by a decrease in the ionic strength of the buffer or the addition of glycerol, resulting in partial purification of receptor. Receptor bound tightly to phenyl agarose, although elution of the receptor under mild conditions (decreasing salt gradient, increasing glycerol gradient) resulted in poor yield and only modest purification. Passage of the non-activated progesterone receptor over Reactive Blue Sepharose effectively removed albumin, presumably by a hydrophobic interaction, although receptor was not retained. In the activated form, approximately 25% of receptor was bound to Reactive Blue Sepharose, reflecting an interaction of the Cibacron Blue dye with the polynucleotide binding site of the receptor. Hydrophobic chromatography may be an important adjunct to methods for purification of the progesterone receptor.


N-Heterocyclic Carbene Self-assembled Monolayers on Copper and Gold: Dramatic Effect of Wingtip Groups on Binding, Orientation and Assembly.
Self-assembled monolayers of N-heterocyclic carbenes (NHCs) on copper are reported. The monolayer structure is highly dependent on the N,N-substituents on the NHC. On both Cu(111) and Au(111), bulky isopropyl substituents force the NHC to bind perpendicular to the metal surface while methyl- or ethyl-substituted NHCs lie flat. Temperature-programmed desorption studies show that the NHC binds to Cu(111) with a desorption energy of Edes =152±10 kJ mol-1 . NHCs that bind upright desorb cleanly, while flat-lying NHCs decompose leaving adsorbed organic residues. Scanning tunneling microscopy of methylated NHCs reveals arrays of covalently linked dimers which transform into adsorbed (NHC)2 Cu species by extraction of a copper atom from the surface after annealing.


Prediction of massive blood transfusion in battlefield trauma: Development and validation of the Military Acute Severe Haemorrhage (MASH) score.
The predominant cause of preventable trauma death is bleeding, and many of these patients need resuscitation with massive blood transfusion. In resource-constrained environments, early recognition of such patients can improve planning and reduce wastage of blood products. No existing decision rule is sufficiently reliable to predict those patients requiring massive blood transfusion. This study aims to produce a decision rule for use on arrival at hospital for patients sustaining battlefield trauma. A retrospective database analysis was undertaken using the UK Joint Theatre Trauma Registry to provide a derivation and validation dataset. Regression analysis of potential predictive factors was performed. Predictive factors were analysed through multi-logistic regression analysis to build predictive models; sensitivity and specificity of these models was assessed, and the best fit models were analysed in the validation dataset. A decision rule was produced using a combination of injury pattern, clinical observations and pre-hospital data. The proposed rule, using a score of 3 or greater, demonstrated a sensitivity of 82.7% and a specificity of 88.8% for prediction of massive blood transfusion, with an AUROC of 0.93 (95% CI 0.91-0.95). We have produced a decision tool with improved accuracy compared to any previously described tools that can be used to predict blood transfusion requirements in the military deployed hospital environment.


Adrenoleukodystrophy: impaired oxidation of fatty acids due to peroxisomal lignoceroyl-CoA ligase deficiency.
Very long chain fatty acids (lignoceric acid) are oxidized in peroxisomes and pathognomonic amounts of these fatty acids accumulate in X-adrenoleukodystrophy (X-ALD) due to a defect in their oxidation. However, in cellular homogenates from X-ALD cells, lignoceric acid is oxidized at a rate of 38% of control cells. Therefore, to identify the source of this residual activity we raised antibody to palmitoyl-CoA ligase and examined its effect on the activation and oxidation of palmitic and lignoceric acids in isolated peroxisomes from control and X-ALD fibroblasts. The normalization of peroxisomal lignoceric acid oxidation in the presence of exogenously added acyl-CoA ligases and along with the complete inhibition of activation and oxidation of palmitic and lignoceric acids in peroxisomes from X-ALD by antibody to palmitoyl-CoA ligase provides direct evidence that lignoceroyl-CoA ligase is deficient in X-ALD and demonstrates that the residual activity for the oxidation of lignoceric acid was derived from the activation of lignoceric acid by peroxisomal palmitoyl-CoA ligase. This antibody inhibited the activation and oxidation of palmitic acid but had little effect on these activities for lignoceric acid in peroxisomes from control cells. Furthermore, these data provide evidence that peroxisomal palmitoyl-CoA and lignoceroyl-CoA ligases are two different enzymes.


Hemodynamic evaluation of the Carpentier-Edwards bioprosthesis in the aortic position.
The Carpentier-Edwards bioprosthesis is a glutaraldehyde-fixed porcine xenograft with a fully flexible thin-walled stent. Cardiac catheterization studies were performed in 17 patients to evaluate use of this valve in the aortic position. Hemodynamic studies established a mean peak gradient across the prosthesis of 19 mm Hg (range 5 to 65). The mean effective orifice area was calculated to be 1.6 cm2 (range 0.8 to 3.3). All patients demonstrated an improvement in functional class after operation. Mean left ventricular ejection fraction increased from 51 +/- 16 to 68 +/- 9 percent (P less than 0.004) in eight patients operated on for aortic stenosis, but was not significantly changed in patients operated on for aortic insufficiency. Hemodynamic comparison of the Carpentier-Edwards bioprosthesis with the standard Hancock xenograft showed similar effective orifice areas for the 23 and 25 mm diameter valves. In two patients studied the 21 mm Carpentier valve demonstrated a greater effective orifice area than that previously reported for the standard Hancock xenograft. The Carpentier-Edwards bioprosthesis affords both clinical and hemodynamic improvement when used in the aortic position and may allow improved effective orifice area when used in the smaller aortic root.


Myocardial protection during coronary surgery. Getting the maximum advantage of both cardioplegia and hypothermia.
The author presents a specially timed protocol of a combination of cold cardioplegic arrest and deep total body hypothermia designed to include the best features and to eliminate some of the principal short-comings of these 2 commonly used methods of myocardial preservation. According to this protocol, the operations were divided into 3 periods: (1) About half the number of the peripheral anastomoses are done in the first period while the body is cooled to 20 degrees C and the during which the heart is in cold ischemic cardioplegic arrest. (2) Most or all proximal anastomoses are done in the second period during which body temperature is kept at 20 degrees C and the heart is in a per vias naturales perfused cold arrest. (3) During the third period, the remaining anastomoses are completed while the heart is again in cold ischemic cardioplegic arrest and the body is rewarmed. This method was used in excess of 100 myocardial revascularization procedures with satisfactory clinical results.


Diphenyl diselenide diet intake improves spatial learning and memory deficits in hypothyroid female rats.
Cognitive deficits have been observed in different animal models of adult-onset hypothyroidism. Thus, this study was delineated to evaluate whether diphenyl diselenide, an organoselenium compound with neuroprotective and antioxidant properties, could afford protection against the detrimental effects of hypothyroidism on behavioral parameters. Hypothyroidism condition was induced in female rats by continuous exposure to methimazole (MTZ) at 20 mg/100 ml in the drinking water, during 3 months. MTZ-induced hypothyroid rats were fed with either standard or a diet containing 5 ppm of diphenyl diselenide for 3 months. Behavioral assessments were performed monthly, in the following order: elevated plus maze, open field and Morris water maze. The levels of thyroid hormones in the animals exposed to MTZ were lower than control until the end of experimental period. The rats exposed to MTZ had a significant weight loss from the first month, which was not modified by diphenyl diselenide supplementation. In elevated plus maze test, MTZ exposure caused a reduction on the number of entries of animals in closed arms, which was avoided by diphenyl diselenide supplementation. In Morris water maze, the parameters latency to reach the platform and distance performed to find the escape platform in the test session were significantly greater in MTZ group when compared to control. These cognitive deficits observed in MTZ-induced hypothyroid rats were restored by dietary diphenyl diselenide. The group fed with diphenyl diselenide alone exhibited a better spatial learning and memory capability in some parameters of Morris water maze when compared to the control group. In summary, our data provide evidence of the effectiveness of dietary diphenyl diselenide in improving the performance of control and hypothyroid rats in the water maze test.


Congenital tracheal stenosis: role of CT and high kV films.
Congenital tracheal stenosis is an intrinsic narrowing of the tracheal lumen due to complete cartilaginous rings. We evaluated the role of the chest radiograph, high kV films, CT and bronchoscopy in five patients with congenital tracheal stenosis. CT was superior to chest radiography and high kV films in the evaluation of the presence and extent of the stenosis. CT was superior to bronchoscopy in the evaluation of the distal extent of the stenosis in two patients. In addition, CT is useful in ruling out external compression of the trachea by a mass or associated vascular anomaly.


'Maintaining Talk' among taxi drivers: accomplishing health-protective behaviour in precarious workplaces.
This paper contributes to the body of research on the relationship between language, health (behaviour), and place. Drawing on data from a qualitative study of taxi drivers in Ontario, Canada, it illustrates how talk, a dimension of language, might (re)make and maintain an unconventional, precarious workplace through ameliorating its inherent risks and hazards. It shows how a group of taxi drivers, who work in a large, metropolitan city, and whose workplace comprises physical places such as streets, highways, and taxicabs, and social places characterised by disadvantaged social and economic location, enact different kinds of talk in an effort to protect their health. This finding suggest the need for a broader conceptualisation of health behaviour, and for further research into other occupational groups and/or unconventional workplaces in order to further develop or theorise the concept of talk.


Inhibitory effects of p-dodecylaminophenol on the invasiveness of human fibrosarcoma cell line HT1080.
Cancer is a major cause of death, and the development of new anticancer drugs is urgently needed. Invasion and metastasis are the primary causes of death due to cancer rather than growth of the primary tumor. In the current study, we examined the anti-invasive effects of p-dodecylaminophenol (1), which was developed based on N-(4-hydroxyphenyl)retinamide (2), a synthetic amide of all-trans-retinoic acid (3). In HT1080 cells 1 inhibited growth, induced apoptosis and arrested the cell cycle in S phase in a dose-dependent manner. In addition, 1 significantly suppressed cell invasion, and the activity and mRNA expression of matrix metalloproteinase-9 (MMP-9). Furthermore, the expression of the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which is a negative regulator of MMP-9, was increased by treatment with 1. These results suggest that 1 could be an effective anti-cancer agent that suppresses cell growth through apoptosis induction and cell cycle arrest, which also inhibits cell invasion by decreasing MMP-9 expression due to an increase in RECK. Compound 1 might be useful clinically as a new and potent anticancer agent that could overcome adverse side effects of the retinoids.


Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats.
Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylphenol, has estrogen-like effects. Here, Sprague-Dawley rats were continuously exposed to phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1) or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and continuing throughout. To eliminate estrous cycle influences on DA levels, females were ovariectomized at adulthood. As adults, striatal levels of DA and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were measured in unanesthetized male and female rats via cerebral microdialysis before and for 200 min after an intraperitoneal injection of 2 mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels indicated an isolated effect in genistein-treated females, there were no meaningful differences among treatment groups in baseline levels of DA, DOPAC, or HVA. However, dietary exposure to 500 ppm genistein significantly potentiated amphetamine-stimulated DA release in males and a similar trend was apparent, but not statistically significant, in females. Dietary exposure to 200 or 750 ppm nonylphenol had no significant effects in males or females. These results suggest that dietary genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated DA release.


Effect of peroxynitrite on mechanical properties of human erythrocyte membranes.
Atomic force microscopy showed that treatment of human whole blood with peroxynitrite modified local mechanical and physical characteristics of erythrocyte membranes, specifically, increased their rigidity.


M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication.
Functional polarization of human monocyte-derived macrophages (MDMs) into M1 cells leads to inhibition of R5 HIV-1 replication and viral DNA synthesis in comparison to control, unpolarized cells together with CD4 downregulation from the cell surface and upregulation of CCR5-binding chemokine secretion. We here investigated whether a postentry restriction of virus replication is also induced by M1 polarization of MDM. MDM were first polarized to M1 cells by 18 h stimulation with interferon-[gamma] and tumor necrosis factor-[alpha]; the cytokines were then removed and the cells were infected with vesicular stomatitis virus G-protein pseudotyped enhanced green fluorescence protein HIV-1 (HIV-GFP) generating a single-round infection cycle. HIV-1 expression was monitored in terms of eGFP expression by fluorescence activated cell sorter (FACS) analysis and real-time PCR analysis of total HIV-1 gag DNA, 2-long terminal repeat DNA, proviral DNA, and multiply spliced RNA transcripts. Expression of apolipopoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G), and APOBEC3A was tested by western blotting and FACS analysis. Inhibition of HIV-GFP expression was observed in M1-MDM along with impaired viral DNA synthesis, delayed proviral integration, and reduced proviral transcription. Although APOBEC3G levels were similar in M1 and unpolarized MDM, APOBEC 3A was selectively expressed only by M1 cells. M1 polarization of in-vitro differentiated primary MDM determines a transient, but profound restriction of HIV-1 replication affecting multiple (entry and postentry) steps in the virus life cycle likely involving the upregulated expression of APOBEC3A.


Characterization of semen quality, testicular marker enzyme activities and gene expression changes in the blood testis barrier of Kunming mice following acute exposure to zearalenone.
A total of 95 8-week-old male Kunming mice were randomly assigned into five groups and exposed to zearalenone (ZEA) at doses of 25, 50, and 75 mg/kg delivered by intra-peritoneal (i.p.) injection for 5 days. The testis and epididymis indices involving sperm quality and morphology, testis enzyme activities, serum concentrations of testosterone and estrogen, and the expression levels of the three gene and protein of N-cadherin, vimentin, and claudin 11 related to the blood testis barrier (BTB) were analyzed. Results showed that ZEA significantly decreased body weight and semen quality compared to the control group along with increased activity of alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH), and reduced serum concentrations of testosterone and estrogen. At the mRNA and protein levels, expression of N-cadherin, vimentin, and claudin 11 significantly increased; however, the mRNA and protein of N-cad expression decreased. These data suggest acute exposure to ZEA reduces sperm quality and significantly decreases the concentration of serum testosterone and estradiol. In addition, the activities of the testis marker enzymes and associated mRNA and protein expressions of the BTB were also significantly affected. Our results demonstrated that ZEA has a significant impact on the reproductive parameters of male mice which showed compensatory response to strengthen the barrier function of the BTB following ZEA exposure.


An immunohistochemical study of the effects of surgical induction of anterior disc displacement in the rabbit craniomandibular joint on type I and type II collagens.
The right craniomandibular joint (CMJ) was exposed surgically and all the discal attachments severed except for the posterior one. The disc was then repositioned anteriorly and sutured to the zygomatic arch. The left joint served as a sham-operated control; 10 other joints were used as non-operated controls. Deeply anaesthetized rabbits were perfused with 2% buffered formalin 2 weeks (10 rabbits) or 6 weeks (10 rabbits) after the induction of the anterior disc displacement (ADD). The articular disc, bilaminar zone, mandibular condyle and articular eminence were excised. The condyles and the articular eminences were demineralized in EDTA. All tissues were then sectioned at 10 microns in a cryostat. Sections were incubated with polyclonal antibodies directed against type I or type II collagens. Following incubation in the appropriate fluorescein isothiocyanate-labelled secondary antibodies, these specimens were studied under the fluorescence microscope. At 2 weeks there was a reduction in type II collagen immunostaining; some areas of the experimental condylar cartilage showed a switch from type II to type I collagen. However, at 6 weeks there was an increase in type II collagen immunostaining and a decrease in type I compared to the 2-week group. It is concluded that surgical induction of ADD in the rabbit CMJ leads to alteration in the condylar cartilage collagen phenotype similar to that reported for osteoarthritic cartilage of other synovial joints.


Hypertension is the metabolic syndrome component most strongly associated with microvascular complications and coronary artery calcification in Type 1 diabetes.
To evaluate the association of metabolic syndrome (MetS) and its individual components with microvascular complications and coronary artery calcification (CAC) in patients with Type 1 diabetes. Cross-sectional study included 261 patients with Type 1 diabetes. Patients were assessed regarding the presence of MetS according to National Cholesterol Education Program (NCEP) criteria. CAC score was measured in a subset of 100 patients without known cardiovascular disease. The prevalence of MetS was 13.4% according to the NCEP criteria. Microvascular complications and CAC were more frequent in patients with MetS. In a multiple logistic regression analysis, MetS remained associated with nephropathy [OR: 6.33 (95% CI 2.54-15.77), p<0.001], but not with retinopathy and CAC. Among the MetS components, hypertension was associated with presence of retinopathy [OR: 4.04 (95% CI 1.65- 9.90), p=0.002], nephropathy [OR: 5.92 (95% CI 2.42-14.4), p<0.001] and CAC [OR: 2.97 (95% CI 1.06-8.30), p=0.03]. Hypertension was the only MetS component associated with retinopathy, nephropathy and the presence of CAC. Hypertension was better associated with CAC than MetS itself.


Insight into the effect of microplastics on the adsorption and degradation behavior of thiamethoxam in agricultural soils.
Thiamethoxam and microplastics are both common pollutants in farmland soil; however, few studies have focused on the interaction between thiamethoxam and microplastics in soil. Here, a batch experiment and soil incubation experiment were performed to explore the mechanism and effects of microplastics on the adsorption and degradation behaviors of thiamethoxam in soil, respectively. First, the batch experimental results indicated that the adsorption process of thiamethoxam on the microplastic/soil mixtures and soil-only systems mainly relies on chemical interactions. All sorption processes had moderate intensities of adsorption, and the sorption process occurred on the heterogeneous surface. In addition, the particle size and dose of microplastics could both affect the adsorption behavior of thiamethoxam onto microplastics/soil systems. The sorption capacity of thiamethoxam in soil decreases as the particle size of microplastics increases, but the sorption capacity increases as the dose of microplastics increases. Second, the results of the soil incubation experiment showed that the half-lives of thiamethoxam ranged from 57.7 d to 86.6 d, from 86.6 d to 173.3 d, and 115 d in the biodegradable microplastic/soil systems, nondegradable microplastic/soil systems, soil-only systems, respectively. These results indicate that biodegradable microplastics promoted the degradation of thiamethoxam, while nondegradable microplastics delayed the degradation process of thiamethoxam in soil. Overall, microplastics could change the degradation behaviors, sorption capacity and adsorption efficiency, and then affect the mobility and persistence of thiamethoxam in the soil environment. These findings contribute to understanding the influence of microplastics on the environmental fate of pesticides in the soil environment.


Antihypertensive treatment and new-onset diabetes mellitus.
The various antihypertensive regimens have varying effects on glucose metabolism and the development of diabetes mellitus. Recent large hypertension trials have shown great differences in the development of new-onset diabetes among antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by thiazide diuretics and b-adrenergic blockers, and unchanged or decreased by angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin-receptor blockers. The differences in new-onset diabetes mellitus have not influenced the outcome of cardiovascular mortality and morbidity in all of the large clinical trials, but drug-induced diabetes among hypertensive patients is known to carry the same cardiovascular risk as that seen in patients with previously known diabetes; however, it might take years for the increased risk to become apparent.


The boundary conditions of priming of visual search: from passive viewing through task-relevant working memory load.
Priming of visual search has a dominating effect upon attentional shifts and is thought to play a decisive role in visual stability. Despite this importance, the nature of the memory underlying priming remains controversial. To understand more fully the necessary conditions for priming, we contrasted passive versus active viewing of visual search arrays. There was no priming from passive viewing of search arrays, while it was strong for active search of the same displays. Displays requiring no search resulted in no priming, again showing that search is needed for priming to occur. Finally, we introduced working memory load during visual search in an effort to disrupt priming. The memorized items had either the same colors as or different colors from the visual search items. Retaining items in working memory inhibited priming of the working memory task-relevant colors, while little interference was observed for unrelated colors. The picture that emerges of priming is that it requires active attentional processing of the search items in addition to the operation of visual working memory, where the task relevance of the working memory load plays a key role.


Effect of alendronate on the progression of periodontitis induced by Porphyromonas gingivalis and Fusobacterium nucleatum: a study in rats.
The study aimed to investigate the effect of alendronate (ALN) on the inhibition of alveolar bone loss in experimental periodontitis in Wistar rats. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis with Fusobacterium nucleatum. The rats (n = 80) were randomized as follows: negative control (n = 10); positive control (n = 10); ALN groups: test 8 (n = 10), test 12 (n = 10), and test 16 (n = 10); and placebo groups: control 8 (n = 10), control 12 (n = 10), and control 16 (n = 10). Two milligrams per kilogram of ALN or placebo was administered twice weekly for 8, 12, and 16 weeks. Bone loss was determined by morphological and histological analyses. One independent, blinded examiner (ICC, 0.91) performed the measurements. The distance from the cement enamel junction to the alveolar bone crest of the second lower molar was measured: distal-vestibular (d), furca (f), mesial-vestibular (h), and area. Histometry was performed on the second contralateral molar. Sections (6 μm) were used to determine the furcation bone area (A-FB). The following statistical analyses were conducted: Mann-Whitney and Kruskal-Wallis. PC group developed periodontitis (p < 0.0001). Morphometric analysis determined that ALN was effective in T8 for linear measurements d, f, and h (p < 0.05). No significant differences occurred at test 8, test 12, and test 16. Analysis of A-FB revealed no significant differences between the ALN and placebo groups at 8 and 16 weeks (p > 0.05). ALN was effective against bone loss in relation to A-FB after 12 weeks (p < 0.0001). According to the methodology used, the results suggest that oral administration of ALN could influence alveolar bone loss in rats submitted to experimental periodontitis. ALN could be a potential therapeutic approach when associated with periodontal treatment.


Asthma control in children is associated with nasal symptoms, obesity, and health insurance: a nationwide survey.
This study aimed to estimate the prevalence of asthma control and determinants of poor control in the Portuguese pediatric population (<18 years); secondarily, we described asthma-related healthcare services and medication use. Data of 98 children with current asthma, from the second phase of a nationwide population-based telephone survey (INAsma study), were analyzed. Asthma control definition was based on GINA criteria, grouping partially controlled and uncontrolled asthma as 'not-controlled asthma' (NCA). We used multivariate logistic regression to study factors associated with NCA and with unscheduled medical visits for asthma. About half of the children had NCA (49%, 95% CI 39-59%). In the multivariate model, risk factors for NCA were as follows: substantial nasal symptoms (a OR 6.80), overweight/obesity (a OR 3.44), and not having health insurance (a OR 3.78). All the children with NCA had nasal symptoms, and the lack of asthma control was also associated with the increasing number of nasal symptoms (p < 0.001). In the previous year, 90% (95% CI 84-96%) of children with current asthma had healthcare visits and 67% (95% CI 58-77%) used medication for asthma. The risk of unscheduled medical visits was higher in children with nasal symptoms (a OR 3.63) and in those without health insurance (a OR 2.79), and lower in adolescents (a OR 0.19). Half of the children with asthma were poorly controlled. Nasal symptoms and obesity are important determinants of asthma control. Children without health insurance are at greater risk of poor asthma outcomes; this association is reported for the first time in a European country.


Prevalence and prognostic role of PD-L1 in patients with gynecological cancers: A systematic review and meta-analysis.
Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC). Several electronic databases were searched. Fixed effects models or random effects models were employed to calculate the pooled prevalence of PD-L1 positivity and pooled hazard ratios (HRs) as appropriate. Heterogeneity and publication bias were also assessed. The pooled prevalence of PD-L1 positivity was 58.1%, 33.8% and 37.5% for CC, EC and OC patients, respectively. There were significant differences in the pooled estimates after stratification by PD-L1-positive assessment criteria and antibody clones. PD-L1 positivity was associated with worse OS in CC and EC patients and poorer progression-free survival (PFS) in CC patients. The prevalence of PD-L1-positive expression was considerably high in CC and modestly high in EC and OC patients. PD-L1 expression has the potential to be a prognostic biomarker for predicting the clinical outcomes of patients with CC and EC but not OC.


Oral magnesium load test for the assessment of intestinal magnesium absorption. Application in control subjects, absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism.
The intestinal absorption of magnesium (Mg) was estimated from the increment in urinary Mg following oral administration of 25 mmol of Mg. Fasting urinary Mg did not differ between the control group and patient groups (absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism). As compared to the value in the control group, the increment in urinary Mg above the fasting value was not significantly different in absorptive hypercalciuria. However, it was significantly increased in primary hyperparathyroidism and significantly reduced in hypoparathyroidism. In control subjects, the increment in urinary Mg was much higher during a low than during a high calcium diet. The results suggest that 1,25-(OH)2-vitamin D stimulates Mg absorption, since Mg absorption was elevated in situations associated with stimulated 1,25-(OH)2-vitamin D synthesis (primary hyperparathyroidism and low calcium diet) and reduced in a condition characterized by low 1,25-(OH)2-vitamin D production (hypoparathyroidism). Moreover, the data indicate that 1,25-(OH)2-vitamin D may not be pathogenetically important in absorptive hypercalciuria, since Mg absorption was normal.


Does green finance mitigate the effects of climate variability: role of renewable energy investment and infrastructure.
Few researches have inspected the task of green finance in reducing CO2 emissions, while earlier studies have inspected the influence of economic development on carbon emissions. A green finance development index is built using four indicators to fill in this knowledge gap: green credit, green insurance, green securities, and green investing. Using data spanning the years 2005-2019, a panel quantile regression is applied to investigate the links between green finance, renewable energy, and CO2 emissions. Increases in renewable energy use and advances in the green finance development index have contributed to a reduction in CO2 emissions from BRICS countries. CO2 emissions on the other hand slowed the growth of renewable energy use, slowed the flow of investment to green projects, and ultimately hampered the development of green finance. There was also a clear policy-driven influence on renewable energy spending in the countries of the BRICS region. Green finance policies, on the other hand, have consistently failed to have a long-term impact. Therefore, rising the consumption of renewable energy and creating a carbon trading market are all part of this study's recommendations for green finance policy improvement.


Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1.
DNA replication ensures the accurate transmission of genetic information during the cell cycle. Histone variant H2A.Z is crucial for early replication origins licensing and activation in which SUV420H1 preferentially recognizes H2A.Z-nucleosome and deposits H4 lysine 20 dimethylation (H4K20me2) on replication origins. Here, we report the cryo-EM structures of SUV420H1 bound to H2A.Z-nucleosome or H2A-nucleosome and demonstrate that SUV420H1 directly interacts with H4 N-terminal tail, the DNA, and the acidic patch in the nucleosome. The H4 (1-24) forms a lasso-shaped structure that stabilizes the SUV420H1-nucleosome complex and precisely projects the H4K20 residue into the SUV420H1 catalytic center. In vitro and in vivo analyses reveal a crucial role of the SUV420H1 KR loop (residues 214-223), which lies close to the H2A.Z-specific residues D97/S98, in H2A.Z-nucleosome preferential recognition. Together, our findings elucidate how SUV420H1 recognizes nucleosomes to ensure site-specific H4K20me2 modification and provide insights into how SUV420H1 preferentially recognizes H2A.Z nucleosome.


Effects of high salt intake on control of hindlimb vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats.
1. This study aimed to examine whether a high salt diet alters control of vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). 2. SHR and WKY aged 8 weeks were fed either high (8%) or normal salt (0.4%) diet for 4 weeks. Arterial baroreflex control of hindlimb vascular resistance was assessed by examining reflex-induced vasodilation and vasoconstriction in response to phenylephrine and nitroprusside, respectively, in the constant-flow perfused hindlimb of urethane-anesthetized rats. 3. Tonic influence of the cardiopulmonary vagal afferents was evaluated by examining the effects of vagotomy on hindlimb vascular resistance and on the gain of arterial baroreflex control of hindlimb vascular resistance. 4. The gain of the arterial baroreflex control of hindlimb vascular resistance in response to both phenylephrine and nitroprusside were not significantly different between SHR receiving high and normal salt diets, and between WKY receiving high and normal salt diets. 5. Vagotomy increased hindlimb vascular resistance in all four groups of rats. However the high salt diet than those in SHR on a normal salt diet but similar between the two groups of WKY. Vagotomy increased the slope of arterial baroreflex control of hindlimb vascular resistance in SHR receiving a normal salt diet and the two groups of WKY but not in SHR receiving a high salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)


A decreased ratio of height of lateral femoral condyle to anteroposterior diameter is a risk factor for anterior cruciate ligament rupture.
Studies have shown that the spherical shape of the lateral femoral condyle has a clear relationship with the relative axial movement of tibiofemoral joint and the anterior cruciate ligament (ACL) rupture. The purpose of this study was to describe the distal curvature of the lateral femoral condyle by ratio of height of lateral femoral condyle to anteroposterior diameter (HAPR), and evaluate its correlation with ACL rupture. A retrospective case-control study of 64 patients was conducted. Two age-and sex-matched cohorts (each n = 32) were analyzed: primary ACL ruptures, and a control group consisting of isolated meniscal tears. On the radiograph, the distance from the intersection of the axis of the distal femur and the anteriorly diameter of the lateral femoral condyle to the lower point of the lateral femoral condyle divided by the anteriorly diameter of the lateral femoral condyle is HAPR. The HAPR was measured by digital radiograph imaging systems (DR) to quantify femoral sphericity. Cutoff values were defined; and diagnostic performance of the risk factors was assessed. Meanwhile, we measured the posterior tibial slope (PTS) on radiograph and compared the two methods to evaluate the significance of HAPR in predicting ACL rupture. A total of sixty-four patients who met the inclusion criteria were included in the final analysis (32 with primary ACL rupture, 32 controls). The HAPR was smaller in the knees with primary ACL rupture (0.31 ± 0.02) than that of the control group (0.33 ± 0.02) (p < 0.01). The PTS was bigger in the knees with primary ACL rupture (8.18 ± 2.77) than that of the control group (6.61 ± 2.85) (p = 0.036). The AUC of HAPR was bigger (0.825; 95% CI, 0.72-0.93) than that of PTS (0.675; 95%CI, 0.85-0.81). The calculated cutoff of HAPR of 0.32 (Youden index, 0.56) was associated with an increased risk for ACL rupture, with sensitivity of 75% and specificity of 81% to predict an ACL rupture. This study showed that a decreased HAPR is associated with an ACL rupture, and the decrease of HAPR was more significant in predicting ACL ruptures than the PTS. This helps clinicians identify susceptible individuals who may benefit from targeted ACL rupture prevention counseling and intervention.


Fungal biotechnology.
Fungi are used in many industrial processes, such as the production of enzymes, vitamins, polysaccharides, polyhydric alcohols, pigments, lipids, and glycolipids. Some of these products are produced commercially while others are potentially valuable in biotechnology. Fungal secondary metabolites are extremely important to our health and nutrition and have tremendous economic impact. In addition to the multiple reaction sequences of fermentations, fungi are extremely useful in carrying out biotransformation processes. These are becoming essential to the fine-chemical industry in the production of single-isomer intermediates. Recombinant DNA technology, which includes yeasts and other fungi as hosts, has markedly increased markets for microbial enzymes. Molecular manipulations have been added to mutational techniques as a means of increasing titers and yields of microbial processes and in the discovery of new drugs. Today, fungal biology is a major participant in global industry. Moreover, the best is yet to come as genomes of additional species are sequenced at some level (cDNA, complete genomes, expressed sequence tags) and gene and protein arrays become available.


The chemical structure and genetic locus of Campylobacter jejuni CG8486 (serotype HS:4) capsular polysaccharide: the identification of 6-deoxy-D-ido-heptopyranose.
In line with our on-going efforts to create a multivalent anti-Campylobacter jejuni vaccine based on its capsule polysaccharides (CPSs), we report here the chemical structure and the genetic locus of the CPS produced by C. jejuni strain CG8486, which belongs to the serotype HS:4 CPS complex. C. jejuni CG8486 CPS was observed to be composed of approximately 17 disaccharide repeating blocks of 4-substituted N-acetyl-beta-D-glucopyranosamine and 3-substituted 6-deoxy-beta-D-ido-heptopyranose. A small number of 6-deoxy-beta-D-ido-heptopyranose units were observed to carry O-methyl phosphoramidate moieties at the O-2 or O-7 position. The gene content and organization of the CPS locus of C. jejuni CG8486 were comparable to those of C. jejuni strains NCTC 11168 and 81-176, but several CG8486 CPS genes were observed to be more divergent from those present in the CPS loci of NCTC 11168 and 81-176 CPS, which indicated that there are genetic characteristics specific to the C. jejuni HS:4 CPS complex. The efficacy of a glycoconjugate vaccine based on C. jejuni CG8486 CPS is presently being tested in an animal model, the results of which will be presented in future communications.


The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia.
This study examined the induction of electroretinogram abnormalities in hyperglycemia and the possible role of increased polyol pathway activity in the development of these changes. Both diabetic hyperglycemia and galactosemia caused the prolongation of peak latencies and in some cases a reduction in the amplitudes of oscillatory potentials on the b-wave. Diabetic hyperglycemia-associated abnormalities were prevented and normalized by insulin or ADN-138, an aldose reductase inhibitor. Galactosemia-induced abnormalities were inhibited by ADN-138, and were reversed either by ADN-138 treatment or by withdrawal of galactose from the diet. Polyol accumulation was prevented by insulin or ADN-138, and the elevated polyol level was reversed by insulin, ADN-138, or withdrawal of galactose in diabetic hyperglycemia and/or galactosemia. These results suggest that the increased polyol pathway activity in the hyperglycemia may be involved in the development of electroretinogram abnormalities similar to those in human diabetes; therefore, ADN-138 could be a useful drug for therapy of retinopathy in the early diabetic stage.


Prognostic significance of arrhythmia inducibility or noninducibility at initial electrophysiologic study in survivors of cardiac arrest.
The value of arrhythmia inducibility or noninducibility at initial electrophysiologic study to predict the likelihood of arrhythmia recurrence was assessed in 150 consecutive survivors of cardiac arrest. Ventricular tachycardia (greater than or equal to 6 beats) or ventricular fibrilation was induced in 113 patients (75%); ventricular arrhythmia could not be induced in 37 patients (25%). During follow-up of a mean of 16 months (range 1 to 72), there were 65 arrhythmia recurrences, 34 of them fatal, in 58 patients. Multivariate regression analysis showed that inducibility at initial study of ventricular tachycardia or ventricular fibrilation was an independent predictor of total arrhythmia recurrence (p less than 0.0001) and fatal arrhythmia recurrence (p = 0.02). At 1 year, 25 +/- 5% of patients with an inducible arrhythmia had a fatal arrhythmia recurrence compared with only 4 +/- 4% of patients without (p = 0.003). The nature of the inducible arrhythmia had no additional predictive value. Inducibility or noninducibility of ventricular arrhythmias at initial electrophysiologic study is a powerful, independent predictor of subsequent arrhythmia recurrence in survivors of cardiac arrest. Patients without inducible arrhythmias have a low frequency of fatal arrhythmia recurrence.


Replicon typing of plasmids encoding resistance to newer beta-lactams.
Polymerase chain reaction-based replicon typing represents a novel method to describe the dissemination and follow the evolution of resistance plasmids. We used this approach to study 26 epidemiologically unrelated Enterobacteriaceae and demonstrate the dominance of incompatibility (Inc) A/C or Inc N-related plasmids carrying some emerging resistance determinants to extended-spectrum cephalosporins and carbapenems.


Characteristics of dysphagia in children with cerebral palsy.
Videofluoroscopic modified barium swallow (VMBS) examinations may provide clinically relevant information regarding deglutition in children with cerebral palsy and dysphagia. A retrospective review of clinical evaluations and VMBS studies on 90 consecutive children with cerebral palsy and dysphagia was completed. Most children were referred because of concerns regarding airway protection during oral feedings. Most children had multiple disabilities and 93% were nonambulatory. The majority of children were totally dependent for oral feedings (80%). Oral and pharyngeal phase abnormalities were present in almost all patients. Abnormalities of deglutition were observed only while swallowing specific food textures in the majority of patients. Aspiration of specific food textures was significantly more common than aspiration of all food textures (p < 0.0001). Finally, aspiration was silent in 97% of the patients. VMBS studies can provide clinicians with valuable information regarding the most appropriate food textures and rates of oral feeding for children with cerebral palsy and dysphagia.


Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients.
Several studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and β cell function. This characterization has a potential importance with regard to T1AD patients' stratification and follow-up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1β, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0·45; P = 0·011) and CCL2 (r = -0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = -0·38; P = 0·027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.


Predictive accuracy of standard computed tomography scanning in the diagnosis of Chiari malformation Type I in children.
In this study, retrospective data analysis was performed to analyze the utility of head computed tomography (CT) scanning in the diagnosis of Chiari malformation Type I (CM-I) in the pediatric population. The authors conducted a retrospective review of radiology charts describing head CT results obtained at Columbus Children's Hospital between January 2004 and January 2005. The records were searched for the key words "Chiari," "cerebellar ectopy," or "tonsillar ectopy." The exclusion criteria included patients with previously known Chiari malformation Type I or Type II or those who had undergone follow-up magnetic resonance (MR) imaging at other institutions. Head CT and MR images for the remaining patients were reviewed to verify accuracy. Of the 72 patients with suspicious findings of tonsillar ectopy on CT, only 37 (51.4%) had MR imaging findings consistent with CM-I. The tonsillar ectopy in these patients ranged from 3 mm to 17 mm below the foramen magnum. The authors' findings indicate that incidental standard CT scans of the head have limited value in identifying CM-I.


Helicobacter pylori and recurrent pain abdomen.
Pain abdomen is a common problem in childhood. Many factors i.e., organic changes in the gut, psychological and environment contribute to recurrent pain abdomen (RAP) in children. Helicobacter pylori infects children very early in childhood and stays indefinitely in the gut without its eradication. It may be responsible for pain abdomen and peptic ulcers in children. This study was done to assess the HP status in children with RAP diagnosed and evaluate the effects of eradication of HP infection in them. 76 children were included in the study. Out of 76 children studied 14.8% had evidence of a secondary cause for pain abdomen and responded to appropriate therapy. 65.45% of children who had undergone UGIE, had evidence of HP infection in the upper gastrointestinal tract. Most of these children responded to HP eradication therapy by becoming free of abdominal pain after the eradication therapy with OCA or OMA regimen. We could not do repeated endoscopies in all of them to prove the eradication due to parents' refusal and this is the main drawback of this study. However, in view of clinical response to HP eradication therapy in almost all the cases, we strongly advocate this therapy for those children with RAP, in whom HP infection of the upper gastrointestinal tract can be established beyond doubt.


[Are we prepared for a disaster? Spanish multicentre study].
Paediatric Emergency Departments (PED) should have written disaster plans, to ensure a rapid and efficient response. 1) to determine if Spanish PED have written disaster plans, 2) to describe the characteristics of these plans, and 3) if paediatric victims were included in them. Descriptive multicentre study based on questionnaires sent to physicians in charge of different Spanish PED. The structured survey included questions about external emergency plans (EEP) and internal emergency plans (IEP). Twenty-five out of 44 surveys were replied. Eighteen PED had an EEP, most of them had been written 10 years ago and were reviewed every 3 years or more. In 11/18 PED, the EEP was well-known by health care providers. Drills were never performed in 13/18 PED. Twenty-one PED had an IEP, most of them had been written 8 years ago and were reviewed every 3 years or more. In 13/21 PED, IEP was well-known by health care providers but drills were never performed in 12/21 PED. IEP included evacuation plans (22), fire emergency plans (19), bomb threat plan (13) and flood plans (9). Nine PED have paediatric-specific disaster plans and in 7 PED, disaster plans included adult and paediatric victims. Children were not included In 1 EEP and in 5 IEP. Most of PED have written disaster plans, but these plans are old, unknown by health care providers and almost half of them do not include paediatric victims. It is necessary to improve disaster planning in Spanish PED.


Serum immunoglobulin G levels are positively related to reproductive performance in a long-lived seabird, the common tern (Sterna hirundo).
The evolution of longevity requires a low risk of mortality from extrinsic factors, relative to intrinsic factors, so that individuals that differentially invest in physiological self-maintenance and minimize their annual reproductive costs will maximize lifetime fitness through a prolonged reproductive lifespan. The trade-off between reproductive effort and self-maintenance, as measured by immune function, has been well documented in short-lived birds, but is difficult to demonstrate in long-lived birds. To assess self-maintenance in a long-lived seabird, we measured serum protein levels, including immunoglobulin G (IgG = IgY), in 30 breeding pairs of common terns (Sterna hirundo) and their first-hatched (A) chicks. Most parents were of known age from banding as hatchlings; our sample was selected to contrast young breeders (6-9 years) with very old birds (17-23 years). Body-mass of the parents declined by 5% during the chick-rearing period, while serum protein levels were stable. Serum IgG levels were higher in parents of offspring with faster growth rates, while IgG levels were lower in parents whose broods were reduced by starvation. A-chicks in broods of two had higher IgG levels than singleton chicks. Albumin levels were not related to reproductive performance. Thus, despite adequate statistical power, we could find no evidence for a trade-off between reproduction and self-maintenance in common terns, even in old age. The results are consistent with life-history predictions for long-lived vertebrates, in which selection favors sustained self-maintenance across the reproductive lifespan. The positive relationships between IgG levels and reproductive performance indicate that IgG can be used as an index of parental "quality."


A second wave of topological phenomena in photonics and acoustics.
Light and sound are the most ubiquitous forms of waves, associated with a variety of phenomena and physical effects such as rainbows and echoes. Light and sound, both categorized as classical waves, have lately been brought into unexpected connections with exotic topological phases of matter. We are currently witnessing the onset of a second wave of active research into this topic. The past decade has been marked by fundamental advances comprising two-dimensional quantum Hall insulators and quantum spin and valley Hall insulators, whose topological properties are characterized using linear band topology. Here, going beyond these conventional topological systems, we focus on the latest frontiers, including non-Hermitian, nonlinear and non-Abelian topology as well as topological defects, for which the characterization of the topological features goes beyond the standard band-topology language. In addition to an overview of the current state of the art, we also survey future research directions for valuable applications.


Redox and heavy metal effects on the biochemical activities of an Arabidopsis polyadenylation factor subunit.
The Arabidopsis CPSF30 ortholog (AtCPSF30) is an RNA-binding endonuclease that is part of the plant polyadenylation complex. Previous work (B. Addepalli, A.G. Hunt, Nucleic Acids Res. 35 (2007) 4453-4463) demonstrated that different zinc finger motifs in the protein were responsible for RNA-binding and nuclease activity, respectively. In this study, a more detailed functional map of AtCPSF30 is presented, a map that includes descriptions of novel biochemical activities. Elevated temperatures, the specific zinc chelator 1,10-phenanthroline, and the sulfhydryl reagent dithiothreitol all had differential inhibitory effects on the RNA-binding and nuclease activities. The endonuclease activity of AtCPSF30 was inhibited by relatively high (>100muM) concentrations of zinc, and this inhibition required a plant-specific N-terminal domain apart from the zinc finger core of the protein. ATP stimulated the nuclease activity in the presence of zinc, and this stimulation required a plant-specific C-terminal domain, again apart from the zinc finger core. These studies reveal a subtle and unexpected complexity to AtCPSF30, and raise the possibility that multiple avenues of regulation may impinge on this protein through different functional domains.


Association Between Disabilities, Educational Attainment, Literacy, and Intimate Partner Violence: Findings from the Indian National Family Health Surveys.
Intimate partner violence (IPV) is widespread across the Global South, including India, due to cultural and patriarchal norms that encourage and facilitate such behaviors. These include age at marriage, community- and individual-level encouragement of IPV, and limited access to education across the Global South, particularly for women. Despite this, little research has sought to disentangle the role that disabilities play in affecting women's risk of IPV in India. The current study analyzes a sample of currently married women (N = 114,901) from the nationally representative 2015-2016 and 2019-2021 National Family Health Surveys (NFHS) to assess whether a relationship exists between these dimensions, while controlling for well-known IPV correlates, with physical IPV and controlling behaviors. Logistic regression analyses revealed that persons with cognitive/intellectual disabilities as well as blind respondents were more likely to experience physical IPV. Blind respondents were also more likely to experience controlling behavior. Further, findings indicate that those with no or some education were more likely to experience physical IPV relative to those with higher education. Findings from the current study demonstrate the need for IPV reduction policies to ensure that adequate accommodations are available to facilitate help-seeking behaviors among persons with disabilities. Tailored prevention policies are also needed which consider both context- and location-specific factors associated with risk.


Process engineering of human pluripotent stem cells for clinical application.
Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells, constitute an extremely attractive tool for cell therapy. However, flexible platforms for the large-scale production and storage of hPSCs in tightly controlled conditions are necessary to deliver high-quality cells in relevant quantities to satisfy clinical demands. Here we discuss the main principles for the bioprocessing of hPSCs, highlighting the impact of environmental factors, novel 3D culturing approaches and integrated bioreactor strategies for controlling hPSC culture outcome. Knowledge on hPSC bioprocessing accumulated during recent years provides important insights for the establishment of more robust production platforms and should potentiate the implementation of novel hPSC-based therapies.


Determination of hemoglobin adducts of arylamines in humans.
Aromatic amines and nitroarenes are important occupational and environmental pollutants. It is therefore essential to have fast and reliable methods to monitor human exposure. In rat experiments it has been shown that several arylamines form hydrolyzable hemoglobin adducts. Hemoglobin adducts are dosimeters for the internal dose and possibly for DNA modification at the site of tumor formation. In the present paper we introduce a new efficient method to quantify hemoglobin adducts. Precipitated hemoglobin was hydrolyzed in base in the presence of the recovery standards d5-aniline, d4-2-methylaniline, d4-3-methylaniline, d4-4-methylaniline, d3-2,4-dimethylaniline, 13C6-4-chloroaniline, d9-4-aminobiphenyl, and 4'-fluoro-4-aminobiphenyl. The hydrolysate was extracted with hexane, derivatized with pentafluoropropionic anhydride (PFPA) and analyzed by GC-MS with negative chemical ionization. In one run over twenty amines can be determined. The method has been applied to human studies.


Role of surgery in limited (T1-2, N0-1) cancers of the oropharynx.
To define the role of surgical staging in limited (T1-2, N0-1) oropharyngeal squamous cell cancers. Retrospective. Forty-nine limited oropharyngeal squamous cell cancers of the tonsil, tongue base, or posterior pharyngeal wall-treated surgically were identified. Thirty-five percent were cT1 and 65% were cT2 tumors although 58% were cN0 and 42% were cN1. Forty-six patients underwent neck dissections. Surgical staging altered T-stage in 26% (13/49), nodal status in 23% (11/46), and clinical staging in 40% (20/49) of patients. Among 35 disease-free patients, 28% (4/20) of stage I/II patients received postoperative radiation and chemotherapy was avoided in 80% (12/15) of stage III patients. T1 tumors seemed to have better outcomes (P = .06). The 3 year disease-free survival and 5 year overall survival was 85% and 83%, respectively. Surgical staging identifies patients in whom intensification of treatment with chemotherapy can be most appropriately applied, and enables de-intensification of therapy in pathology confirmed stage I/II disease.


Psychiatric consultation on an otolaryngology liaison service.
Otolaryngology patients (especially those with tracheostomies) present a significant challenge to psychiatrists from both a diagnostic and therapeutic standpoint. To date, no study has been made of psychiatric disorders among this important group of patients. At the Mount Sinai Medical Center, a liaison psychiatrist has been involved with a specialized otolaryngology cluster unit since 1979. Using a 384-item computerized database protocol developed at Mount Sinai, data on 139 otolaryngology patients were recorded and compared with 1662 "Other" inpatient psychiatric consultations on the medical and surgical services during 1980-1987. The otolaryngology patients as a group were more likely to be male (p = 0.011), married (p = 0.001) and employed (p less than 0.001). Cancer was the most common medical disorder, and the average level of stress as reported on DSM-III's Axis IV (5.1, severe) was significantly greater (p less than 0.0001) than that for the "Other." The most common psychiatric response was adjustment disorder (36%). The length of stay of those ENT patients seen in psychiatric consultation was 26.4 days, in contrast to 11.1 days for all ENT patients. However, the length of stay of those patients on ENT receiving a psychiatric consultation was not different from the "Other" psychiatric consultation cohort (26.3 days). Despite the higher level of stress, the incidence of significant psychiatric morbidity was lower for the ENT cohort. The primary effect of the liaison psychiatrist was to lower the threshold for case identification that enhanced the referral rate on the ENT unit.


[Dorsal plate arthrodesis of the thumb metacarpophalangeal joint].
Elimination of pain or instability by arthrodesis of the thumb joint in functional position by dorsal plateosteosynthesis. Painful primary or secondary arthrosis of the thumb, nonreconstructable ulnar, radial or palmar instability, posttraumatic dislocation, defect injuries, bone tumors in the region of the thumb metacarpophalangeal joint. Local infection of the thumb metacarpophalangeal joint area. Dorsal approach to the thumb metacarpophalangeal (MP) joint, splitting of the extensor aponeurosis between the extensor pollicis longus and extensor pollicis brevis tendon. Opening of the anterior capsule and separation of the collateral ligaments, open up the joint, narrow concave and convex joint surface resections, adjustment of the arthrodesis position in 10-20° flexion and K‑wire transfixation, dorsal plateosteosynthesis, fine adjustment of the flexion, axis and pronation position. Closure of the capsule and the periosteal gliding tissue over the plate, reconstruction of the extensor aponeurosis. Splint for 3 weeks. Full load after 6-8 weeks. The dorsal plate arthrodesis of the thumb MP joint is a reliable surgical method with very good functional results.


A nomogram based on pretreatment clinical parameters for the prediction of inadequate biochemical response in primary biliary cholangitis.
Ursodeoxycholic acid (UDCA) has been widely recommended as the first-line drug for primary biliary cholangitis (PBC) in the current guidelines. However, its therapeutic effects are poor in nearly one-third of patients. The early identification and intervention of these patients is crucial for delaying disease progression. Therefore, we explored risk factors for inadequate biochemical response and constructed a nomogram to predict the potential risk. We enrolled 356 patients and randomly divided them into training (70%) and validation groups (30%). We defined inadequate biochemical response as the study endpoint. Logistic analysis was used to identify the independent predictors of poor biochemical response. Based on these factors, a predictive nomogram was finally constructed. Then, discrimination and calibration were evaluated by internal validation. Additionally, the association between the model predictions and prognosis was further analyzed. Female sex, and albumin and bilirubin concentrations were identified as risk factors, and a nomogram was built based on these factors. The areas under the ROC curves of the training and validation groups were 0.809 and 0.791, respectively. Moreover, calibration curves showed that predictions of the nomogram had good concordance with the actual outcomes. The correlation analysis demonstrated that PBC patients with a high probability of a suboptimal biochemical response were more likely to have adverse outcomes. We constructed a nomogram, which can accurately predict the risk of inadequate biochemical response to UDCA, facilitating the early screening of high-risk patients with PBC who should be prioritized for additional therapy.


Biochemical determinants of apoptosis and necrosis.
Although apoptosis and necrosis were originally thought to be entirely distinct mechanisms of cell death, recent work has shown that the processes are regulated by many of the same biochemical intermediates, most notably the levels of cellular ATP, Ca2+, reactive oxygen species, and thiol antioxidants. Beyond a certain threshold, it appears that stress-induced changes in these modulators 'switches' the cell death mechanism from apoptosis to necrosis. Importantly, even when this occurs, cell death can be attenuated by bcl-2 and caspase inhibitors, which are known for their abilities to block apoptosis. This review will summarize these observations within the context of what is currently known about the effector machinery for apoptotic cell death, and possible mechanistic explanations for the switch between apoptosis and necrosis will be provided.


Abscisic acid analogs as chemical probes for dissection of abscisic acid responses in Arabidopsis thaliana.
Abscisic acid (ABA) is a phytohormone known to mediate numerous plant developmental processes and responses to environmental stress. In Arabidopsis thaliana, ABA acts, through a genetically redundant family of ABA receptors entitled Regulatory Component of ABA Receptor (RCAR)/Pyrabactin Resistant 1 (PYR1)/Pyrabactin Resistant-Like (PYL) receptors comprised of thirteen homologues acting in concert with a seven-member set of phosphatases. The individual contributions of A. thaliana RCARs and their binding partners with respect to specific physiological functions are as yet poorly understood. Towards developing efficacious plant growth regulators selective for specific ABA functions and tools for elucidating ABA perception, a panel of ABA analogs altered specifically on positions around the ABA ring was assembled. These analogs have been used to probe thirteen RCARs and four type 2C protein phosphatases (PP2Cs) and were also screened against representative physiological assays in the model plant Arabidopsis. The 1'-O methyl ether of (S)-ABA was identified as selective in that, at physiologically relevant levels, it regulates stomatal aperture and improves drought tolerance, but does not inhibit germination or root growth. Analogs with the 7'- and 8'-methyl groups of the ABA ring replaced with bulkier groups generally retained the activity and stereoselectivity of (S)- and (R)-ABA, while alteration of the 9'-methyl group afforded an analog that substituted for ABA in inhibiting germination but neither root growth nor stomatal closure. Further in vitro testing indicated differences in binding of analogs to individual RCARs, as well as differences in the enzyme activity resulting from specific PP2Cs bound to RCAR-analog complexes. Ultimately, these findings highlight the potential of a broader chemical genetics approach for dissection of the complex network mediating ABA-perception, signaling and functionality within a given species and modifications in the future design of ABA agonists.


Rapid reversal of denervation supersensitivity of dopamine D1 receptors by l-dopa or a novel dopamine D1 receptor agonist, A68930.
The present report describes the effects of sub-chronic treatment with l-dopa or with a recently characterized, selective dopamine D1 receptor agonist (A68930) on the denervation-induced behavioral supersensitivity of the dopamine D1 receptor. Rats with unilateral 6-OHDA lesions of the nigrostriatal pathway, when treated for four successive days with l-dopa + carbidopa show robust contralateral rotation on each day. However, after three days of l-dopa + carbidopa treatment lesioned animals show a significant loss of behavioral supersensitivity to the dopamine D1-selective agonists, A68930 and SKF38393. When lesioned animals were treated daily with A68930, by the second day they showed a virtually complete loss of responsiveness to a dose of the dopamine D1 agonist which previously produced near maximal rotation. In contrast, locomotor hyperactivity to A68930 by intact rats was undiminished over five successive treatment days. These data demonstrate rapid and substantial diminution of the supersensitivity of the denervated dopamine D1 receptor following treatment with l-dopa + carbidopa or with a selective dopamine D1 agonist, while normosensitive dopamine D1 receptor-mediated locomotion in non-lesioned rats is unaltered.


Complete Genome Sequence of Soil Fungus Aspergillus terreus (KM017963), a Potent Lovastatin Producer.
We report the complete genome of Aspergillus terreus (KM017963), a tropical soil isolate. The genome sequence is 29 Mb, with a G+C content of 51.12%. The genome sequence of A. terreus shows the presence of the complete gene cluster responsible for lovastatin (an anti-cholesterol drug) production in a single scaffold (1.16).


Molecular Characterization of Trypanosoma cruzi Reactivation and Follow-up in a Case Series of People With HIV.
We characterize Trypanosoma cruzi infections from blood and cerebrospinal fluid samples in a case series of people with human immunodeficiency virus and Chagas disease. We identify different infecting T. cruzi populations, highlighting the usefulness of real-time polymerase chain reaction for Chagas disease reactivation diagnosis and evaluation of treatment response.


2-Substituted-4-methoxybenzimidazole-based PDE4 inhibitors.
A new family of PDE4 inhibitors based on a benzimidazole framework is described. Several of these compounds are orally bioavailable and show efficacy in in vivo models of inflammatory disease.


Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism.
An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with differences in the plasma levels of ACE as well as with myocardial infarction, cardiomyopathy, left ventricular hypertrophy, and coronary artery disease. We determined the cardiac ACE activity and the ACE genotype in 71 subjects who died of noncardiac disorders. Cardiac ACE activity was significantly higher (P < .01) in subjects with the ACE DD genotype (12.7 +/- 1.9 mU/g wet wt) compared with subjects with the ID (8.7 +/- 0.8 mU/g) and the II (9.1 +/- 1.0 mU/g) genotypes. This difference was independent of sex, age, and the time required for tissue collection. Cardiac ACE activity is highest in subjects with the DD genotype. Elevated cardiac ACE activity in these subjects may result in increased cardiac angiotensin II levels, and this may be a mechanism underlying the reported association between the ACE deletion polymorphism and the increased risk for several cardiovascular disorders.


Systemic dissemination as a result of oral infection in individuals 50 years of age and older.
The oral pathosis caused by systemic disorders in middle-aged and elderly adults has been the focus of many publications in recent years. The intraoral soft and hard tissue changes associated with systemic disorders, medications, chemotherapy, and radiation treatment have been well-investigated and -documented. Far less attention has been paid to the role of oral infection as the etiology of systemic disorders. A literature review (1980-1994) is provided here focusing on well-documented cases in which systemic disorders were caused by oral foci of infections. This paper attempts to raise the level of awareness of practitioners in considering possible systemic complications caused by oral infection. It also emphasizes the need for further longitudinal studies in this field involving healthy and medically compromised elderly individuals.


Two-electrode biopotential amplifier with current-driven inputs.
A circuit was developed for a differential two-electrode biopotential amplifier. Current sources at the amplifier inputs were controlled by the common-mode voltage. This principle is well known in telephony for interfacing the telephone line with analogue-type phones. A low impedance of about 1 k(ohm) was obtained between each input and the common point of the circuit. The differential input impedance of 60 M(ohm) was obtained with the use of precision resistors. Considerable reduction in the common-mode voltages of more than 200 times resulted. The circuit can be useful for biosignal acquisition from subjects in areas of very high electromagnetic fields, where high common-mode voltages could saturate the input amplifier stages.


Upregulated expression of NOP2 predicts worse prognosis of gastric adenocarcinoma by promoting tumor growth.
: NOP2 nucleolar protein plays a crucial role in early embryo development and cell proliferation. The role of NOP2 in human gastric adenocarcinoma has not been elucidated. In the present study, we aimed to examine the expression levels of NOP2 and dissected whether NOP2 expression was associated with aggressive clinicopathological outcomes of patients with gastric adenocarcinoma. : Clinicopathological analysis was performed in patients with gastric adenocarcinoma. Expression of NOP2 was tested by immunohistochemistry staining and quantitative RT-PCR. The prognostic role of NOP2 in gastric adenocarcinoma patients was assessed by univariate and multivariate analysis. The effect of NOP2 on cell proliferation was examined through cellular experiments and mice models. : NOP2 expression was elevated in gastric adenocarcinoma tissues compared to normal gastric tissues. High expression of NOP2 was significantly correlated with tumor size, invasion depth, and lymph node metastasis. Moreover, patients with high NOP2 expression had poorer overall survival, and NOP2 was identified as an independent prognosis factor. Using the gastric adenocarcinoma cells, we found that NOP2 can promote tumor cell proliferation both in vitro and in vivo. : Overexpression of NOP2 significantly correlates with a poorer prognosis of gastric adenocarcinoma patients and suggested the potential of NOP2, which may serve as a novel prognostic biomarker in gastric adenocarcinoma.


Entry into and release of solvents by Escherichia coli in an organic-aqueous two-liquid-phase system and substrate specificity of the AcrAB-TolC solvent-extruding pump.
Growth of Escherichia coli is inhibited upon exposure to a large volume of a harmful solvent, and there is an inverse correlation between the degree of inhibition and the log P(OW) of the solvent, where P(OW) is the partition coefficient measured for the partition equilibrium established between the n-octanol and water phases. The AcrAB-TolC efflux pump system is involved in maintaining intrinsic solvent resistance. We inspected the solvent resistance of delta acrAB and/or delta tolC mutants in the presence of a large volume of solvent. Both mutants were hypersensitive to weakly harmful solvents, such as nonane (log P(OW) = 5.5). The delta tolC mutant was more sensitive to nonane than the delta acrAB mutant. The solvent entered the E. coli cells rapidly. Entry of solvents with a log P(OW) higher than 4.4 was retarded in the parent cells, and the intracellular levels of these solvents were maintained at low levels. The delta tolC mutant accumulated n-nonane or decane (log P(OW) = 6. 0) more abundantly than the parent or the delta acrAB mutant. The AcrAB-TolC complex likely extrudes solvents with a log P(OW) in the range of 3.4 to 6.0 through a first-order reaction. The most favorable substrates for the efflux system were considered to be octane, heptane, and n-hexane.


Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry.
Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas.


Origins of aberrant DNA methylation in acute myeloid leukemia.
Aberrant DNA methylation patterns are a characteristic feature of cancer including myeloid malignancies such as acute myeloid leukemia (AML). The mechanisms behind aberrant DNA methylation have long remained obscure. New genome-wide studies have elucidated the genome and epigenome of solid tumors and AML. Molecular subtypes of AML were found to exhibit highly distinct DNA methylation profiles. Clonal evolution patterns of AML were recently dissected and might shape epigenetic dysregulation. Also, recurrent mutations in epigenetic modifying enzymes were identified in AML and linked to distinct DNA methylation signatures. The genetic background, thus, takes center stage as a driver of epigenetic dysregulation in AML. First mechanistic insights into the dysregulation of DNA methylation by recurrent mutations have already been gained. Other studies suggest that epigenomic plasticity and aging-associated changes in DNA methylation also contribute extensively to aberrant DNA methylation in cancer. Epigenetic dysregulation, therefore, seems to also occur independently of the genetic background. Furthermore, global changes in chromatin conformation and nuclear organization have also been proposed as potential contributors to aberrant DNA methylation. This review will summarize and discuss current concepts regarding the mechanisms behind aberrant DNA methylation in cancer and specifically AML.


Improved functional recovery of the isolated rat heart after 24 hours of hypothermic arrest with a stable prostacyclin analogue (ZK 36 374).
Prostacyclin (PGI2) can protect the heart against ischemia, i.e. it can reduce myocardial damage [9, 10]. PGI2 protects the myocardium in vivo by preventing platelets from clumping and by dispersing preformed platelet aggregates [1,14]. However, also in the absence of platelets, PGI2 was shown to protect the myocardium against ischemia at concentrations that did not affect smooth muscle tone in the vessel wall [2]. This protective effect of PGI2 in vitro might be related to a stabilization of cell membranes in adrenergic nerve endings and hence to the prevention of ischemia-induced catecholamine release [13]. The instability of PGI2, both in vitro and in vivo, limits its application during long ischemic periods. Recently, a stable prostacyclin analogue, ZK 36 374, was demonstrated to have several prostacyclin-mimetic activities, both in vitro and in vivo [11,12]. In this communication we report upon the beneficial effect of this stable prostacyclin analogue at a low concentration (4 nM) on the extent of ischemic damage, on the recovery of myocardial function and on the occurrence of arrhythmias in the isolated rat heart after 24 h hypothermic cardiac arrest.


The transcriptional response of Arcobacter butzleri to cold shock.
Arcobacter (A.) butzleri is an emerging zoonotic pathogen associated with gastrointestinal diseases, such as abdominal cramps and diarrhea, and is widely detected in animals, showing a high prevalence in poultry and seafood. The survival and adaptation of A. butzleri to cold temperatures remains poorly studied, although it might be of interest for food safety considerations. To address this, growth patterns of eight A. butzleri isolates were determined at 8 °C for 28 days. A. butzleri isolates showed strain-dependent behavior: six isolates were unculturable after day 18, one exhibited declining but detectable cell counts until day 28 and one grew to the stationary phase level. Out of 13 A. butzleri cold shock-related genes homologous to Escherichia coli, 10 were up-regulated in response to a temperature downshift to 8 °C, as demonstrated by reverse transcription-quantitative PCR. Additionally, we compared these data with the cold-shock response in E. coli. Overall, we provide a deeper insight into the environmental adaptation capacities of A. butzleri, which we find shares similarities with the E. coli cold-shock response.


The impact of a liberalisation law on legally induced abortion hospitalisations.
Legal abortion based purely in maternal option without fetal/maternal pathology was liberalised in Portugal in 2007 and since then abortion rates have increased substantially. The aim of this paper was to study the impact of the liberalisation of abortion by maternal request on total legal abortion related hospitalisation trends. We considered hospitalisations of legal abortion (ICD-9-CM codes 635.x) with discharges from 2000 to 2014. Data was obtained from a Portuguese administrative database, which contains all registered public hospitalisations in mainland Portugal. Performed legal abortions during the same period were obtained from INE (National Statistics Institute). Hospitalisations per abortion were calculated by dividing the number of legal abortions hospitalisations per the number of legal abortions, mean ages, number of hospitalisations per age group, complications, admission type and length of stay were also analysed, throughout the study period. Hospitalisations rose during the study period, (from 618 episodes in 2000 to 1,259 in 2014, with a peak of 1,603 in 2010). Since the liberalisation law was passed there was a significant decrease in the number of hospitalisations per abortion: from 1.07 in 2000 to 0.11 in 2014 (p<0.001). Furthermore, the mean age maintained stable since liberalisation (30.8 years before 2007 and 31.0 after). Abortion related hospitalisations are more frequent in women aged 25-39. A significant decrease from the emergent to the scheduled type of admission occurred from 2000 to 2014 (from 83.5% to 56.7% of emergent admissions) (p<0.001). Complications remained stable between 2000 and 2014 and delayed or excessive haemorrhage was the most frequent (4.6%). Since the liberalisation, hospitalisations per abortion have decreased, reflecting the major impact that the liberalisation of legal abortion by maternal request had on abortion trends nationwide. Before the liberalisation, each abortion led to approximately one hospitalisation while after the liberalisation this trend shifted to approximately 10% of the number of abortions. Legal abortion related hospitalisations are more frequent in women aged between 25 and 39 years old, an older age group when compared to the one registered in all cases of legal abortions, reflecting the differences between those hospitalised and those who are not. Our study shows the impact that legal abortion by maternal request liberalisation law can bring to abortion and to hospitalisation trends.


A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments.


Increased apoptosis and myocyte enlargement with decreased cardiac mass; distinctive features of the aging male, but not female, monkey heart.
We studied gender-specific changes in aging cardiomyopathy in a primate model, Macaca fascicularis, free of the major human diseases, complicating the interpretation of data specific to aging in humans. Left ventricular (LV) weight/body weight decreased, p<0.05, in old males but did not change in old females. However, despite the decrease in LV weight, mean myocyte cross-sectional area in the old males increased by 51%. This increase in myocyte size was not uniform in old males, i.e., it was manifest in only 20-30% of all the myocytes from old males. In old males there was a 4-fold increase in frequency of myocyte apoptosis without any increase in proliferation-capable myocytes assessed by Ki-67 expression. Apoptosis was unchanged in old female monkey hearts, whereas the frequency of myocytes expressing Ki-67 declined 90%. These results, opposite to findings from rodent studies, indicate distinct differences in which male and female monkeys maintain functional heart mass during aging. The old male hearts demonstrated increased apoptosis, which more than offset the myocyte hypertrophy. Interestingly, the hypertrophy was not uniform and there was no significant increase in myocyte proliferation.