Occupational exposure to chlorinated and petroleum solvents and mycosis fungoides.
To evaluate the potential association between occupational exposure to chlorinated and petroleum solvents and mycosis fungoides (MF). A questionnaire on lifetime job history was administered to 100 patients diagnosed with MF and 2846 controls. Odds ratios (ORs) were calculated as the measure of the association between exposure to each specific solvent and MF. In the total sample and in men, cases and controls did not differ in relation to exposure to any of the solvents studied. In women, an association with MF was seen for the highest level of estimated exposure to perchloroethylene (OR = 11.38; 95% confidence interval: 1.04 to 124.85) and for exposure less than the median to kerosene/fuel/gasoil (OR = 8.53; 95% confidence interval: 1.11 to 65.62). These results do not provide conclusive evidence that exposure to solvents may increase risk of MF because they were not found in men.


High Performance Clean Fracturing Fluid Using a New Tri-Cationic Surfactant.
In order to improve the heat resistance of current clean fracturing fluids, a novel cationic surfactant (VES-T), composed of three single-chains and a spacer group, was designed and synthesized as thickener for the fluids. Various performances of such VES-T fluid in the presence of NaSal were evaluated carefully. Study of the rheological properties demonstrated that the fluids with varying concentrations (3⁻5 wt %) of VES-T have excellent thermal stabilities under ultra-high temperatures ranging from 140 to 180 °C. Until now, this is the highest temperature that the VES fracturing fluid could bear. The VES-T/NaSal fluid exhibited good viscoelasticity and proppant-suspending capability, which was attributed to the three-dimensional network formed by entangled wormlike micelles. Furthermore, the VES fracturing fluids can be completely gel broken by standard brines within 2 h. Thus, the VES-T synthesized in this work has a good prospect for utilization during the development of ultra-high temperature reservoirs.


Aberrant expression patterns of genes involved in segregation of inner cell mass and trophectoderm lineages in bovine embryos derived from somatic cell nuclear transfer.
High rates of embryonic, fetal, or placental abnormalities have consistently been observed in bovine cloning. Segregation of inner cell mass (ICM) and trophectoderm (TE) lineages in early embryos is an important process for fetal and placental formation. In mouse embryos, differentiation of ICM and TE is regulated by various transcription factors, such as OCT-4, CDX2, and TEAD4, but molecular mechanisms that regulate differentiation in bovine embryos remain unknown. To clarify gene transcripts involved in segregation of ICM and TE lineages in bovine embryos, we examined the relative abundances of OCT-4, CDX2, TEAD4, GATA3, NANOG, and FGF4 transcripts in blastocyst embryos derived from in vitro fertilization (IVF). Furthermore, transcript levels of such genes in bovine embryos derived from somatic cell nuclear transfer (NT-SC) and in vivo (Vivo) were also compared. OCT-4, NANOG, and FGF4 transcript levels in IVF embryos were significantly higher in ICM than in TE. In contrast, the CDX2 transcript level was lower in ICM than in TE. In NT-SC embryos at the blastocyst stage, transcript levels of all genes except CDX2 were lower than that in Vivo embryos. In the elongated stage, expression levels of the six genes did not differ between NT-SC and Vivo embryos. We observed aberrant expression patterns of various genes involved in segregation of ICM and TE lineages in bovine NT-SC embryos. These results raise the possibility that abnormalities in the cloned fetus and placenta are related to the aberrant expression of genes involved in segregation and differentiation process in the early developmental stage.


Bax translocates to mitochondria of heart cells during simulated ischaemia: involvement of AMP-activated and p38 mitogen-activated protein kinases.
The cytosolic protein Bax plays a key role in apoptosis by migrating to mitochondria and releasing proapoptotic proteins from the mitochondrial intermembrane space. The present study investigates the movement of Bax in isolated rat neonatal cardiomyocytes subjected to simulated ischaemia (minus glucose, plus cyanide), using green fluorescent protein-tagged Bax as a means of imaging Bax movements. Simulated ischaemia induced Bax translocation from the cytosol to mitochondria, commencing within 20 min of simulated ischaemia and progressing for several hours. Under the same conditions, there was an increase in the active, phosphorylated forms of p38 MAPK (mitogen-activated protein kinase) and AMPK (AMP-activated protein kinase). The AMPK activators AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and metformin also stimulated Bax translocation. Inhibition of p38 MAPK with SB203580 attenuated the phosphorylation of the downstream substrates, MAPK-activated protein kinases 2 and 3, but not that of the upstream MAPK kinase 3, nor of AMPK. Under all conditions (ischaemia, AICAR and metformin), SB203580 blocked Bax translocation completely. It is concluded that Bax translocation to mitochondria is an early step in ischaemia and that it occurs in response to activation of p38 MAPK downstream of AMPK.


[Effect of superoxide dismutase on membrane fluidity and functions of lymphocytes in traumatized mice].
Effect of superoxide dismutase (SOD) on membrane fluidity and functions of lymphocytes in traumatized mice was studied. The results showed that in vivo administration of SOD (10,000 U/kg.d, from 0 to 3 days posttrauma) could significantly decrease malondialdehyde (MDA) contents in serum, lymphatic tissues from spleen, thymus, mesenteric lymph nodes and T cells plasmalemma, mitochondria, microsome, restore decreased T lymphocytes and T cells in traumatized mice, elevate membrane fluidity of lymphocytes transformation (TLT), reduce interleukin 2 (IL-2) production, supprssed IL-2 receptor (IL-2R) expression and depress IL-2 mediated lymphocyte proliferation response (IL 2MLPR) after trauma in various degress. It is suggested that SOD may protect lymphocytes post trauma from damage of oxygen free radical, and elevate lymphocytes functions.


Educating the delivery of bad news in medicine: Preceptorship versus simulation.
Simulation experiences have begun to replace traditional education models of teaching the skill of bad news delivery in medical education. The tiered apprenticeship model of medical education emphasizes experiential learning. Studies have described a lack of support in bad news delivery and inadequacy of training in this important clinical skill as well as poor familial comprehension and dissatisfaction on the part of physicians in training regarding the resident delivery of bad news. Many residency training programs lacked a formalized training curriculum in the delivery of bad news. Simulation teaching experiences may address these noted clinical deficits in the delivery of bad news to patients and their families. Unique experiences can be role-played with this educational technique to simulate perceived learner deficits. A variety of scenarios can be constructed within the framework of the simulation training method to address specific cultural and religious responses to bad news in the medical setting. Even potentially explosive and violent scenarios can be role-played in order to prepare physicians for these rare and difficult situations. While simulation experiences cannot supplant the model of positive, real-life clinical teaching in the delivery of bad news, simulation of clinical scenarios with scripting, self-reflection, and peer-to-peer feedback can be powerful educational tools. Simulation training can help to develop the skills needed to effectively and empathetically deliver bad news to patients and families in medical practice.


Use of an infectious bronchitis virus and Escherichia coli model infection to assess the ability to vaccinate successfully against infectious bronchitis in the presence of maternally-derived immunity.
Using as challenge, a mixed infectious bronchitis virus (IBV) and Escherichia coli infection, specified pathogen-free (SPF) chicks and chicks with maternally-derived immunity (MDI) could be protected by a single intra-nasal vaccination with a live-attenuated IB vaccine given at 1 day of age against intranasal challenge with either a homologous or a heterologous IBV strain for at least 7 weeks. However, protection was incomplete if challenge occurred within approximately 14 days of vaccination. Vaccination at 7 or 14 days of age was also equally effective in protecting both SPF and MDI chicks for at least 4 weeks. The value of using in challenge studies a mixed IBV and E. coli infection, which takes account of the response of the intact chicken to challenge, is discussed.


T cell receptor Vbeta repertoire of tumour-infiltrating lymphocytes in oral squamous-cell carcinoma.
Oral squamous cell carcinoma (OSCC) are frequently infiltrated by tumour infiltrating lymphocytes (TILs) which may demonstrate specific anti-tumour cytotoxicity. We have used a panel of family-specific primers in reverse-transcriptase (RT)-polymerase chain reactions (PCR) to determine the TCR Vbeta repertoire of TILs in the primary and metastatic tumours in patients with OSCC. We observed a diverse and heterogenous usage of TCR Vbeta genes by TILs in the primary tumours, a scenario not unlike normal oral mucosal lymphocytes. In one patient with a longstanding history of OSCC, the repertoire was restricted. Restricted TCR Vbeta gene usage also occurred in TILs of metastatic tumours. Within individual patients, discrepancies of TCR Vbeta gene usage were also observed between TILs in the primary OSCC and those in metastatic lymph nodes. Work is ongoing to determine the clonality and functional significance of these TILs.


Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study.
Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.


Impact of Tumbling Process on the Toughness and Structure of Raw Beef Meat Pieces.
Tenderness is a major factor in consumer perception and acceptability of beef meat. Here we used a laboratory tumbling simulator to investigate the effectiveness of the tumbling process in reducing the toughness of raw beef cuts. Twelve Semitendinosus beef muscles from cows were tumbled according to four programs: T1 (2500 consecutive compression cycles (CC), for about 3 h), T2 (6000 CC, about 7.5 h), T3 (9500 CC, about 12 h), and T4 (13,000 CC, about 16 h). The effect of tumbling on the toughness of raw meat was assessed using compression tests (stresses measured at 20% and 80% of deformation ratios) and microscopic observations made at the periphery and centre of meat samples, and compared against non-tumbled controls. Longer tumbling times significantly reduced the stresses measured at 20% and 80% compression rates, which reflected the toughness of muscle fibres and connective tissue, respectively. At the microscopic level, longer tumbling times led to reduced extracellular spaces, increased degradation of muscle structure, and the emergence of amorphous zones. A 12-h tumbling protocol ultimately makes the best compromise between the process time demand and toughness reduction in beef Semitendinosus meat pieces.


[Increased radiation reactions of the efferent urinary system following gynecologic radiation therapy. Incidence, prevention and therapy].
Basing on the newer literature and own experiences a survey is given concerning radiation reactions occasionally to be seen with kidney, ureter, urinary bladder and urethra in connection with the radiation therapy in gynecology. Hints are given to prophylaxis and therapy of these radiation reactions with special emphasis of the treatment with instillation solutions in case of raised reactions of the urinary bladder.


Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events.
It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of <0.1 Gy occurred at non-significant levels. The mutation spectrum in HPRT-deficient mutants revealed that the type of mutations induced by low-dose exposures was similar to that seen in spontaneous mutants. An apparent change in mutation type was observed for mutants induced by doses of >0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events.


Aldosterone stimulation by angiotensin II : influence of gender, plasma renin, and familial resemblance.
The aldosterone response to infused angiotensin II (Ang II) in patients receiving a low-salt diet has been described as an important phenotype for genetic studies on human hypertension. The objectives of the present study were to determine the parameters that influence this intermediate phenotype as a quantitative trait and to assess the importance of its familial resemblance in hypertensive sibling pairs. Two hundred one white hypertensive subjects (95 families: 84 pairs and 11 trios) were selected in 3 centers. The patients followed the same protocol, which included a 4-week withdrawal period of antihypertensive therapy, a 1-week period on a low-salt diet, and a 30-minute infusion of Ang II. The increase in the aldosterone level was greater in women than in men (29.1+/-16.2 versus 18.2+/-9.6 ng/dL, P<0.0001). A strong relationship was found with age (r=-0.54, P<10(-4)) and plasma renin activity (r=0.32, P<10(-4)) in women but not in men. Weak correlations of the aldosterone response to Ang II were observed for the whole set of sibling pairs (r=0.11, NS). Conversely, strong sibling correlations were found among brother-brother pairs (r=0.40, n=36) and among sister-sister pairs as soon as age or menopausal status was considered. Similar results were obtained when the Ang I-aldosterone response was analyzed as a qualitative trait (kappa=0. 35, P<0.008 in brother-brother pairs). We conclude that age, gender, and plasma renin are strong determinants of the aldosterone response to Ang II, with strong sibling correlations in men and postmenopausal women. These relationships will have to be considered in future linkage and association studies.


A multi-view deep convolutional neural networks for lung nodule segmentation.
We present a multi-view convolutional neural networks (MV-CNN) for lung nodule segmentation. The MV-CNN specialized in capturing a diverse set of nodule-sensitive features from axial, coronal and sagittal views in CT images simultaneously. The proposed network architecture consists of three CNN branches, where each branch includes seven stacked layers and takes multi-scale nodule patches as input. The three CNN branches are then integrated with a fully connected layer to predict whether the patch center voxel belongs to the nodule. The proposed method has been evaluated on 893 nodules from the public LIDC-IDRI dataset, where ground-truth annotations and CT imaging data were provided. We showed that MV-CNN demonstrated encouraging performance for segmenting various type of nodules including juxta-pleural, cavitary, and non-solid nodules, achieving an average dice similarity coefficient (DSC) of 77.67% and average surface distance (ASD) of 0.24, outperforming conventional image segmentation approaches.


Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin.
Thiolactomycin (TLM), a natural product thiolactone antibiotic produced by species of Nocardia and Streptomyces, is an inhibitor of the beta-ketoacyl-acyl carrier protein synthase (KAS) enzymes in the bacterial fatty acid synthase pathway. Using enzyme kinetics and direct binding studies, TLM has been shown to bind preferentially to the acyl-enzyme intermediates of the KASI and KASII enzymes from Mycobacterium tuberculosis and Escherichia coli. These studies, which utilized acyl-enzyme mimics in which the active site cysteine was replaced by a glutamine, also revealed that TLM is a slow onset inhibitor of the KASI enzymes KasA and ecFabB but not of the KASII enzymes KasB and ecFabF. The differential affinity of TLM for the acyl-KAS enzymes is proposed to result from structural change involving the movement of helices alpha5 and alpha6 that prepare the enzyme to bind malonyl-AcpM or TLM and that is initiated by formation of hydrogen bonds between the acyl-enzyme thioester and the oxyanion hole. The finding that TLM is a slow onset inhibitor of ecFabB supports the proposal that the long residence time of TLM on the ecFabB homologues in Serratia marcescens and Klebsiella pneumonia is an important factor for the in vivo antibacterial activity of TLM against these two organisms despite the fact that the in vitro MIC values are only 100-200 microg/ml. The mechanistic data on the interaction of TLM with KasA will provide an important foundation for the rational development of high affinity KasA inhibitors based on the thiolactone skeleton.


Therapeutic Effects of HLA-G5 Overexpressing hAMSCs on aGVHD After Allo-HSCT: Involving in the Gut Microbiota at the Intestinal Barrier.
Acute graft-versus-host disease (aGVHD) initiated by intestinal barrier dysfunction and gut microbiota dysbiosis, remains one of the main obstacles for patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) to achieve good prognosis. Studies have suggested that mesenchymal stem cells (MSCs) can suppress immune responses and reduce inflammation, and human leukocyte antigen-G5 (HLA-G5) plays an important role in the immunomodulatory effects of MSCs, but very little is known about the potential mechanisms in aGVHD. Thus, we explored the effect of HLA-G5 on the immunosuppressive properties of human amnion MSCs (hAMSCs) and demonstrated its mechanism related to the gut microbiota at the intestinal barrier in aGVHD. Patients undergoing allo-HSCT were enrolled to detect the levels of plasma-soluble HLA-G (sHLA-G) and regulatory T cells (Tregs). Humanized aGVHD mouse models were established and treated with hAMSCs or HLA-G5 overexpressing hAMSCs (ov-HLA-G5-hAMSCs) to explore the mechanism of HLA-G5 mediated immunosuppressive properties of hAMSCs and the effect of ov-HLA-G5-hAMSCs on the gut microbiota at the intestinal barrier in aGVHD. The plasma levels of sHLA-G on day +30 after allo-HSCT in aGVHD patients were lower than those in patients without aGVHD, and the sHLA-G levels were positively correlated with Tregs percentages. ov-HLA-G5-hAMSCs had the potential to inhibit the expansion of CD3+CD4+ T and CD3+CD8+ T cells and promote Tregs differentiation, suppress proinflammatory cytokine secretion but promote anti-inflammatory cytokines release. Besides, ov-HLA-G5-hAMSCs also could reverse the intestinal barrier dysfunction and gut microbiota dysbiosis in aGVHD. We demonstrated that HLA-G might work with Tregs to create a regulatory network together to reduce the occurrence of aGVHD. HLA-G5 mediated hAMSCs to exert higher immunosuppressive properties in vivo and reverse the immune imbalance caused by T lymphocytes and cytokines. Furthermore, HLA-G5 overexpressing hAMSCs could restore gut microbiota and intestinal barriers, thereby ameliorating aGVHD.


Role of p38 MAPK in the regulation of apoptosis signaling induced by TNF-alpha in differentiated PC12 cells.
TNF-alpha elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-alpha induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-alpha. TNF-alpha initiates various signal transduction pathways leading to the activation of the caspase family, NF-subk;B, Jun N-terminal kinase, and p38 MAPK via the death domain that contains the TNF-alpha receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-alpha. This implies that the induction of anti-apoptotic genes for survival by TNF-alpha may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-alpha. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-alpha in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-alpha slowly increased and lasted several hours in the PC12 cell and DRG neuron. This prolonged and slow phosphorylation of p38 MAPK was distinct from other non-neuronal cells. The specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-alpha in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in response to TNF-alpha in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.


Cyanidin suppresses ultraviolet B-induced COX-2 expression in epidermal cells by targeting MKK4, MEK1, and Raf-1.
Skin cancer is the most frequently diagnosed cancer in the United States. Ultraviolet B (UVB) rays (wavelength: 280-320nm) play a pivotal role in the development of skin cancer by inducing the expression of inflammatory proteins such as cyclooxygenase-2 (COX-2). Cyanidin, the most plentiful of the plant pigments known as anthocyanidins, is a potent chemopreventive agent. In the present study, we examined the molecular mechanisms underlying the chemopreventive activity of cyanidin and identified its molecular targets. Cyanidin inhibited UVB-induced COX-2 expression and prostaglandin E(2) secretion in the epidermal skin cell line JB6 P+ by suppressing the transactivation of nuclear factor-kappaB and activator protein-1 which are well-known transcription factors regulated by mitogen-activated protein kinase. Cyanidin markedly inhibited the phosphorylation of JNK1/2, ERK1/2, and MEK1/2 than the of MKK4 and Raf-1, two upstream kinases of JNK1/2, ERK1/2, and MEK1/2. Cyanidin significantly suppressed the activities of MKK4, MEK1, and Raf-1 through direct binding. Transient transfection of a small interfering RNA specific for MKK4 inhibited the UVB-induced expression of COX-2 in JB6 P+ cells, as did the expression of a dominant-negative ERK2 mutant. We conclude that MKK4, MEK1, and Raf-1 are targets of cyanidin for the suppression of UVB-induced COX-2 expression.


Survival motor neuron: motor neuron insurance for a whole lifespan?
The SMN (survival motor neuron) gene plays an important role in ontogenesis and its dysfunction leads to immatu-rity of skeletal muscles and motor neurons in the spinal cord. As a result of SMN mutations the affected cells die and clinical symptoms of spinal muscular atrophy (SMA) develop. Physiologically, SMN together with gemins is part of a multiprotein complex of particular importance to motor neuron development. Since the SMN gene is necessary for normal motor neuron maturity, a question arises whether its expression is preserved in postnatal life or finishes with the end of ontogenesis. To answer this question we examined expression of SMN and gemins 2, 3 and 4 in spinal cords of Wistar rats at age 1-350 days using immunofluorescence and immunohistochemical methods. In the examined animals expression of SMN appeared in neurons in 20-day old rats and increased with animal age. In rats aged 30-350 days SMN immunoreactivity was similar in all the examined animals. The same phenomenon was observed in assessment of gemin expression. Our study revealed that in rat spinal cord expression of SMN and gemins 2, 3 and 4 is present through a whole animal lifespan and not only in motor but also in sensory and autonomic neurons.


The Impact of Dental Care in Head and Neck Cancer Outcomes: A Systematic Review and Meta-Analysis.
The objective of this study was to perform a systematic review and meta-analysis to determine the impact of dental care on head and neck (H&N) cancer survival. A comprehensive literature search was performed using PubMed, MEDLINE, and CINAHL to find all relevant studies from the date of inception to March 2020. Systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and meta-analysis was performed using the random effects logistic regression model. Primary outcomes of interest were 5-year survival and hazard ratios comparing survival between dental care subgroups. H&N cancer survival rates strongly correlate with dental care adherence. Patients with good dental care had significantly better survival than patients with poor dental care (HR = 0.67, 95% CI: 0.55-0.83), with similar improved survival among patients with moderate versus poor dental care (HR = 0.67, 95% CI: 0.57-0.80). In addition, patients with good dental care had significantly decreased mortality than those with moderate dental care (HR = 0.81, 95% CI: 0.69-0.96), indicating an exposure-response gradient. For patients with H&N cancer, survival is significantly higher in those who receive recommended dental care compared with those who do not. NA Laryngoscope, 132:45-52, 2022.


Management of continuous venous gas emboli during extracorporeal life support utilizing the Kolobow gas trap.
Extracorporeal life support (ECLS) with a roller pump system uses a closed cardiopulmonary bypass (CPB) circuit not equipped with a venous reservoir. Hence, gas emboli cannot escape the ECLS circuit, predisposing to clot formation, membrane failure and potential gas embolism. Rarely, some patients may develop a continuous release of gas into the venous circulation from multiple sources. Two pediatric ECLS cases are presented with continuous venous gas embolism. A 'gas trap' was devised by creating a column of fluid erected vertically on the venous line. This allowed gas to rise within the column, separating it from the ECLS circuit, thus, preventing gas from lodging in the membrane.


Temazepam clearance unaltered in cirrhosis.
The kinetics of a single oral dose of the benzodiazepine hypnotic temazepam was evaluated in nine patients with biopsy-proven cirrhosis and in seven healthy controls matched for age and sex. Peak serum temazepam concentrations were reached later in cirrhotics than in controls (2.9 versus 0.6 h after dosage; p less than 0.05), indicating slower temazepam absorption in patients with cirrhosis. Temazepam volume of distribution was smaller in cirrhotics compared to controls, and elimination half-life shorter (10.6 versus 14.6 h). However, these differences were not significant. There were no significant differences between cirrhotics and controls in clearance of total temazepam (1.03 versus 1.03 ml/min/kg), clearance of unbound temazepam (27 versus 31 ml/min/kg), or free fraction in serum (3.9 versus 3.5% unbound). In two cirrhotic patients who received 20 mg of temazepam daily for 8 days, the extent of accumulation was consistent with the dosage interval relative to the elimination half-life, and was similar to the accumulation profile in healthy volunteers. Thus the onset of temazepam hypnotic activity may be delayed in cirrhotic patients, but the rate of elimination and the extent of accumulation are not altered compared to healthy persons of similar age and sex.


Human sexual intercourse.
The comprehensive therapist needs to view human sexual intercourse comprehensively to avoid its hazards and to promote its benefits for all patients.


Hepatic cerebrospinal fluid pseudocyst: a case report and review of the literature.
An abdominal pseudocyst is a rare, but important complication in patients with a ventriculo-peritoneal (VP) shunt insertion. Several predisposing factors for this complication have been suggested, including infection, obstruction or dislodgement, but the pathophysiology is still unknown. However, the abdominal inflammatory process is accepted widely as a hypothesis for the formation of an abdominal pseudocyst. In this study, we report the case of a 21-year-old male that presented with a high-grade fever, poor appetite, shortness of breath and unconsciousness 1 week after receiving a VP shunt insertion for obstructive hydrocephalus. Ultrasonography and computed tomographic scans of the abdomen revealed a well-defined large hepatic cyst surrounding the peritoneal tube of the VP shunt. A hepatic cerebrospinal fluid (CSF) cyst was diagnosed and Staphylococcus epidermis was cultured via CSF. After externalization of the VP shunt and adequate antibiotic treatment, the hepatic cyst was resolved. There was no recurrence observed in the regular follow up.


[Intermittent versus continuous renal replacement techniques: pro intermittent].
After an introduction that summarizes the new definitions and risk classification of acute kidney injury, along with the consequences on its epidemiology, available evidence in the literature is reviewed in order to compare intermittent and continuous renal replacement therapy in terms of survival, renal function recovery, hemodynamic stability, transferences between the different techniques and major complications.


Regulation of angiogenesis and matrix remodeling by localized, matrix-mediated antisense gene delivery.
Implantation of biomaterials, such as glucose sensors, leads to the formation of a poorly vascularized collagenous capsule that can lead to implant failure. This process, known as the foreign body reaction (FBR), develops in response to almost all biomaterials and consists of overlapping phases similar to those in wound healing. Implantation of porous biomaterials, such as polyvinyl alcohol sponges, also leads to granuloma formation within the interstices of the sponge prior to encapsulation by the FBR. We asked whether delivery of an antisense cDNA for the potent angiogenesis inhibitor thrombospondin (TSP) 2 would enhance blood vessel formation and alter collagen fibrillogenesis in the sponge granuloma and capsule. Collagen solutions were mixed with plasmid to generate gene-activated matrices (GAMs) and applied to biomaterials that were then implanted subcutaneously. Sustained expression of plasmid-encoded proteins was observed at 2 weeks and a month following implantation. In vivo delivery of plasmids, encoding either sense or antisense TSP2 cDNA, altered blood vessel formation and collagen deposition in TSP2-null and wild-type mice, respectively. Untreated implants, implanted next to GAM-treated implants, did not show exogenous gene expression and did not elicit altered responses, suggesting that gene delivery was limited to implant sites. This method of antisense DNA delivery has the potential to improve the performance and life span of implantable delivery devices and biosensors.


Health care when workers need it most: before and after entry into the Social Security Disability Insurance Program.
This study analyzed survey data on Social Security Disability Insurance (SSDI) beneficiaries during the six-year window surrounding SSDI entitlement to illustrate changes in characteristics, insurance status, and health care access. We found that SSDI beneficiaries were less likely to be insured than the general working-age population, even three years before SSDI entitlement, and their uninsurance rates remained high until the third year after SSDI entitlement. Health care access problems were reported frequently during all periods surrounding SSDI entitlement, and poverty rates increased markedly post-entitlement. The findings suggest that there are significant gaps in the safety net for disabled workers before, during, and after the transition to SSDI.


Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver.
Background: Humans are constantly exposed to low concentrations of 4-tert-octylphenol (OP). However, studies investigating the effects of low-dose OP on the liver are scarce, and the mechanism of these effects has not been thoroughly elucidated to date. Methods: Adult male institute of cancer research (ICR) mice were exposed to low-dose OP (0, 0.01 and 1 μg/kg/day) for 7 consecutive days. Weights of mice were recorded daily during the experiment. Blood serum levels of OP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and haematoxylin-eosin (HE) staining of the liver was performed. We applied an integrated metabolomic and enzyme gene expression analysis to investigate liver metabolic changes, and the gene expression of related metabolic enzymes was determined by real-time PCR and ELISA. Results: OP in blood serum was increased after OP exposure, while body weights of mice were unchanged. Liver weight and its organ coefficient were decreased significantly in the OP (1 μg/kg/day) group, but ALT and AST, as well as the HE staining results, were unchanged after OP treatment. The levels of cytidine, uridine, purine and N-acetylglutamine were increased significantly, and the level of vitamin B6 was decreased significantly in mice treated with OP (1 μg/kg/day). The mRNA and protein levels of Cda and Shmt1 were both increased significantly in OP (1 μg/kg/day)-treated mice. Conclusions: Through metabolomic analysis, our study firstly found that pyrimidine and purine synthesis were promoted and that N-acetylglutamine was upregulated after low-dose OP treatment, indicating that the treatment disturbed nucleic acid and amino acid metabolism in mice liver.


Photobiomodulation therapy for androgenetic alopecia: A clinician's guide to home-use devices cleared by the Federal Drug Administration.
The market for home-use photobiomodulation devices to treat androgenetic alopecia has rapidly expanded, and the Food and Drug Administration (FDA) has recently cleared many devices for this purpose. Patients increasingly seek the advice of dermatologists regarding the safety and efficacy of these hair loss treatments. The purpose of this guide was threefold: (1) to identify all home-use photobiomodulation therapy devices with FDA-clearance for treatment of androgenetic alopecia; (2) to review device design, features and existing clinical evidence; and (3) to discuss practical considerations of photobiomodulation therapy, including patient suitability, treatment goals, safety, and device selection. A search of the FDA 510(k) Premarket Notification database was conducted using product code "OAP" to identify all home-use devices that are FDA-cleared to treat androgenetic alopecia. Thirteen commercially available devices were identified and compared. Devices varied in shape, wavelength, light sources, technical features, price, and level of clinical evidence. To date, there are no head-to-head studies comparing the efficacy of these devices. Photobiomodulation therapy devices have an excellent safety profile and mounting evidence supporting their efficacy. However, long-term, high quality studies comparing these devices in diverse populations are lacking. As these devices become increasingly popular, dermatologists should be familiar with this treatment modality to add to their therapeutic armamentarium. AGA, androgenetic alopecia; FDA, Food and Drug Administration; IEC, International Electrotechnical Commission; LED, light-emitting diode; PBMT, photobiomodulation therapy.


Enhancement of burn wounds healing by platelet dressing.
The goal of this study was to evaluate the efficacy of platelet dressing in the treatment of burn wounds and compare its results with silver sulfadiazine dressing. Between 21 march 2011 to 21 September, 50 patients with burn injuries were selected by a randomized double-blind controlled trial. In order to eliminate the biological and personal variables among the various treated burn wounds, in the same patient, distal or proximal, lateral or medial part of burn wound were selected for dressing with platelet or silver sulfadiazine. All patients were designated for homologous component use. The dressing was repeated every day up to complete healing. The results indicated that treatment with platelet enhanced epithelialization and accelerate epithelialization and granulation tissue formation. Platelet dressing to be most significant in this respect compared with silver sulfadiazine dressing. It is concluded that topical application of platelet enhanced the wound healing process in burn patients.


Expression of microRNA-30c via lentivirus vector inhibits the proliferation and enhances the sensitivity of highly aggressive ccRCC Caki-1 cells to anticancer agents.
The clear cell renal cell carcinoma (ccRCC) is one of the most fatal urologic tumors, and the prognosis remains very poor for advanced or metastatic ccRCC. This study reveals the roles of microRNA (miR)-30c in regulating a highly aggressive ccRCC cell line proliferation by targeting MTA-1, which is a key mediator for human cancer metastasis. Results from quantitative real-time polymerase chain reaction showed that the expression of MTA-1, the target of miR-30c, was significantly higher in metastatic ccRCC specimens than in nonmetastatic ccRCC or nontumor specimens. Accordingly, endogenous miR-30c is at a much lower level in highly aggressive ccRCC Caki-1 cells than nontumor or ccRCC cell lines. Expression of miR-30c via lentivirus vector inhibits the proliferation, anchorage-independent growth, in vitro invasion or migration, or in vivo growth of Caki-1 cells by repressing MTA-1 protein expression. miR-30c also enhances the sensitivity of Caki-1 cells to anticancer agents, including sorafenib and paclitaxel. These data reveal the potential application of miR-30c and that its targeting gene, MTA-1, would be a potential target in metastatic ccRCC treatment.


Large Tricuspid Valve Myxoma in an Asymptomatic Patient with Uterine Myoma: An Uncommon Case.
Tricuspid valve myxomas are very uncommon tumors that could be found after the occurrence of pulmonary thromboembolism, symptomatic tricuspid obstruction, and right-sided heart failure. Herein, we describe a 42-year-old woman evaluated for an abdominal mass. In preoperative consultation, a tricuspid valve mass was detected in echocardiography. She underwent the removal of a benign uterine myoma and a myxoma of the tricuspid valve. Tricuspid valve myxomas constitute a scarce diagnosis. They could be asymptomatic, occurring in unusual locations and in association with benign tumors in other organs. Our patient was asymptomatic, underscoring the significance of the early diagnosis of this type of tumor to prevent further catastrophic events.


Erosion kinetics of hydrolytically degradable polymers.
Degradable polymers are beginning to play an increasing role as materials for environmental and medical applications. Understanding factors that control erosion, such as bond cleavage and the dissolution and diffusion of degradation products, will be critical to the future development of these materials. Erosion kinetics, photomicroscopy, and infrared spectroscopy were used to understand the erosion mechanism of two families of degradable polymers, polyanhydrides and polyesters. Polyanhydrides exhibit behavior more characteristic of surface erosion, whereas the polyesters exhibit bulk erosion patterns. Control of erosion times from a few days to several years can be achieved by a judicious choice of monomer units and bond selection.


Identification of dendritic antigen-presenting cells in the zebrafish.
In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DCs are of fundamental importance in orchestrating the mammalian immune response, their presence and function in nonmammalian vertebrates is largely unknown. Because teleosts possess one of the earliest recognizable adaptive immune systems, we sought to identify antigen-presenting cells (APCs) in the zebrafish to better understand the potential origins of DCs and their evolutionary relationship to lymphocytes. Here we present the identification and characterization of a zebrafish APC subset strongly resembling mammalian DCs. Rare DCs are present in various adult tissues, and can be enriched by their affinity for the lectin peanut agglutinin (PNA). We show that PNA(hi) myeloid cells possess the classical morphological features of mammalian DCs as revealed by histochemical and ultrastructural analyses, phagocytose-labeled bacterial preparations in vivo, and exhibit expression of genes associated with DC function and antigen presentation, including il12, MHC class II invariant chain iclp1, and csf1r. Importantly, we show that PNA(hi) cells can activate T lymphocytes in an antigen-dependent manner. Together, these studies suggest that the cellular constituents responsible for antigen presentation are remarkably conserved from teleosts to mammals, and indicate that the zebrafish may serve as a unique model to study the origin of APC subsets and their evolutionary role as the link between the innate and adaptive immune systems.


Salmonella , Campylobacter jejuni , and Yersinia enterocolitica in Raw Milk.
Raw milk samples collected from bulk tank trucks of milk suppliers in Wisconsin, Michigan, and Illinois were analyzed for Salmonella , Campylobacter jejuni , and Yersinia enterocolitica . Salmonella spp. were isolated from 32 (4.7%) of 678 samples, and C. jejuni was found in one (0.4%) of 237 samples. Although Y. enterocolitica was recovered from 114 (48.1%) of 237 samples, all isolates were environmental, non-virulent strains.


Distribution of soil viruses across China and their potential role in phosphorous metabolism.
Viruses are the most abundant biological entities on the planet and drive biogeochemical cycling on a global scale. Our understanding of biogeography of soil viruses and their ecological functions lags significantly behind that of Bacteria and Fungi. Here, a viromic approach was used to investigate the distribution and ecological functions of viruses from 19 soils across China. Soil viral community were clustered more significantly by geographical location than type of soil (agricultural and natural). Three clusters of viral communities were identified from North, Southeast and Southwest regions; these clusters differentiated using taxonomic composition and were mainly driven by geographic location and climate factors. A total of 972 viral populations (vOTUs) were detected spanning 23 viral families from the 19 viromes. Phylogenetic analyses of the phoH gene showed a remarkable diversity and the distribution of viral phoH genes was more dependent on the environment. Notably, five proteins involved in phosphorus (P) metabolism-related nucleotide synthesis functions, including dUTPase, MazG, PhoH, Thymidylate synthase complementing protein (Thy1), and Ribonucleoside reductase (RNR), were mainly identified in agricultural soils. The present work revealed that soil viral communities were distributed across China according to geographical location and climate factors. In addition, P metabolism genes encoded by these viruses probably drive the synthesis of nucleotides for their own genomes inside bacterial hosts, thereby affecting P cycling in the soil ecosystems.


Intimate Partner Violence, Maternal Sensitive Parenting Behaviors, and Children's Executive Functioning.
Despite knowledge that intimate partner violence (IPV) can negatively affect children's socioemotional and behavioral development, less is known about the impact of IPV on children's cognitive development, including whether it influences their executive functioning (EF). The goal of the current study was to address this gap in the literature, by examining the association between IPV that occurs early in life and EF at school entry. This study also allowed for the investigation of maternal sensitive parenting behaviors as a possible mediator of this relation. Using longitudinal data from a socioeconomically and racially diverse sample of families (n = 154), we investigated the association between IPV measured when children were 24, 30, and 36 months old and their EF when they were 60 months old. We also tested whether maternal sensitive parenting behaviors (measured when children were 24, 36, and 60 months old) mediated this association. Results indicate that, even after controlling for a number of family- and child-level covariates, IPV occurring early in children's lives was negatively associated with their EF at school entry. This relation was mediated by maternal sensitive parenting behaviors, such that higher levels of IPV were associated with lower levels of sensitive parenting behaviors, which in turn were positively associated with children's EF. These findings add to a limited body of literature that links IPV and children's cognitive functioning, and suggest that intervention efforts aimed at improving children's EF may want to simultaneously consider IPV and maternal sensitive parenting behaviors.


Muscarinic cholinergic receptors of rat lymphocytes: effect of antigen stimulation and local brain lesion.
Expression of muscarinic cholinergic receptors (m-AchR) on thymocytes and lymphocytes supports a hypothesis of direct interaction between autonomic innervation and the immune system. Using a muscarinic antagonist, [3H]quinuclidinyl benzilate ([3H]QNB), we revealed different characteristics of m-AchR expression in lymphocytes isolated from the spleen, peripheral blood or thymus of Wistar rats. To further explore the mechanisms controlling m-AchR expression in lymphocytes we have addressed two questions: (i) whether local brain lesions will affect [3H]QNB binding activity of lymphocytes and (ii) whether different antigens will alter m-AchR expression in lymphocytes. We report here that electrolytic lesions of the area hypothalamica anterior resulted in a significant increase in [3H]QNB-specific binding in thymocytes 7 days after neurosurgery. In contrast, local lesions of other hypothalamic structures (area preoptica medialis, area hypothalamica posterior) or sensomotor cortex did not affect m-AchR expression in thymocytes. No apparent changes of [3H]QNB-binding activity were found in lymphocytes isolated from rat spleen or peripheral blood after operation. Both T-cell-dependent (sheep red blood cells) and T-cell-independent (Vi antigen of Salmonella typhi) antigens induced a significant increase in [3H]QNB-specific binding in spleen lymphocytes while [3H]QNB-binding activity of peripheral blood lymphocytes did not change. A different pattern of lymphocyte m-AchR expression found in various lymphoid tissues after immunization or brain lesions suggests a local involvement of cholinergic mechanisms in neuroimmune interaction.


Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke.
Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals.


Cross-Validation of Single-Stage Treadmill Tests for Predicting Aerobic Fitness in Adolescents with Type I Diabetes.
Determining fitness is important when assessing adolescents with type 1 diabetes mellitus (T1DM). Submaximal tests estimate fitness, but none have been validated in this population. This study cross-validates the Ebbeling and Nemeth equations to predict fitness (VO2max (ml/kg/min)) in adolescents with T1DM. Adolescents with T1DM (n = 20) completed a maximal treadmill test using indirect calorimetry. Participants completed one 4-min stage between 2.0 and 4.5 mph and 5% grade (Ebbeling/Nemeth protocol). Speed and grade were then increased until exhaustion. Predicted VO2max was calculated using the Ebbeling and Nemeth equations and compared with observed VO2max using paired t tests. Pearson correlation coefficients, 95% confidence intervals, coefficients of determination (R²), and total error (TE) were calculated. The mean observed VO2max was 47.0 ml/kg/min (SD = 6.9); the Ebbeling and Nemeth mean predictions were 42.4 (SD = 9.4) and 43.5 ml/kg/min (SD = 6.9), respectively. Paired t tests resulted in statistically significant (p < .01) mean differences between observed and predicted VO2max for both predictions. The association between the Ebbeling prediction and observed VO2max was r = .90 (95% CI = 0.76, 0.96), R² = .81, and TE = 6.5 ml/kg/ min. The association between the Nemeth prediction and observed VO2max was r = .81 (95% CI = 0.57, 0.92), R² = .66, and TE = 5.6 ml/kg/min. The Nemeth submaximal treadmill protocol provides a better estimate of fitness than the Ebbeling in adolescents with T1DM.


Comparative analysis between convolutional neural network learned and engineered features: A case study on cardiac arrhythmia detection.
Atrial fibrillation (AF) is one of the most common cardiovascular problems, and its asymptomatic tendency makes AF detection challenging. Machine and deep learning methods are commonly used in AF detection. The purpose of this study was to evaluate the information provided by convolutional neural network (CNN) and random forest (RF) machine learning models for AF classification. We manually extracted 166 time-frequency domains and linear and nonlinear features to classify single-lead electrocardiograms (ECGs) as normal, AF, other, or noisy sinus rhythms. We selected a subset of 56 robust features using a genetic algorithm that was used in the RF model. In a separate study, a 1-dimensional, 12-layer CNN was designed on the raw ECG rhythms. Four features from the output layer and 128 features from the fully connected layer of CNN were explored independently for classification. The models were trained and internally validated on 8,528 ECGs and externally validated on a hidden dataset containing 3,658 ECGs. Next,we analyzed the correlation between engineered and CNN-learned features. An RF classifier trained with 56-engineered features resulted in an F1 score of 0.91, 0.78, and 0.72 for normal, AF, and other rhythms, respectively. However, an ensemble of support vector machine and the CNN model resulted in an F1 score of 0.92, 0.87, and 0.80, respectively. We explored various features and machine learning models to identify AF rhythms using short (9-61 seconds) single-lead ECG recordings. Our results showed that the proposed CNN model abstracted distinctive features for AF classification.


Pot, politics and the press--reflections on cannabis law reform in Western Australia.
Windows of opportunity for changing drug laws open infrequently and they often close without legislative change being affected. In this paper the author, who has been intimately involved in the process, describes how evidence-based recommendations to 'decriminalize' cannabis have recently been progressed through public debate and the political process to become law in Western Australia (WA). The Cannabis Control Bill 2003 passed the WA Parliament on 23 September. The Bill, the legislative backing behind the Cannabis Infringement Notice (CIN) Scheme, came into effect on 22 March 2004. This made WA the fourth Australian jurisdiction, after South Australia, the Australian Capital Territory and the Northern Territory, to adopt a prohibition with civil penalties scheme for minor cannabis offences. This paper describes some of the background to the scheme, the process by which it has become law, the main provisions of the scheme and its evaluation. It includes reflections on the role of politics and the press in the process. The process of implementation and evaluation are outlined by the author, foreshadowing an ongoing opportunity to understand the impact of the change in legislation.


Nano-pump based on exothermic surface reactions.
We present simulations indicating that it should be possible to construct a switchable nano-scale fluid pump, driven by exothermic surface reactions. Such a pump could, for instance, be controlled electro-chemically. In our simulations we explore a simple illustration of such a pump. We argue that the simplicity of the pump design could make it attractive for micro/nano-fluidics applications.


Motion controlled gait enhancing mobile shoe for rehabilitation.
Walking on a split-belt treadmill, which has two belts that can be run at different speeds, has been shown to improve walking patterns post-stroke. However, these improvements are only temporarily retained once individuals transition to walking over ground. We hypothesize that longer-lasting effects would be observed if the training occurred during natural walking over ground, as opposed to on a treadmill. In order to study such long-term effects, we have developed a mobile and portable device which can simulate the same gait altering movements experienced on a split-belt treadmill. The new motion controlled gait enhancing mobile shoe improves upon the previous version's drawbacks. This version of the GEMS has motion that is continuous, smooth, and regulated with on-board electronics. A vital component of this new design is the Archimedean spiral wheel shape that redirects the wearer's downward force into a horizontal backward motion. The design is passive and does not utilize any motors. Its motion is regulated only by a small magnetic particle brake. Further experimentation is needed to evaluate the long-term after-effects.


Physician-Modified Endograft With Inner Branches for the Treatment of Complex Aortic Urgencies.
To describe the use of physician-modified endograft (PMEG) with the exclusive use of inner branches or in combination with fenestrations for the urgent treatment of complex aortic aneurysms. We present two urgent cases. A patient with a 6.8 cm saccular juxtarenal aneurysm and another patient with a contained rupture of the thoracoabdominal aorta right above the celiac trunk (CT). In both cases, a Cook Zenith TX2 thoracic endograft was back-table modified, in the first case by adding three fenestrations and one inner branch for the left renal artery to improve sealing due to its partial involvement in the aneurysm and, in the second case, with the use of two inner branches for the CT and superior mesenteric artery. Both procedures were successful, with uneventful postoperative courses and complete aneurysm exclusion on postoperative CT angiography. Use of PMEGs with inner branches is feasible for urgent repair in complex aortic anatomy.


[Synthesis and properties of an affinity adsorbent for purifying neuraminidases of varying origins].
Neuraminidases (NA) from Clostridium perfringens, noncholera vibrios and influenza virus were purified by affinity chromatography on Sepharose coupled to para-aminophenyl oxamic acid. Adsorption was carried out at pH 5.5. The effect of elution conditions on purification of NA was studied. The use of the pH gradient enhances 10-fold the purification degree as compared with the pH shift-elution process, 90% of the activity being eluted from the column within a pH range from 6.0 to 6.6. According to the described procedure, electrophoretically homogeneous preparations of NA were obtained from noncholera vibrios and influenza virus.


Detection of abasic sites on individual DNA molecules using atomic force microscopy.
We have developed an atomic force microscopy-based method for detecting abasic sites (AP sites) on individual DNA molecules. By using uracil and uracil DNA glycosylase, we first prepared a 250-bp DNA template consisting of two AP sites at specific locations. We then detected the AP sites by marking them with biotinylated aldehyde-reactive probes and monomeric avidin. We demonstrate here that (i) the location of monomeric avidin bound on a single DNA molecule was detectable by atomic force microscopy; (ii) the observed location of avidin was in good agreement to the predicted AP sites at a few nanometer resolution; and (iii) by end-labeling the 5'-terminus of one DNA strand, the AP sites were determined without directional ambiguity. The technique described here will provide a sensitive way of locating AP sites and contribute to screen DNA damages from individual molecules.


Cross-cultural adaptation of the Brazilian version of the Athlete Sleep Behavior Questionnaire.
Considering the specificity of the sporting context and the influence of sleep on athletic performance, the "athlete sleep behavior questionnare" (ASBQ) was developed to evaluate sleep behavior in English-speaking athletes. The aim of this study was to perform a cross-cultural adaptation and validation of the ASBQ in Brazilian athletes. The cross-cultural adaptation was processed by procedures of translation and back-translation. Content validity was performed by 9 experts, calculating the coefficient of content validity for the equivalence of the individual items (Cvci) and the total global score (Cvct), in addition we conducted a pilot study using the translated version of the questionnaire. The next phase of the study included 52 athletes completing the translated ASBQ. The reliability of the questionnaire was assessed by the intraclass correlation coefficient (ICC), standard error of measurement (SEM) and by Cronbach's alpha (α). The ASBQ passed the process of cross-cultural adaptation, obtaining the Brazilian Version of the ASBQ (ASBQ-BR), and with acceptable values of Cvci (0.89-1.00) and Cvct (0.96). Additionally, the ASBQ-BR showed acceptable values of reliability (ICC=0.857; Cronbach's α=0.78) and a SEM of 3.05 AU. The ASBQ was translated to a newly developed ASBQ-BR, resulting in acceptable values for content validity and reliability. The ASBQ-BR provides a valuable tool for monitoring sleep behaviors in Brazilian athletes.


Characterization of T-even bacteriophage substructures. I. Tail fibers and tail tubes.
T-even bacteriophages were grown and purified in bulk quantities. The protein coats were disrupted into their component substructures by treatment with 67% dimethyl sulfoxide (DMSO). Tail fibers and tubes were purified on glycerol-CsCl-D(2)O gradients and examined with respect to sedimentation properties, subunit molecular weights, amino acid composition, isoelectric points, and morphology. It was found that intact tail fibers had a sedimentation coefficient of 12 to 13S and that dissociated fibers consisted of three classes of proteins having molecular weights of 150 K +/- 10, 42 K +/- 4, and 28 K +/- 3 daltons. A model was constructed in which the 150-K subunit folded back on itself twice to give a three-stranded rope. Each 150-K subunit then represented a half-fiber and it was proposed that the role of the 42- and 28-K subunits was to hold each half-fiber together as well as serve as a possible link with other substructures. Isoelectric point studies also indicated that there were three different proteins with pI values of 3.5, 5.7, and 8.0. Amino acid analyses indicated that fibers had a composition distinct from other phage substructures. In addition, a striking difference was noted in the content of tryptophan among the phages examined. T4B had three to five times more tryptophan than did T2L, T2H, T4D, and T6. Intact tail tubes had an S(20,w) of 31 to 38S and dissociated tubes consisted of three proteins of molecular weights 57 K +/- 5, 38 K +/- 4, and 25 K +/- 3 daltons. Based on degradation studies with DMSO, it was proposed that these three proteins were arranged in a helical array yielding the tube structure. Isoelectric point studies indicated that there were three major proteins in the tube whose pI values were 5.1, 5.7, and 8.5. No significant differences were observed in the amino acid content of tubes obtained from all the T-even bacteriophages.


Water relation, leaf gas exchange and chlorophyll a fluorescence imaging of soybean leaves infected with Colletotrichum truncatum.
Considering the potential of anthracnose to decrease soybean yield and the need to gain more information regarding its effect on soybean physiology, the present study performed an in-depth analysis of the photosynthetic performance of soybean leaflets challenged with Colletotrichum truncatum by combining chlorophyll a fluorescence images with gas-exchange measurements and photosynthetic pigment pools. There were no significant differences between non-inoculated and inoculated plants in leaf water potential, apparent hydraulic conductance, net CO2 assimilation rate, stomatal conductance to water vapor and transpiration rate. For internal CO2 concentration, significant difference between non-inoculated and inoculated plants occurred only at 36 h after inoculation. Reductions in the values of the chlorophyll a fluorescence parameters [initial fluorescence (F0), maximal fluorescence (Fm), maximal photosystem II quantum yield (Fv/Fm), quantum yield of regulated energy dissipation (Y(NPQ))] and increases in effective PS II quantum yield (Y(II)), quantum yield of non-regulated energy dissipation Y(NO) and photochemical quenching coefficient (qP) were noticed on the necrotic vein tissue in contrast to the surrounding leaf tissue. It appears that the impact of the infection by C. truncatum on the photosynthetic performance of the leaflets was minimal considering the preference of the fungus to colonize the veins.


TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain.
Activation of primary afferent nociceptors produces acute, short-lived pain, and tissue or nerve injury induces long-term enhancement of nociceptive processing, manifested as hypersensitivity to thermal and mechanical stimulation. Here we used a chemical-genetic and pharmacological approach to study the contribution of the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of injury-induced persistent pain. We performed the studies in wild-type mice and transgenic (TrkB(F616A)) mice that express mutant but fully functional TrkB receptors. By injecting a small molecule derivative of the protein kinase inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly selective inhibition of TrkB autophosphorylation in adult mice, without interfering with the activity of other protein kinases. We report that oral administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the spinal cord, had no effect in behavioral tests of acute heat, mechanical, or chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented the development of tissue- or nerve injury-induced heat and mechanical hypersensitivity. Established hypersensitivity was transiently reversed by intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged mechanical hypersensitivity produced by these chemical injuries was prevented by 1NM-PP1 inhibition of TrkB signaling. We conclude that TrkB signaling is not only an important contributor to the induction of heat and mechanical hypersensitivity produced by tissue or nerve injury but also to the persistence of the pain.


Novel Polyamides with 5H-Dibenzo[b,f]azepin-5-yl-Substituted Triphenylamine: Synthesis and Visible-NIR Electrochromic Properties.
In this study, a new diamine monomer, namely 4,4'-diamino-4″-(5H-dibenzo[b,f]azepin-5-yl)triphenylamine, was prepared and polymerized with four kinds of dicarboxylic acids via direct polycondensation reaction resulting in a novel series of soluble and electroactive polyamides (PAs). The tough thin films of all PAs could be solution-cast onto an indium-tin oxide (ITO)-coated glass substrate owing to the good solubility in polar organic solvents. Two pairs of obvious redox peaks for these films were observed in cyclic voltammetry (CV) with low onset potentials (Eonset) of 0.37⁻0.42 V accompanying with remarkable reversible color changes between light yellow and dark blue. A new absorption peak at around 915 nm emerged in near infrared (NIR) spectra; the increasing potential indicated that PAs could be used as a NIR electrochromic material. Moreover, the PAs showed high coloration efficiency (CE; η) in the range of 190⁻259 cm² C-1.


Metalation of pyridines with nBuLi-Li-aminoalkoxide mixed aggregates: The origin of chemoselectivity.
The reactivity of alkyllithium-lithium-aminoalkoxide unimetallic superbases has been investigated. These systems are used for deprotonative lithiation of pyridine derivatives in apolar non-coordinating media with excellent regio- and chemoselectivity, in deep contrast with alkyllithium. With the aim of getting a better understanding of the chemistry behind these promising reagents, we have carried out a joint experimental and theoretical study of the metalation of 2-chloropyridine with combinations of nBuLi and (S)-(-)-N-methyl-2-pyrrolidinylmethoxide (LiPM). Nucleophilic addition or alpha-lithiation has been observed, depending on conditions (solvent, temperature, stoichiometry), while ortho-metalation was not detected. Theoretical calculations using Density Functional Theory (B3LYP/6-31G(d) method) have then been carried out in gas phase at 195 K to characterize the relevant chemical species (reactive aggregates, transition structures) and estimate free energies of activation and relative reaction rates. Solvent effects in hexane have been neglected according to previous calculations. The effect of coordinating solvents such as THF has been qualitatively discussed. A major achievement of the present work has been to demonstrate that chemoselectivity crucially depends on aggregate type: dimers systematically lead to nucleophilic addition, while tetramers lead to alpha-lithiation. Besides, the calculations predict dimers to be more reactive than tetramers, yet they are much less stable, so that the observed selectivity results from the combination of both properties. A simple procedure to evaluate the basicity of an organlithium compound has been proposed. It has allowed us to show that the nBuLi-LiPM tetramer has a significantly larger basicity than its corresponding dimer, which is not at all the case for nBuLi aggregates, thus explaining differences in selectivity. Solvent and temperature effects on nBuLi-LiPM reactivity have been analyzed. By increasing the temperature in hexane, or changing the solvent from hexane to THF, dimer concentration is expected to rise, and likewise the weight of nucleophilic addition rises, in agreement with the experimental findings.


Interferon-γ moderation of poor sleep maintenance and depressed mood in community-dwelling older adults.
Depressive symptoms, such as depressed mood, are common in older adults and associated with an increased risk for morbidity and mortality. Given the evidence that sleep disturbance and alterations in interferon (IFN)-γ biology are associated with depression risk, this study examines the separate and joint contributions of poor sleep maintenance and IFN-γ to depressed mood in older adults. Community-dwelling, non-depressed older adults (n = 36, 72.1 ± 6.8 years) underwent a night of polysomnography to assess sleep maintenance [i.e. wake time after sleep onset (WASO)]. The morning after polysomnography, plasma levels of IFN-γ were evaluated along with self-reported depressed mood throughout the day. Multivariate linear regression tested associations of WASO and IFN-γ with the severity of depressed mood. In addition, moderation and mediation models examined the role of IFN-γ for the relationship between WASO and depressed mood. A greater amount of WASO (p < 0.05) and higher levels of IFN-γ (p < 0.01) were both associated with the severity of depressed mood. Moreover, IFN-γ moderated the relationship between WASO and depressed mood (p < 0.01), such that WASO was more strongly related to the depressed mood among those with higher IFN-γ, than among those with lower IFN-γ. However, IFN-γ did not mediate the relationship between WASO and depressed mood. In this study of older adults, poor sleep maintenance and higher levels of IFN-γ were both related to depressed mood. Moreover, IFN-γ moderated the relationship between poor sleep maintenance and depressed mood. Together, these findings suggest that older adults with higher IFN-γ are at heightened risk for depressive symptoms following sleep disturbance.


Exoskeleton Assistance Improves Crouch during Overground Walking with Forearm Crutches: A Case Study.
Research, development and testing of wearable robotic exoskeletons for gait training and improved mobility in children with cerebral palsy (CP) and other movement disorders has become increasingly prevalent in recent years. Broadly, these devices are split into two categories: fully wearable devices that are affixed to the lower limbs and/or pelvis and systems that include a mobile frame that moves with the user. The former systems have generally targeted more functional individuals who are independent walkers while the latter target more affected individuals who do not ambulate on their own. The best strategy for children in the middle of this mobility spectrum (GMFCS III), who can walk short distances using assistive instruments like crutches or walkers, is not clear. Yet, these children may benefit most from gait training because they are at the highest risk to lose their independent mobility. Here, we present a case study of a wearable robotic exoskeleton for overground walking in a child with CP at GMFCS III. Our results demonstrate that the exoskeleton was able to synchronize assistance to five discrete phases of the gait cycle during overground walking with forearm crutches. Peak knee extension improved on average by 10 degrees in the right leg and 7 degrees in the left leg when walking with exoskeleton assistance during early stance, mid-stance and late swing without reduction in muscle activity. Therefore, state-based control for providing robotic extension assistance to individuals with crouch from CP who walk with assistive instruments should be further investigated as a potential rehabilitation strategy.


Vitamin D Receptor (VDR) Polymorphisms in Pediatric Patients Presenting With Hodgkin's Lymphoma.
Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor types than in healthy individuals, suggesting that some polymorphisms (Cdx2, Fok1, Bsm1, Apa1, Taq1) contribute to tumor development. There is no previous report on VDR polymorphism in Hodgkin's lymphoma (HL) patients. VDR polymorphism patterns in 95 pediatric HL cases with 100 healthy controls were compared. No statistically significant difference was found between the patient group and control group in terms of Cdx2, Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P>0.5). Our findings suggest that VDR polymorphisms may not play a role in HL development.


Richter Transformation of Chronic Lymphocytic Leukemia: A Review of Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography and Molecular Diagnostics.
Chronic lymphocytic leukemia (CLL) is a low-grade B-cell proliferative disease with a generally indolent course. In a few cases, it undergoes transformation and becomes a more aggressive malignancy, such as diffuse large B-cell lymphoma (DLBCL). This process, which is called Richter transformation (RT), is often detected too late and is associated with a poor prognosis. There are multiple molecular diagnostic approaches to detect RT in preexisting CLL. Metabolic imaging using 18-fluorine fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) can be a very useful tool for early detection of RT and which can hence allow for timely intervention, thereby improving the patient's chances of survival.


3D bioprinting processes: A perspective on classification and terminology.
This article aims to provide further classification of cell-compatible bioprinting processes and examine the concept of 3D bioprinting within the general technology field of 3D printing. These technologies are categorized into four distinct process categories, namely material jetting, vat photopolymerization, material extrusion and free-form spatial printing. Discussion will be presented on the definition of classification with example of techniques grouped under the same category. The objective of this article is to establish a basic framework for standardization of process terminology in order to accelerate the implementation of bioprinting technologies in research and commercial landscape.


Lupin leghemoglobins during root nodule development.
Two yellow lupin leghemoglobins, Lb I and Lb II, were purified to homogeneity using the HPLC technique for final separation. Lb I and Lb II were identified by the N-terminal sequences and their reaction with antibodies against electrophoretically pure leghemoglobin. The third Lb species was detected by the combined method of isoelectrofocusing and PAGE of Lb I. It seems that Lb III represents a posttranslational modification of Lb I. Developmental changes in Lb multiple forms were examined using the Western blotting method. The content of leghemoglobin, first detectable approximately 3 weeks after infection, increased up to 6-7 weeks, and then it remained at the same level until 8-9 weeks after the infection. At the early stages of nodule formation Lb I prevailed over Lb II, while later Lb II became the predominant form. This suggests physiological role of particular forms and precise regulation of the expression of Lb genes.


Diamino protic ionic liquids for CO2 capture.
A series of multifunctional protic ionic liquids (PILs), some of which are based on a combination of primary and tertiary amines in the same moiety coupled with a carboxylic acid, have been synthesised and employed for CO2 capture, yielding absorption capacities comparable to standard absorbents. In contrast to traditional amine absorbers, CO2 was found to desorb at lower temperatures and hence could result in a significant reduction in both the energy required to strip the absorber of CO2 and the thermally activated degradation mechanisms, which in traditional absorbers result in the loss of absorber and the production of toxic compounds. The lower basicity of the amine sites resultant from PIL formation decreases the binding energy of the CO2 to the absorber. The weaker basicity is also evidenced by lower pH of the PIL CO2 absorbers, which reduces common corrosion problems associated with traditional amine absorbers.


Innovations for prevention and care of oral candidiasis in HIV-infected individuals: Are they available?-A workshop report.
Oral candidiasis (OC) is the most prevalent HIV-related oral lesion in patients on combined anti-retroviral therapy (cART) or without cART. Management is challenged in some patients by development of resistance to azole drugs, such as fluconazole. Recent scientific knowledge about OC pathogenesis, the role of OC in the immune reconstitution inflammatory syndrome (IRIS), the relationship of OC with the microbiome, and novelties in OC treatment was discussed in an international workshop format. Literature searches were conducted to address five questions: (a) Considering the pathogenesis of Candida spp. infection, are there any potential therapeutic targets that could be considered, mainly in HIV-infected individuals resistant to fluconazole? (b) Is oral candidiasis part of IRIS in HIV patients who receive cART? (c) Can management of the oral microbiome reduce occurrence of OC in patients with HIV infection? (d) What are the recent advances (since 2015) regarding plant-based and alternative medicines in management of OC? and (e) Is there a role for photodynamic therapy in management of OC in HIV-infected patients? A number of the key areas where further research is necessary were identified to allow a deeper insight into this oral condition that could help to understand its nature and recommend alternatives for care.


Effect of Oxygen Concentration on C-Photoassimilate Transport from Leaves of Salvia splendens L.
Partitioning and transport of recently fixed photosynthate was examined following (14)CO(2) pulse-labeling of intact, attached leaves of Salvia splendens L. maintained in an atmosphere of 300 microliters per liter CO(2) and 20, 210, or 500 milliliters per liter O(2). Under conditions of increasing O(2) (210, 500 milliliters per liter), a smaller percentage of the recently fixed (14)C in the leaf was allocated to starch, whereas a greater percentage of the fixed (14)C appeared in amino acids, particularly serine. The increase in (14)C in amino acids was reflected in material exported from source leaves. A higher percentage of (14)C in serine, glycine, and glutamate was recovered in petiole extracts when source leaves were maintained under elevated O(2) levels. Although pool sizes of these amino acids were increased in both the leaves and petioles with increasing photorespiratory activity, no significant changes in either (14)C distribution or concentration of transport sugars (i.e. stachyose, sucrose, verbascose) were observed. The data indicate that, in addition to being recycled intracellularly into Calvin cycle intermediates, amino acids produced during photorespiration may also serve as transport metabolites, allowing the mobilization of both carbon and nitrogen from the leaf under conditions of limited photosynthesis.


Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of response to therapy.
In cases of metastatic disease of the spine, monitoring the response to medical therapy with plain radiography, bone scanning, and conventional spin-echo sequence MR imaging is unsatisfactory because of the insensitivity or nonspecific findings of these imaging modalities. The purpose of this study was to investigate signal intensity changes of bone marrow after therapy by using diffusion-weighted MR imaging to monitor the response to medical therapy in cases of metastatic disease of the spine. Twenty-four patients with metastatic disease of the spine were examined with MR imaging. Diffusion-weighted MR imaging and spin-echo MR imaging were performed in all patients before and after radiation therapy. Follow-up diffusion-weighted MR imaging and spin-echo MR imaging were performed for comparison purposes in nine cases at 1 month, in seven cases at 2 months, in seven cases at 3 months, and in three cases at 6 months after therapy. The diffusion-weighted MR imaging sequences were based on a steady-state free precession with a low b value (165 s/mm(2)) and a single shot stimulated echo-acquisition mode with a high b value (650 s/mm(2)). Apparent diffusion coefficient maps were obtained using two different b values incorporated in a diffusion-weighted single shot stimulated echo-acquisition mode sequence. Apparent diffusion coefficient maps were obtained in three cases. Signal intensity changes of the metastatic disease of the vertebral bone marrow before and after therapy on conventional spin-echo sequence and diffusion-weighted MR images were evaluated. As shown by diffusion-weighted MR imaging, metastatic disease of the vertebral bone marrow included in our study before therapy was hyperintense to normal vertebral bodies. In 23 patients with clinical improvement, metastatic disease of the spine after therapy was hypointense relative to normal vertebral bodies on the follow-up diffusion-weighted MR images. In one patient with hepatocellular carcinoma, the clinical symptoms did not improve and follow-up bone scanning performed 6 months after therapy showed increased uptake. Persistent hyperintense bone marrow after therapy was also noted on diffusion-weighted MR images. Decreased signal intensity of the metastatic disease of the spine on diffusion-weighted MR images was observed >1 month after therapy. Diffusion-weighted MR imaging shows that, with successful therapy, there is decreased signal intensity of metastatic disease of the vertebral bone marrow.


Emergency surgery: half a day does make a difference.
The emergency operating patterns in a district general hospital were significantly altered by the introduction of an afternoon emergency theatre list co-ordinated by a consultant anaesthetist. Before the introduction of the list, 88% of emergency operations were carried out after 17.00, with 40% of cases waiting until after 22.00. Introduction of the emergency session significantly reduced the operations performed after 17.00 to 53%, with only 12% being delayed until after 22.00.


Disruption of quaternary structure in Escherichia coli dihydrodipicolinate synthase (DHDPS) generates a functional monomer that is no longer inhibited by lysine.
Escherichia coli dihydrodipicolinate synthase (DHDPS, E.C. 18.104.22.168), a natively homotetrameric enzyme was converted to a monomeric species through the introduction of destabilising interactions at two different subunit interfaces allowing exploration of the roles of the quaternary structure in affecting catalytic competency. The double mutant DHDPS-L197D/Y107W displays gel filtration characteristics consistent with a single non-interacting monomeric species, which was confirmed by sedimentary velocity experiments. This monomer was shown to be catalytically active, but with reduced catalytic efficiency (k(cat)=9.8±0.5s(-1)), displaying 8% of the specific activity of the wild-type enzyme. The Michaelis constants for the substrates pyruvate and for (S)-aspartate semialdehyde increased by an order of magnitude, indicating that quaternary structure plays a significant role in substrate specificity. This monomeric species exhibited an enhanced propensity for aggregation and inactivation, indicating that whilst the oligomerization is not an intrinsic criterion for catalysis, higher oligomeric forms may benefit from both increased catalytic efficiency and diminished aggregation propensity. Furthermore, allosteric inhibition by (S)-lysine was abolished for DHDPS-L197D/Y107W, confirming the importance of the dimeric unit as the minimal functional assembly for efficient (S)-lysine binding.


Spontaneous Hemarthrosis of the Knee - Late Complication of Flexible Femur Nailing: A Case Report.
We present a case report of acute spontaneous knee hemarthosis due to erosion of the nail through the knee joint capsule in a boy, seven months following retrograde flexible nailing for fractured femur. Careful positioning of the location of the insertion site of flexible nails and proper nail tip management are important to avoid this rare late complication.


Tandem mass spectrometry of platinated quadruplex DNA.
Quadruplexes are higher-order structures formed by G-rich DNA strands that are involved in various processes of cell cycle regulation, such as control of telomere length and participation in gene regulation. Because of these central biological functions, quadruplex DNA represents a promising target for cancer therapy, e.g. by applying organometallic drugs, such as cisplatin. High-resolution electrospray tandem mass spectrometry is evaluated as a technique for exploring structural features of unplatinated and platinated quadruplexes. Results of experiments on tetramolecular, bimolecular and monomolecular quadruplexes provide information about the extent of platination and the binding sites of the drug. The dissociation behavior of the different types of quadruplexes is compared. Tetramolecular quadruplexes were found to weave out a strand end in order to provide a platination site, and their fragmentation is characterized by the release of an unplatinated strand and the formation of a platinated triplex. Partial opening of the structure in combination with the loss of small fragments leads to truncated quadruplex ions. For the bimolecular quadruplexes studied, strand separation is the predominant dissociation pathway. Depending on the loop sequence, cross-linking of the loops by cisplatin is demonstrated. Distinct differences in the product ion spectra of unannealed and annealed monomolecular sequences provide proof of quadruplex formation and show that platination preferentially occurs at the terminal regions.


[Construction and identification for cell strain of anti-human seminal plasma phospholipase A2 monoclonal antibody].
To establish and evaluate the anti-human seminal plasma phospholipase A2 (PLA2) monoclonal antibody (McAb). After having been separated and purified from human seminal plasma by PEG precipitation, Sephacryl S-300 column chromatography, DEAE-Sephadex A-25 column chromatography and HA column chromatography, PLA2 was regarded as an antigen to immune BALB/C mouse to produce anti-human seminal plasma PLA2 McAb. The PLA2 McAb sensitivity and specificity were performed by ELISA technique and Western-blot analysis, respectively. The molecular weight of PLA2 depurated with 245 fold purification from human seminal plasma was about 34,900, while the sensitivity and typing of its McAb were 1:5(6)-1:5(8) and IgM (kappa) with a satisfied Western-Blot results. The PLA2, which had not been reported in international and domestic papers, may be a new type of PLA2. The establish of its McAb will provide significant tools for the research of the relationship between PLA2 in human seminal plasma and male fertility.


Distinctive activation mechanisms and functions for protein kinase Cdelta.
PKCdelta (protein kinase Cdelta) is a serine/threonine kinase that plays a key role in growth regulation and tissue remodelling. Traditional models of PKC activation have focused on lipid cofactors and anchoring proteins that localize the active conformation of PKCdelta to membranes, in close proximity with its target substrates. However, recent studies identify a distinct mode for PKCdelta activation involving tyrosine phosphorylation by Src family kinases. The tyrosine-phosphorylated form of PKCdelta (which accumulates in the soluble fraction of cells exposed to oxidant stress) displays lipid-independent kinase activity and is uniquely positioned to phosphorylate target substrates throughout the cell (not just on lipid membranes). This review summarizes (1) recent progress towards understanding structure-activity relationships for PKCdelta, with a particular focus on the stimuli that induce (and the distinct functional consequences that result from) tyrosine phosphorylation events in PKCdelta's regulatory, hinge and catalytic domains; (2) current concepts regarding the role of tyrosine phosphorylation as a mechanism to regulate PKCdelta localization and actions in mitochondrial and nuclear compartments; and (3) recent literature delineating distinct roles for PKCdelta (relative to other PKC isoforms) in transcriptional regulation, cell cycle progression and programmed cell death (including studies in PKCdelta-/- mice that implicate PKCdelta in immune function and cardiovascular remodelling). Collectively, these studies argue that the conventional model for PKCdelta activation must be broadened to allow for stimulus-specific differences in PKCdelta signalling during growth factor stimulation and oxidant stress.


Colonoscopy first for iron-deficiency anaemia: a Numbers Needed to Investigate approach.
British Society of Gastroenterology guidelines recommend that gastrointestinal investigations should be considered in males and post-menopausal women presenting with iron-deficiency anaemia (IDA). To compare the diagnostic yields and clinical effectiveness of upper and lower gastrointestinal (GI) investigation in detecting malignancy among patients presenting with IDA. Retrospective review of case notes, endoscopy records and radiology reports. We reviewed the results of 3798 investigations in 2600 patients presenting to our hospital with IDA from October 1995 to December 2003. The findings of the 2318 gastroscopies were compared with those of the 896 colonoscopies and the 584 barium enemas. Patients diagnosed with GI malignancy were identified and their outcomes determined. Gastroscopy identified 44 patients with newly-diagnosed upper GI cancer (18 oesophageal, 26 gastric). Thus for patients being gastroscoped for IDA, the Numbers Needed to Investigate (NNI) to detect each cancer was 53. Five-year survival for these 44 patients was 10%, so the NNI to identify each curable upper GI malignancy was 527. Colonoscopy or barium enema identified 111 (7.5%) patients with newly diagnosed colorectal cancer, giving a NNI of 13. Their 5-year survival was 35%, giving a NNI to identify each curable colorectal cancer patient of 38. Potentially curable gastrointestinal malignancy was diagnosed over 13 times more commonly using colonoscopy or barium enema vs. gastroscopy. For patients presenting with IDA, our findings favour investigating the lower GI tract first, or performing both gastroscopy and colonoscopy during the same endoscopy list.


Mechanism of action of aldosterone release by prostaglandin E in isolated rat adrenal glomerulosa cells.
The effect of prostaglandin E (PGE) on aldosterone release and the mechanism of action of PGE in mediating the release of aldosterone were studied using isolated rat glomerulosa cells. PGE1 stimulated aldosterone release in a dose-dependent fashion at concentrations between 10(-8) and 10(-6) M and caused approximately a two-fold increase over the basal aldosterone level at 10(-6) M. A significant and dose-dependent increase in cAMP production was also produced by PGE1 at concentrations greater than 10(-8) M. Aldosterone release induced by 10(-7) M or 10(-6) M PGE2 was significantly reduced by a competitive receptor blocking PG-antagonist, SC 19220 (10(-7) M), but not affected by (Sar1, Ileu8)-angiotensin-II (A-II), a competitive inhibitor of A-II. PGE-stimulated aldosterone release was almost completely abolished by depleting the extracellular Ca2+ by EGTA, or by verapamil, a Ca2+-channel blocker or W-7, a calmodulin inhibitor. These findings suggest that PGE stimulates aldosterone release through the membrane receptor binding and activation of adenylate cyclase and that Ca2+-calmodulin system plays an essential role in mediating the steroidogenic action of PGE in the adrenal glomerulosa cells. However, the physiological significance of PGE in the regulation of aldosterone secretion remains to be elucidated.


A Novel GC-FID Analytical Strategy Reveals Adulteration of Fuels by Vegetable Oil.
Adulteration of diesel fuel by the addition of vegetable oil is a problem that touches several countries around the world and bypasses the complexity of the specifications regarding the automotive diesel fuel distinguishing between customs, fiscal, and commercial-environmental specifications. At an international level, the adoption of the same analysis methods is important for the harmonization processes and the fluidity of the market. In this context, we assist to the diffusion of the same fraud touching several countries or continents since the limit of the same methods are common to many specifications. For several European countries, the revenue lost as a result of this adulteration consists of billions of euros per year. This enormous amount of illicit money feeds organized criminal networks with huge social and environmental damages. This work presents a GC method to quantify vegetable oils in the range of 0.2-7% (w/w) in adulterated diesel fuel, intended for use as motor fuel, with or without extraneous heavy mineral oil. Our study was realized on 100 fraudulent samples collected by the Italian fiscal police in regular oil stations and by the Italian fiscal police and customs officers as a consequence of controls on trucks transporting, in suspicious circumstances, "oil" often declared "antistick and anticorrosion oil" or "protective oil." Conclusions and Highlights: High reliability of results, external validity, ease of replication, simple instrumentation, and sample preparation make this method well suited for a new "smart" protocol for diesel fuels analysis for customs, fiscal, and antifraud purposes.


Reversible first-order transition in Pauli percolation.
Percolation plays an important role in fields and phenomena as diverse as the study of social networks, the dynamics of epidemics, the robustness of electricity grids, conduction in disordered media, and geometric properties in statistical physics. We analyze a new percolation problem in which the first-order nature of an equilibrium percolation transition can be established analytically and verified numerically. The rules for this site percolation model are physical and very simple, requiring only the introduction of a weight W(n)=n+1 for a cluster of size n. This establishes that a discontinuous percolation transition can occur with qualitatively more local interactions than in all currently considered examples of explosive percolation; and that, unlike these, it can be reversible. This greatly extends both the applicability of such percolation models in principle and their reach in practice.


Diagnostic agreement of two calcaneal ultrasound devices: the Sahara bone sonometer and the Achilles+.
Quantitative ultrasound for the assessment of skeletal status is an evolving method in the diagnosis of osteoporosis. In this cross-sectional study we investigated the diagnostic agreement between the Sahara bone sonometer and the Achilles+ with respect to broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness/quantitative ultrasound index (QUI). 309 healthy females without diseases or medications known to influence bone metabolism (with the exception of oestrogen) were recruited at two participating centers (Erlangen and Berlin). 33% of subjects were taking oestrogens. There was no significant difference in BUA, SOS, and stiffness/QUI between oestrogen and non-oestrogen takers. In vivo precision (expressed as root mean square coefficient of variation) was calculated from two repeat measurements and analyzed in both centres. Mean values were 1.57% (BUA Achilles+), 3.64% (BUA Sahara), 0.35% (SOS Achilles+), 0.39% (SOS Sahara), 2.22% (stiffness Achilles+) and 3.04% (QUI Sahara). Between the two devices we observed a strong correlation for SOS (r=0.89, p<0.01) and stiffness/QUI (r=0.83, p<0.01), and a moderate correlation for BUA (r=0.68, p<0.01). All parameters were moderately negatively associated with age (r=-0.38 to -0.48; p<0.01 for all correlations). Kappa (kappa) scores used to report diagnostic agreement were calculated for tertiles and "equivalent T-scores". The tertiles divide the cohort on both scanners into the same number of subjects above and below a given T-score. Diagnostic agreement using tertiles was poor to moderate (kappa< or =0.51). Diagnostic agreement using equivalent T-score agreement, again, was poor to moderate for BUA but fair to good for SOS and stiffness/QUI (0.59< or =kappa< or =0.73). We conclude that diagnostic agreement between the two devices is at best comparable to the agreement of a dual X-ray absorptiometry measurement using the same densitometer at two different skeletal sites. It is therefore insufficient to compare directly two measurements of an individual patient on both ultrasound devices. Standardization of quantitative ultrasound is very much needed.