The Complete Genome of a New Betabaculovirus from Clostera anastomosis.
Clostera anastomosis (Lepidoptera: Notodontidae) is a defoliating forest insect pest. Clostera anastomosis granulovirus-B (ClasGV-B) belonging to the genus Betabaculovirus of family Baculoviridae has been used for biological control of the pest. Here we reported the full genome sequence of ClasGV-B and compared it to other previously sequenced baculoviruses. The circular double-stranded DNA genome is 107,439 bp in length, with a G+C content of 37.8% and contains 123 open reading frames (ORFs) representing 93% of the genome. ClasGV-B contains 37 baculovirus core genes, 25 lepidopteran baculovirus specific genes, 19 betabaculovirus specific genes, 39 other genes with homologues to baculoviruses and 3 ORFs unique to ClasGV-B. Hrs appear to be absent from the ClasGV-B genome, however, two non-hr repeats were found. Phylogenetic tree based on 37 core genes from 73 baculovirus genomes placed ClasGV-B in the clade b of betabaculoviruses and was most closely related to Erinnyis ello GV (ErelGV). The gene arrangement of ClasGV-B also shared the strongest collinearity with ErelGV but differed from Clostera anachoreta GV (ClanGV), Clostera anastomosis GV-A (ClasGV-A, previously also called CaLGV) and Epinotia aporema GV (EpapGV) with a 20 kb inversion. ClasGV-B genome contains three copies of polyhedron envelope protein gene (pep) and phylogenetic tree divides the PEPs of betabaculoviruses into three major clades: PEP-1, PEP-2 and PEP/P10. ClasGV-B also contains three homologues of P10 which all harbor an N-terminal coiled-coil domain and a C-terminal basic sequence. ClasGV-B encodes three fibroblast growth factor (FGF) homologues which are conserved in all sequenced betabaculoviruses. Phylogenetic analysis placed these three FGFs into different groups and suggested that the FGFs were evolved at the early stage of the betabaculovirus expansion. ClasGV-B is different from previously reported ClasGV-A and ClanGV isolated from Notodontidae in sequence and gene arrangement, indicating the virus is a new notodontid betabaculovirus.


Persistent glucose production and greater peripheral sensitivity to insulin in the neonate vs. the adult.
Insulin resistance has been reported to partially explain the clinical appearance of neonatal hyperglycemia. To determine the relative resistance to insulin of glucose production vs. glucose utilization, the euglycemic hyperinsulinemic clamp technique was employed for the first time in the human neonate and was combined with stable isotopic determination of glucose production and glucose utilization. The basal rates of glucose production and glucose utilization were determined, after which each neonate was clamped at his or her own euglycemic glucose concentration while receiving regular human insulin at one rate of 0.2, 0.5, 1.0, 2.0, or 4.0 mU. kg-1.min-1. Persistent glucose production (> or = 1 mg.kg-1.min-1) during the clamp was recorded for all groups. A significant increase in the glucose infusion rate (P < 0.001) and in percent glucose utilization (P < 0.01) occurred in the 2.0 and 4.0 mU.kg-1.min-1 insulin groups. Metabolic clearance rate of insulin was significantly greater in the neonate compared with the adult at the 2.0 mU.kg-1.min-1 insulin infusion rate (P = 0.036). Our results indicate that, in contrast to the adult, the neonate has persistent glucose production (P = 0.001) and greater peripheral sensitivity to insulin (P = 0.015).


Changes in abundance of Lactobacillus spp. and Streptococcus suis in the stomach, jejunum and ileum of piglets after weaning.
This present study investigated the changes in bacterial community composition, with an emphasis on Lactobacillus spp. and Streptococcus suis populations as potentially beneficial and harmful groups, in the stomach, jejunum and ileum of piglets after weaning (21 days postpartum) by 16S rRNA gene-based methods. Denaturing gradient gel electrophoresis analysis showed that, after weaning, predominant bands related to Lactobacillus spp. disappeared and were replaced by potential pathogenic species, such as Peptostreptococcus anaerobius, Moraxella cuniculi, S. suis and Porphyromonas catoniae. Real-time PCR revealed that the abundances of lactobacilli and Lactobacillus sobrius as a proportion of total bacterial abundance were significantly lower in the stomach, jejunum and ileum of weaned piglets than in 21-day-old piglets. A specific and sensitive real-time PCR assay was developed for quantification of the important pathogen S. suis within gastrointestinal microbiota. The assay showed that S. suis predominated in the stomach samples of weaned piglets with population levels up to 10(7) copies g(-1) digesta, while it was not detected in the stomach before weaning. Streptococcus suis was not dominant in the jejunum and ileum digesta before weaning, but became dominant after weaning, with population levels up to 10(7) copies g(-1) digesta. The results demonstrated for the first time the postweaning dominance of the potentially harmful S. suis in piglet intestine. The results also suggest that the defensive barrier of the stomach can be impaired as S. suis became dominant while the proportion of Lactobacillus populations decreased after weaning, which may further result in an increase of S. suis abundance in the intestine.


Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice.
Chemokine receptors transduce signals important for the function and trafficking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevance is unclear. To address the biological role of CCR8, we generated CCR8 deficient (-/-) mice. Here we report defective T helper type 2 (Th2) immune responses in vivo in CCR8(-/)- mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine production that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 cells developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.


Effect of L-aspartate on the ventilatory response to hypoxia in sedated newborn piglets.
L-aspartate (L-ASP) acts as an excitatory amino acid neurotransmitter at the synapses of brain stem respiratory neurons. In order to determine the effect of L-ASP on the neonatal ventilatory response to hypoxia, 9 control piglets [age 4.3 +/- (SD) 0.9 days, weight 1.9 +/- 0.5 kg] and 9 L-ASP-treated animals [age 5.0 +/- (SD) 1.4 days, weight 2.1 +/- 0.7 kg] were studied. Minute ventilation, oxygen consumption, arterial blood pressure, and blood gases were measured in sedated piglets while spontaneously breathing room air and during 1, 5, and 10 min of hypoxia (O2 concentration in inspired gas 0.10). Measurements were obtained before and 60 min after the administration of L-ASP (580 mg/kg i.v. over 1 h) or 5% dextrose solution. In the control animals, the ventilatory response to hypoxia was similar before and after dextrose infusion. In contrast, a significant and sustained increase in ventilation was observed at 1, 5, and 10 min of hypoxia after the administration of L-ASP. Changes in oxygen consumption, heart rate, arterial blood pressure, pH, and arterial O2 tension with hypoxia were similar before and after the L-ASP infusion, while the arterial CO2 tension decreased significantly during hypoxia after the administration of L-ASP. These data suggest that the excitatory amino acid L-ASP is an important mediator of the hypoxic hyperventilation in the neonate. We speculate that the administration of exogenous L-ASP modifies the balance of central nervous system neurotransmitters during hypoxia, resulting in predominance of excitatory neurotransmission.


Efficacy of immunization against hepatitis B virus infection in children with cancer.
The purpose of this study was to evaluate the impact of hepatitis B prophylaxis in preventing hepatitis B infection in children with malignancy. Between May, 1993, and September, 1998, a total of 151 children (95 boys, 56 girls), 29 (19%) with lymphoma, 58 (39%) with leukemia, and 64 (42%) with solid tumor, were screened for hepatitis B virus (HBV). The mean age was 7. 5 +/- 2.5 years. Children with negative serology received active and/or passive immunization. HBsAg and anti-HBs were positive prior to vaccination in 16 (10%) and 17 (11%) children, respectively. One hundred eighteen children (78%) of one hundred fifty-one with negative serology were included in the vaccination program. The vaccine dose was 40 microg. Children with solid tumor and lymphoma received recombinant hepatitis B vaccine at diagnosis, repeated at months 1, 2, and 12. Hyperimmunglobulin was administered monthly in children with leukemia during the intensive chemotherapy period. They were then vaccinated following the third month of maintenance therapy with the schedule described above. Anti-HBs titers were measured every 3 months, and titers above 10 mlU/ml were accepted as protective. Anti-HBs positivity after the first three doses was 77% in solid tumors, 88% in acute leukemia, and 48% in lymphomas. Anti-HBs positivity with respect to diagnosis in children completing the vaccination schedule was 94% in solid tumor, 90% in leukemia, and 74% in lymphoma (P > 0.05). Thirty-three percent of children have not received the fourth dose as yet. In total 78% of the children developed protective antibody titers with or without the fourth dose, and none was infected with HBV during 3 years of follow-up. Ten (39%) of twenty-six children who remained unresponsive to immunization were infected with HBV. These data reveal that HBV prophylaxis is necessary and that our vaccination schedule is effective in preventing HBV infection in these children.


The comparison of severity and prevalence of major depressive disorder, general anxiety disorder and eating disorders before and after bariatric surgery.
Severe obesity is highly co-morbid with psychiatric disorders and may have effect on the quality of life. This study aimed to compare severity and prevalence rate of depression, anxiety and eating disorders and quality of life in severe obese patients before and 6 months after the gastric bypass surgery. This was a prospective observational study which conducted at Hazarat Rasool-Akram Hospital in Tehran, 2012. Questionnaires included demographic questions, eating disorder Inventory (EDI), The Short Form Health Survey (SF-36) for quality of life, Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) and Hamilton Rating Scale for Depression (HRSD) and anxiety (HRSA). Participants were interviewed two times, before surgery and six months after, to determine changes of the disorders. Patients with the history of bariatric surgery, individuals younger than 18 year old and those who disagreed to join the study were excluded. In assessing the eating disorder inventory-3rd version (EDI-3), Significant reduction in drive for thinness (DT) (p= 0.010), bulimia (B) (p< 0.0001) and body dissatisfaction mean (BD) (0.038) was observed at the 6-month follow-up. At this period, the mean for physical component summary of SF36, significantly decreased (p< 0.0001), however mental component summary did not significantly differ (p= 0.368); Also differences in severity of anxiety (p= 0.852), and depression in HRSD (p= 0.311), prevalence of depression (p= 0.189) and prevalence of general anxiety disorder according to SCID (p=0.167) did not differ significantly, at this period. Although weight loss after bariatric surgery improved the physical component of quality of life, this improvement did not affect the mental aspect of life, depression and anxiety and it seems that these psychopathologies need attention and treatment in addition to weight loss treatments in patients with obesity.


Role of the crown in tree resistance against high winds.
Rather than using wooden sticks to simulate the breakage of trees in high winds as in most research, we employ fresh samples from camphor and Formosa gum with branches and leaves to certify the crucial role of the tree crown. By using a blowdown wind tunnel with a maximum wind speed of 50 m/s, we purposely reduce the number of leaves and show that the drag force will drop by as much as two thirds when half pruned. Based on real observations, we model the leaf by an open and full cone in the presence of light and strong winds, and calculate how their corresponding cross-sectional area A and drag force F vary with wind speed v. Different slopes before and after the formation of a full cone are predicted and confirmed when these two quantities are plotted in full-log scale. Compared to the empirical value, our simple model gave α=2/5 and 2/3 for A∝v^{-α} and β=4/5 and 2/3 for F∝v^{β} at low and high winds. Discrepancies can be accounted for by including further details, such as the reorientation of open cones and the movement of branches.


The effect of open and closed endotracheal tube suctioning system on respiratory parameters of infants undergoing mechanical ventilation.
Mechanical ventilation is used for some infants in neonatal intensive care units (NICU) due to many physiological and clinical causes. Since these patients have endotracheal tubes, cleaning and keeping the airways open through suctioning should be done to increase oxygenation. This study aimed to evaluate effect of open and closed suctioning methods on respiratory parameters of infants undergoing mechanical ventilation. In this crossover clinical trial, 44 infants were selected among those undergone mechanical ventilation in NICU of Isfahan's Al-Zahra Hospital using convenience sampling method. The subjects were randomly divided into two groups. In the first group, open suctioning was carried out and after three hours of cleaning, closed suctioning was done. In the second group, closed suctioning was firstly done and following three hours of cleaning, open suctioning was implemented. Respiratory rate (RR) and percentage of arterial blood oxygen saturation was measured before, during and after each type of suctioning. Data were analyzed using repeated measures ANOVA and independent student's t-test. There was a significant difference between mean respiratory rate and arterial blood oxygen saturation in infants before, during and after the closed and open suctioning. The percentage of arterial blood oxygen saturation had a significant reduction in open method compared to closed method during suctioning and immediately after it. RR three minutes after suctioning showed a significant reduction in both steps in open method compared to closed method. Close method caused fewer changes in hemodynamic status of infants. Therefore, in order to prevent respiratory complications in infants, nurses are recommended to perform the endotracheal tube suctioning by closed method.


Pediatric Obesity and Perceived Exertion: Difference Between Weight-Bearing and Non-Weight-Bearing Exercises Performed at Different Intensities.
Excess body weight composes an important limitation to exercise in obese youth. The aim of this study was to compare the perceived exertion of obese adolescents between weight-bearing (WB; running) and non-weight-Bearing (NWB; cycling) exercises performed at moderate (55% VO2max) and high (75% VO2max) intensities. Twenty-four obese adolescents were recruited. After assessment of their body composition and physical capacities, they had to complete four isoenergetic exercise sessions: (1) a cycling session performed at 55% of their maximal capacities (NWB-55%); (2) a cycling session set at 75% (NWB-75%); (3) a running session at 55% (WB-55%); and (4) a running session at 75% (WB-75%). Perceived exertion was assessed using a visual scale at regular interval. While no significant difference between WB and NWB modalities was observed, the adolescents expressed a significantly lower rate of perceived exertion (RPE) during exercises at 55%VO2max (P < 0.0001). An intensity × modality interaction revealed that RPE was lower at 75% VO2max during NWB exercises (P < 0.05). While obese adolescents expressed lower RPE during exercise at moderate intensity whatever its modality, low level of perceived exertion has been observed during high-intensity exercises and especially during NWB. High-intensity exercise appears well tolerated in adolescents when their body weight is supported.


[Consensus of experts on the oral health management and medical risk prevention for the patients with chronic airway diseases (2022 edition)].
Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.


Best practices for MRI systematic reviews and meta-analyses.
As defined by the Cochrane Collaboration, a systematic review is a review of evidence with a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant primary research, and to extract and analyze data from the studies that are included in the review. Meta-analysis is a statistical method to combine the results from primary studies that accounts for sample size and variability to provide a summary measure of the studied outcome. Systematic reviews of diagnostic test accuracy present unique methodological and reporting challenges not present in systematic reviews of interventions. This review provides guidance and further resources highlighting current best practices in methodology and reporting of systematic reviews of diagnostic test accuracy, with a specific focus on challenges and opportunities for MRI imaging. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.


Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment With Standard-of-Care.
Glioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) (N = 184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established (N = 40 with SOC, N = 19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM (N = 144 with SOC, N = 111 without SOC). When stratified by sex, the survival benefit of cystic GBM was only preserved in male patients (N = 303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.


Manchester Triage System version II and resource utilisation in the emergency department.
Emergency department (ED) triage systems aim to direct the best clinical assistance to those who are in the greatest urgency and guarantee that resources are efficiently applied. The study's purpose was to determine whether the Manchester Triage System (MTS) second version is a useful instrument for determining the risk of hospital admission, intrahospital death and resource utilisation in ED and to compare it with the MTS first version. This was a prospective study of patients that attended the ED at a large hospital. It comprised a total of 25,218 cases that were triaged between 11 July and 13 October 2011. The MTS codes were grouped into two clusters: red and orange into a 'high acuity/priority' (HP) cluster, and yellow, green and blue into a 'low acuity/priority' cluster. The risk of hospital admission in the HP cluster was 4.86 times that of the LP cluster for both admission route and ages. The percentage of patient hospital admission between medical and surgical specialties, in high and low priority clusters, was similar. We found the risk of death in the HP cluster to be 5.58 times that of the risk of the low acuity/priority cluster. The MTS had an inconsistent association relative to the utilisation of x-ray, while it seemed to portray a consistent association between ECG and laboratory utilisation and MTS cluster. There were no differences between medical and surgical specialities risk of admission. This suggests that improvements were made in the second version of MTS, particularly in the discriminators of patients triaged to surgical specialties, because this was not true for the first version of MTS.


Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.
Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline. The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses. Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.


The evolution of the endonasal approach for craniopharyngiomas.
Craniopharyngiomas have always been an extremely challenging type of tumor to treat. The transsphenoidal route has been used for resection of these lesions since its introduction. The authors present a historical review of the literature from the introduction of the endonasal route for resection of craniopharyngiomas until the present. Abandoned early due to technological limitations, this approach has been expanded both in its application and in its anatomical boundaries with subsequent progressive improvements in outcomes. This expansion has coincided with advances in visualization devices, imaging guidance techniques, and anatomical understanding. The progression from the use of headlights, to microscopy, to endoscopy and fluoroscopy, and finally to modern intraoperative magnetic resonance-guided techniques, combined with collaboration between otolaryngologists and neurosurgeons, has provided the framework for the development of current techniques for the resection of sellar and suprasellar craniopharyngiomas.


T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila.
T lymphocytes have been implicated in controlling the recruitment of eosinophils into the lung in murine models of allergic asthma. The mechanism by which T cells assist in the recruitment of eosinophils to the lung in these models is not completely understood. We hypothesized that eosinophil-active chemokines might be regulated by antigen (Ag)-induced T cell activation in vivo and thereby mediate T cell-dependent eosinophil recruitment. To test this hypothesis, we examined the effect of an anti-CD3 mAb on Ag-induced pulmonary eosinophilia and correlated this with the expression of three eosinophil-active chemokines: eotaxin, macrophage inflammatory protein (MIP)-1 alpha, and RANTES. We found that Ag-induced pulmonary eosinophilia was associated with the induction of eotaxin and MIP-1 alpha, but not RANTES mRNA. Prechallenge treatment with anti-CD3 mAb inhibited eotaxin, but not MIP-1 alpha and RANTES mRNA induction, and significantly reduced eosinophil accumulation in the lung. In addition, Ag-specific antibody responses and mast cell degranulation after Ag challenge in sensitized mice were not affected by T cell elimination, and were not sufficient to induce the expression of eotaxin and cause pulmonary eosinophilia. These findings suggest that eotaxin is one of the molecular links between Ag-specific T cell activation and the recruitment of eosinophils into the airways.


Talk and die revisited: bifrontal contusions and late deterioration.
Severe bifrontal contusions in an awake traumatic brain injury (TBI) patient is a challenging clinical picture, as they are prone to late deterioration. We evaluated our series of patients with severe bifrontal contusions, characterizing their clinical course and suggestions for management. We examined a prospectively collected database of TBIs for patients with severe bifrontal contusions, defined as >30 cm. Only patients with Glasgow Coma Scale score of 10 or greater were included. Patients were divided into two groups: deterioration and nondeterioration. Clinical variables were compared between the two groups. Thirteen patients met the above criteria. The mean Glasgow Coma Scale score was 13, and all were low mechanism injuries. All patients were managed with intensive care unit observation and hyperosmolar therapy to maintain serum osmolarity >300. Overall, 7 of 13 (54%) suffered an acute clinical deterioration a mean of 4.5 days postinjury. Of those managed with immediate surgical decompression, all had good outcomes and returned to work. There was no difference in contusion or edema volumes between the two groups. Awake patients with bifrontal contusions represent a unique cohort of TBI patients who are prone to rapid deterioration late in their clinical course. They have extensive frontal edema and mass effect, yet we were unable to find a correlation between edema volumes and incidence of deterioration. Based on this series and our experience in other TBI patients, we no longer utilize prophylactic infusions of hypertonic saline in the setting of TBI. We recommend managing these patients with intensive care unit admission and early intracranial pressure monitoring. If they do deteriorate despite these measures, rapid bifrontal decompression can lead to good functional outcomes.


Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Fetal Medicine Specialists and Neonatologists.
Background In cases of life-threatening maternal conditions in the periviable period, professionals may consider immediate delivery with fetal demise as a consequence of the treatment. We sought the opinion of involved medical professionals on management, reporting, and auditing in these cases. Methods We performed an online survey amongst all registered maternal-fetal medicine (MFM) specialists and neonatologists in the Netherlands. The survey presented two hypothetical cases of severe early-onset pre-eclampsia at periviable gestational ages. Management consisted of immediate termination or expectant management directed towards newborn survival. Findings In the case managed by immediate termination, 62% percent answered that fetal demise resulting from induction of labor for maternal indications should be audited only within the medical profession. In the case of expectant management, 17% of the participants agreed with this management. Some answers revealed a significant difference in opinion between the medical specialists. Conclusion Perspective of MFM specialists and neonatologists differs with regard to counseling prospect parents in case of severe early onset pre-eclampsia. The majority of professionals is willing to report late termination (after 24 weeks' gestation) for severe maternal disease to medical experts for internal audits but not for legal auditing.


Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A.
The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50-56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients.


Fracture resistance of complex amalgam restorations.
This study evaluated fracture resistance provided to complex amalgam restorations by adhesive and mechanical resistance features. The occlusal surfaces of 30 extracted molar teeth of similar size were ground flat to approximately 2 mm coronal to the CEJ. The teeth were divided into three groups. Roots were notched and embedded in acrylic resin. In two groups, four TMS Minim stainless steel pins were placed into dentin at the line angles. A copper band matrix was applied to each specimen and reinforced with compound. After applying either Copalite or Amalgambond Plus, Tytin amalgam was condensed into the matrix. The bands and excess amalgam were removed 10 minutes later, and each amalgam occlusal surface was ground flat to give the amalgam restoration a 4 mm occlusal height. Specimens were thermocycled for 2500 cycles at 6-60 degrees C with a 30-second dwell time. They were then stored in deionized water for 1 month at room temperature. A 1 mm 45 degrees bevel was placed on the facio-occlusal angle of the amalgam. Each specimen was loaded to failure in compression at 45 degrees in an Instron Testing Machine at a crosshead speed of 5 mm/min. The groups were: Group 1, four Minim pins and Copalite; Group 2, four Minim pins and Amalgambond Plus; and Group 3, Amalgambond Plus only. The data were analyzed using a one-factor ANOVA and a Tukey B post hoc test. There was no significant difference between Groups 1 and 3. The Amalgambond Plus combined with pins provided significantly greater resistance to fracture than pins or Amalgambond Plus alone (P < 0.05).


CCK is involved in both peripheral and central mechanisms controlling food intake in chickens.
The aim of this work was to study the involvement of cholecystokinin (CCK) in the control of food intake in chickens. The following aspects were studied: 1) the effects of intravenous and intracerebroventricular sulfated octapeptide of CCK (CCK-8s) on voluntary food intake; 2) the effects of two CCK-receptor antagonists. L-365,260 and L-364,718, on food intake; and 3) the ability of such drugs to block the effects of CCK-8s on food intake in the chicken. Intravenous and intracerebroventricular CCK-8s caused a decrease in food intake. Intraperitoneal L-365,260, a CCK-receptor antagonist with low affinity for the two CCK receptors described in the chicken, increases food intake. Intracerebroventricular L-364,718, a drug that has high affinity for the chicken central CCK-receptor type, increased food intake. The effect of intravenous CCK-8s on food intake was not blocked by L-364,718 or L-365,260, whereas that of intracerebroventricular CCK-8s was blocked by intracerebroventricular L-364,718. It is concluded that central endogenous CCK plays a role in the control of food intake, which is dependent on central CCK-receptor type; nevertheless, peripheral CCK also decreases food intake acting on the peripheral CCK-receptor type. The fact that intracerebroventricular L-364,718 is able to increase food intake is related to its high affinity for the central CCK-receptor type of this species. Finally, three different speculations that might explain the fact that intraperitoneal L-365,260 increases food intake are discussed.


Role of vasopressin in diabetes mellitus-induced changes in medullary transport proteins involved in urine concentration in Brattleboro rats.
In rats with streptozotocin-induced diabetes mellitus for 10-20 days, we showed that the abundance of the major medullary transport proteins involved in the urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2), and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing osmotic diuresis. To test whether vasopressin is necessary for these diabetes mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4 microg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin increased AQP2 protein abundance but decreased UT-A1 abundance compared with untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated Brattleboro rats were made diabetic for 10 days by injecting them with streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third, vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for 10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT-A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in the other groups of Brattleboro rats. We conclude that 1) administering vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1 protein abundance and 2) vasopressin is necessary for the increase in UT-A1 protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2 proteins.


First Detailed Genetic Characterization of the Structural Organization of Type III Arginine Catabolic Mobile Elements Harbored by Staphylococcus epidermidis by Using Whole-Genome Sequencing.
The type III arginine catabolic mobile element (ACME) was detected in three Staphylococcus epidermidis oral isolates recovered from separate patients (one healthy, one healthy with dental implants, and one with periodontal disease) based on ACME-arc-operon- and ACME-opp3-operon-directed PCR. These isolates were subjected to whole-genome sequencing to characterize the precise structural organization of ACME III for the first time, which also revealed that all three isolates were the same sequence type, ST329.


Familial clustering of hypereosinophilic diseases treated with mepolizumab: a case report from Japan.
We describe a female diagnosed with non-allergic asthma. On March 24, 2016, examination of the skin-biopsy specimen revealed dense eosinophilic infiltration, and the Fip-1-like 1-platelet-derived growth factor receptor a fusion gene in peripheral blood mononuclear cells was negative. She was diagnosed with idiopathic hypereosinophilic syndrome. She was treated with intravenous methylprednisolone (MPSL), and subsequent oral MPSL. Then, she started to receive a monthly mepolizumab in June 2016, and successfully withdrew from daily use of oral MPSL. The patient has a mother diagnosed with non-allergic asthma. In February 2005, she was diagnosed with eosinophilic granulomatosis with polyangitis because of elevated antineutrophil myeloperoxidase antibodies, and the skin-biopsy specimen findings. She started to receive a monthly mepolizumab in June 2016. Corticosteroid therapy was successfully withdrawn. To our knowledge, this is the first case report suggesting mepolizumab may be a useful treatment for familial clustering of hypereosinophilic diseases.


23-valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal diseases (IPDs) in the elderly: is it really effective?
Incidence of invasive pneumococcal diseases (IPDs) in Italy is constantly increasing and that is particularly true among the elderly. 23-valent polysaccharide pneumococcal vaccine (PPV23) is recommended to this age group and offered in all Italian regions. However, efficacy of PPV23 on preventing IPDs is debated. We therefore performed a review of the most recent available meta-analyses in order to assess the efficacy of PPVs. The literature search was conducted using PubMed and Scopus search engines. We used the following keywords: "pneumococcal", "polysaccharide", "vaccine", "efficacy", "elderly", "meta analysis". Only meta-analyses published in the last 7 years were selected. We examined the results of the selected meta-analyses and assessed their quality according to the PRISMA recommendations. The search returned 16 results in PubMed and 12 in Scopus: among them we selected 3 meta-analyses. According to our quality assessment, all meta-analyses showed generally positive results and almost all items of the PRISMA checklist were respected. However, the research protocol and the registration number were absent in all the 3 revisions and the flow-chart was not shown in Moberley's and Melegaro's works. In the study by Huss et al. the relative risk of developing IPDs among vaccinated subjects was 0.90 (95%CI: 0.46-1.77, I2 4.9%), indicating a very slight benefit after vaccination. This contrasts with the results of the Cochrane Review by Moberley et al., in which the PPVs showed a protective efficacy in reducing the risk of IPDs of 74% (OR 0.26, 95% CI: 0.15-0.46) with no statistical heterogeneity (I2 0%). Melegaro et al. found a reduction not statistically significant of the incidence of IPD of 65% (OR 0.35; 95% CI 0.08-1.49) among healthy elderly, while the global estimate of vaccine efficacy among high risk elderly was minimal (OR 0.80; 95% CI 0.22-2.88). Most of the studies suggest that the PPVs confer low protection against IPDs. Anyhow, their methodological heterogeneity does not allow definitive conclusions. While waiting to see the results of new trials about the efficacy of PPVs, in particular of PPV23, and the extension of the use of conjugate vaccine among the population over 65, stakeholders should be aware of the results of the meta-analyses discussed in this paper during the implementation of the vaccination programs for the elderly in Public Health.


Context sensitivity in action decreases along the autism spectrum: a predictive processing perspective.
Recent predictive processing accounts of perception and action point towards a key challenge for the nervous system in dynamically optimizing the balance between incoming sensory information and existing expectations regarding the state of the environment. Here, we report differences in the influence of the preceding sensory context on motor function, varying with respect to both clinical and subclinical features of autism spectrum disorder (ASD). Reach-to-grasp movements were recorded subsequent to an inactive period in which illusory ownership of a prosthetic limb was induced. We analysed the sub-components of reach trajectories derived using a minimum-jerk fitting procedure. Non-clinical adults low in autistic features showed disrupted movement execution following the illusion compared to a control condition. By contrast, individuals higher in autistic features (both those with ASD and non-clinical individuals high in autistic traits) showed reduced sensitivity to the presence of the illusion in their reaching movements while still exhibiting the typical perceptual effects of the illusion. Clinical individuals were distinct from non-clinical individuals scoring high in autistic features, however, in the early stages of movement. These results suggest that the influence of high-level representations of the environment differs between individuals, contributing to clinical and subclinical differences in motor performance that manifest in a contextual manner. As high-level representations of context help to explain fluctuations in sensory input over relatively longer time scales, more circumscribed sensitivity to prior or contextual information in autistic sensory processing could contribute more generally to reduced social comprehension, sensory impairments and a stronger desire for predictability and routine.


Physical Fitness Characteristics That Relate to Work Sample Test Battery Performance in Law Enforcement Recruits.
This study determined relationships between an agency-specific fitness test battery (PT500), and a work sample test battery (WSTB) in law enforcement recruits. Retrospective analysis on 219 males and 34 females from one agency was conducted. The PT500 comprised: push-ups, sit-ups, and mountain climbers in 120 s; pull-ups; and 201 m and 2.4 km runs. The WSTB comprised: 99 yard (90.53 m) obstacle course (99OC); body drag (BD) with a 165 pound (75 kg) dummy; 6 foot (1.83 m) chain link fence (CLF) and solid wall (SW) climb; and 500 yard (457.2 m) run (500R). Partial correlations, controlling for sex, calculated PT500 and WSTB relationships (p < 0.05). Stepwise regression determined whether fitness predicted WSTB performance. The 500R related to all PT500 assessments (r range = -0.127⁻0.574), 99OC related to all bar push-ups and mountain climbers, and BD related to none. The CLF related to sit-ups, pull-ups, and 2.4 km run; SW related to mountain climbers, pull-ups, and 2.4 km run (r range = -0.127⁻-0.315). Push-ups, pull-ups, and 2.4 km run were involved in predictive relationships for 99OC, CLF, SW, and 500R (r² range = 0.217⁻0.500). To perform better in the WSTB and job-specific tasks, developing upper-body strength and aerobic fitness may be beneficial.


Non-urgent care in the hospital medical emergency department in France: how much and which health needs does it reflect?
The goal was to describe the use of the medical emergency department as a source of non-urgent medical care in order to assess unmet health care needs among its users. The specific objectives were thus to assess the proportion of emergency department visits for non-urgent medical care and to describe those who used the department for this reason. A cross sectional study was performed at the emergency department in two hospitals (around 12,000 visits per year each). Subjects were interviewed before and after the visit using a standardised questionnaire. The medical emergency department of two university hospitals, one in Paris and one in Besançon (France). Each patient aged 15 and more attending the emergency department for a visit during 40 randomly selected periods of 12 hours was included. A definition of urgent care was adopted before the beginning of the study. Four expert judgments were then used for each case to determine whether the reason for the visit was urgent or not. Altogether 594 patients in the Paris emergency department and 614 in the Besançon one were included. In Besançon, the patients were older, a general practitioner was more often cited as the regular source of care, and the percentage of subsequent hospital admission was higher than in Paris (71% versus 34%). The non-urgent visits were estimated to account for 35% and 29% of the visits in Paris and Besançon respectively. Patients using the emergency department for a non-urgent visit were younger than other patients. More of them were unemployed, homeless, born outside of France, and without health insurance. Non-urgent use of the emergency department was observed in about one third of the visits. Groups using the department for primary care and/or non-urgent care were mostly young and socially fragile, with no regular source of health care. Their poor health condition suggests that there is a need for a structure providing primary care both inside and outside 'normal' working hours.


Hyperglycemia and Cancer: An Algorithm to Guide Oncology Nurses .
A dual diagnosis of cancer and hyperglycemia has demonstrated untoward effects on patients' cancer treatment, prognosis, and survival. . The purpose of this evidence-based project is to improve knowledge and awareness of the consequences of hyperglycemia in patients with cancer, increasing nurses' capability to effectively intervene. In addition, a clinical algorithm based on current evidence was developed and is presented. . An educational program was developed and pilot tested. The program addressed the etiology of hyperglycemia and its effects on patients with cancer. Knowledge of hyperglycemia in patients with cancer was assessed with a pre- and post-test. . All participants found the educational program effective and deemed the clinical algorithm useful. Results improved significantly after participation in the educational intervention.


[Orthotopic replacement of the bladder in the female].
Orthotopic substitution of the bladder in females is a procedure which is increasing worldwide. Patients with tumours of the bladder neck or the trigon, or with multifocal tumours, expanded carcinomas in situ or massive pelvic adenopathies are not eligible for the procedure. The main consideration should be the risk of urinary incontinence or hypercontinence. Our experience relates to 8 patients, the neobladder being constructed using the Studer technique. Six months postoperatively daytime continence was 100% and night-time continence 75%.


Birth Preparedness and Complication Readiness Practices Among Pregnant Adolescents in Bangkok, Thailand.
Reducing the maternal mortality ratio is one of the United Nations Sustainable Development Goals. These maternal deaths are preventable with appropriate management and care. Birth preparedness and complication readiness (BPCR) is a strategy to make prompt decisions to seek care from skilled birth attendants, resulting in reduced maternal and neonatal mortality. Despite high global rates of adolescent pregnancy, there has not yet been a study of BPCR status and associated factors among pregnant adolescents. To assess the proportion of, and associated factors for, good BPCR in adolescent pregnant women attending antenatal clinic in an urban tertiary care hospital. This cross-sectional survey was conducted among adolescent pregnant women attending antenatal clinic at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Thailand, from September 1st, 2018 to March 31st, 2019. A total of 134 adolescent pregnant women were recruited. The participants and their parents or legal guardians were informed of the study process at the antenatal clinic before their parents or legal guardians, granted written consent on their behalf. The participants were interviewed using the BPCR index, which was adapted from the John Hopkins Program for International Education in Gynecology and Obstetrics. The proportion of good BPCR in adolescent pregnant women in an urban tertiary care hospital was 78.4%. The most mentioned aspect of BPCR was planning to give birth with a skilled provider (92.5%). The significant associated factor for good BPCR was the number of ANC ≥ 4 (odds ratio 3.2, 95% CI 1.13-9.05, p=0.023). This study demonstrated that the proportion of good BPCR among adolescent pregnant women attending an urban tertiary care hospital was high. The associated factor of good BPCR was the number of ANC ≥ 4.


Cooperativity, absolute interaction, and algebraic optimization.
We consider a measure of cooperativity based on the minimal interaction required to generate an observed titration behavior. We describe the corresponding algebraic optimization problem and show how it can be solved using the nonlinear algebra tool SCIP. Moreover, we compute the minimal interactions and minimal molecules for several binding polynomials that describe the oxygen binding of various hemoglobins under different conditions. We compare their minimal interaction with the maximal slope of the Hill plot, and discuss similarities and discrepancies with a view towards the shapes of the binding curves.


Effect of nicotinic acid conjugated to DNA-transfecting complexes targeted at the transferrin receptor of HeLa cells.
A conjugate consisting of streptavidin (biotinylated transferrin)-biotinylated polylysine for DNA delivery to cells was modified by partial nicotinylation of the polylysine component of the conjugate and used for transfection studies. A conjugate of biotin10-nicotinyl60-polylysine250 containing 60 weakly basic nicotinyl (pyridine-3-carboxyl) residues was prepared. The design of the modified polylysine was directed to the possible binding of H+ ions in the endosome-lysosomal vesicles (pH 5-6) by the nicotinyl groups, thus circumventing the use of chloroquine. The results obtained, however, while showing a 5- to 6-fold increase in luciferase transfection activity still necessitated an absolute requirement for chloroquine. A further polylysine conjugate containing a larger number of nicotinyl residues, biotin10-nicotinyl120-polylysine250, also was prepared and studied. This macromolecule stimulated luciferase activity to a small extent and was also dependent on chloroquine. Smaller biotinylated polylysine100 conjugates containing nicotinyl groups were also prepared. These were biotin10-nicotinyl30-polylysine100, and biotin10-nicotinyl60-polylysine100, respectively. Both substances, however, gave opaque, hazy aqueous solutions with precipitates on standing and could not be used for further experimental work. The results indicate that the introduction of weakly basic nicotinyl (pyridine-3-carboxyl) groups onto polylysine250 give conjugates that are unable to replace the lysosomotrophic agent chloroquine in the HeLa cell sysem studied. A 5- to 6-fold increase in luciferase activity, however, was found with biotin10-nicotinyl60-polylysine250.


Carbon nitride-TiO2 hybrid modified with hydrogenase for visible light driven hydrogen production.
A system consisting of a [NiFeSe]-hydrogenase (H2ase) grafted on the surface of a TiO2 nanoparticle modified with polyheptazine carbon nitride polymer, melon (CN x ) is reported. This semi-biological assembly shows a turnover number (TON) of more than 5.8 × 105 mol H2 (mol H2ase)-1 after 72 h in a sacrificial electron donor solution at pH 6 during solar AM 1.5 G irradiation. An external quantum efficiency up to 4.8% for photon-to-hydrogen conversion was achieved under irradiation with monochromatic light. The CN x -TiO2-H2ase construct was also active under UV-free solar light irradiation (λ > 420 nm), where it showed a substantially higher activity than TiO2-H2ase and CN x -H2ase due, in part, to the formation of a CN x -TiO2 charge transfer complex and highly productive electron transfer to the H2ase. The CN x -TiO2-H2ase system sets a new benchmark for photocatalytic H2 production with a H2ase immobilised on a noble- and toxic-metal free light absorber in terms of visible light utilisation and stability.


National Trends in Incidence and Outcomes of Patients With Heart Failure Requiring Respiratory Support.
Despite increasing medical complexity in patients with heart failure (HF), there are limited data on incidence and outcomes for patients with HF needing respiratory support. This study sought to examine contemporary trends of respiratory support strategies among patients with HF. Using the National Inpatient Sample, we identified adults aged greater than 18 years hospitalized with a primary diagnosis of HF. We assessed for trends in the use of invasive mechanical ventilation (IMV) and noninvasive ventilation (NIV), length of stay, hospital costs, and in-hospital mortality. From 2002 to 2014, we identified 9,508,768 HF hospitalizations, which included 202,340 (2.13%) and 257,549 (2.71%) patients that required IMV and NIV, respectively. Over the study period, the proportion of HF patients requiring IMV significantly decreased (3.25% in 2002 to 1.56% in 2014) whereas the use of NIV significantly increased from 0.95% to 7.25% (ptrend <0.001 for both). In-hospital mortality significantly increased for IMV (31.5% in 2002 to 38.6% in 2014) recipients and decreased for patients requiring NIV (9.0% to 5.6%, ptrend <0.0001 for both). The average length of stay was nearly 7 days longer in the IMV group (12.2 days) and 2 days longer in the NIV group (6.8 days; p <0.001 for both). Hospital charges have nearly tripled for patients requiring IMV ($99,358 in 2014, ptrend <0.001) and doubled for those requiring NIV ($37,539 in 2014, ptrend <0.001). In conclusion, respiratory support strategies for patients with HF have significantly evolved with increasing use of NIV as compared with IMV. However, the in-hospital mortality associated with respiratory failure remains unacceptably high.


The histopathological effects of calcium triglyceride bone cement and chitosan on the healing of experimental bone defects
This study evaluated the histopathological effects of two different bone grafts, calcium triglyceride bone cement (CTBC) and chitosan, on the healing of experimental bone defects. Ninety-two Sprague Dawley male rats, with a weight of 240 ± 20 g, were used. Two experimental groups that consisted of 64 rats were divided into four subgroups due to the sacrification days, which were 7, 14, 30, and 60. After creating an 8-mm- long and 1-mm-wide cortico-cancellous bone defect in the right tibia of each rat, CTBC and chitosan were applied to the bone defects. In the main group, after creating the bone defects in the right tibias, we kept those empty to serve as the control group. We evaluated inflammation, foreign body reaction, necrosis, fibrosis, new bone formation, and the residual graft material at 7, 14, 30, and 60 days. In both the CTBC and chitosan groups, the new bone formation was higher than that in the control group, whereas foreign body reaction and residual graft material in the CTBC group and fibrosis in the chitosan group were significantly higher. After evaluating the results, both materials were found not to be very useful in the bone healing process. CTBC remained for a long time without being resorbed; it can be used as a placeholder in large bone defects, whereas the gel form of chitosan cannot be utilized for this purpose because it was resorbed in the first 7 days.


Meta-analysis comparing reported frequency of atrial fibrillation after acute coronary syndromes in Asians versus whites.
The development of atrial fibrillation (AF) in cardiac patients is multifactorial, including not well defined genetic factors. To determine if Asian ethnicity is associated with the development of AF in patients with coronary disease, a meta-analysis was conducted of patient-level data from 7 prospective randomized clinical trials that prospectively collected information on the development of AF: 3 trials in patients with ST-elevation myocardial infarction (Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] I, GUSTO III, and GUSTO V), 3 trials in patients with non-ST-elevation acute coronary syndromes (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy [PURSUIT], Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis-II [IMPACT II], and Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network [PARAGON A]), and 1 trial in patients with both conditions (GUSTO IIb). A total of 94,785 patients were identified (93,050 white, 1,735 Asian). At baseline, Asian patients were younger; had lower body mass indexes; had a lower prevalence of female gender, previous angioplasty, and previous coronary artery bypass grafting; and had a greater prevalence of diabetes compared with white patients. The development of AF was lower in Asian than in white patients (4.7% vs 7.6%, p <0.001), while rates of ventricular tachycardia and fibrillation were similar in the 2 groups. In multivariate logistic regression analysis, Asian ethnicity was associated with significantly lower rates of AF (odds ratio 0.65, 95% confidence interval 0.50 to 0.84, p = 0.001) compared with white ethnicity. In conclusion, similar to previous studies showing a lower incidence of AF in non-Caucasian populations, Asians experiencing acute ischemic syndromes have a significantly lower frequency of AF compared with whites. Further study is needed to investigate the mechanisms and potential genetic underpinnings behind this association.


Model-independent quantitative measurement of nanomechanical oscillator vibrations using electron-microscope linescans.
Nanoscale mechanical resonators are highly sensitive devices and, therefore, for application as highly sensitive mass balances, they are potentially superior to micromachined cantilevers. The absolute measurement of nanoscale displacements of such resonators remains a challenge, however, since the optical signal reflected from a cantilever whose dimensions are sub-wavelength is at best very weak. We describe a technique for quantitative analysis and fitting of scanning-electron microscope (SEM) linescans across a cantilever resonator, involving deconvolution from the vibrating resonator profile using the stationary resonator profile. This enables determination of the absolute amplitude of nanomechanical cantilever oscillations even when the oscillation amplitude is much smaller than the cantilever width. This technique is independent of any model of secondary-electron emission from the resonator and is, therefore, applicable to resonators with arbitrary geometry and material inhomogeneity. We demonstrate the technique using focussed-ion-beam-deposited tungsten cantilevers of radius ~60-170 nm inside a field-emission SEM, with excitation of the cantilever by a piezoelectric actuator allowing measurement of the full frequency response. Oscillation amplitudes approaching the size of the primary electron-beam can be resolved. We further show that the optimum electron-beam scan speed is determined by a compromise between deflection of the cantilever at low scan speeds and limited spatial resolution at high scan speeds. Our technique will be an important tool for use in precise characterization of nanomechanical resonator devices.


Bradykinin-induced amyloid precursor protein secretion: a protein kinase C-independent mechanism that is not altered in fibroblasts from patients with sporadic Alzheimer's disease.
We treated human skin fibroblasts with bradykinin (BK) and observed a concentration-dependent increase in the release of soluble amyloid precursor protein (sAPP). The estimated EC50 for the observed effect is 2.8 nM, which is of the same order of magnitude as the reported Kd of BK binding in human skin fibroblasts. The effect of BK on sAPP secretion appears to be dependent on interaction of the ligand with the B2 type of BK receptors but independent of activation of protein kinase C. We also show that sAPP release after BK treatment in fibroblasts from patients with sporadic Alzheimer's disease is not different from control cells and is paralleled by equivalent levels of inositol trisphosphate production. A discussion of the differences from previously published work focuses on the possible divergent alterations in transduction systems in fibroblasts from patients with familial and sporadic Alzheimer's disease. Our results are the first example of receptor-mediated sAPP release in human skin fibroblasts and the first demonstration of the co-existence of protein kinase C-dependent and -independent mechanisms in these cells.


Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer.
Indoleamine 2,3-dioxygenase (IDO) has recently been proposed to account for tumor-induced immunosuppression by influencing the conversion of tryptophan (Trp) into kynurenine (Kyn). The objective of our study was to correlate IDO activity with disease outcome in non-small cell lung cancer (NSCLC) patients treated with multimodal combination therapy. In a single-arm Phase II trial involving induction gemcitabine and carboplatin followed by concurrent paclitaxel, carboplatin and 74 Gy thoracic radiation in stage III NSCLC patients, plasma was drawn at baseline, post-induction, and post-concurrent therapy. The mean plasma Kyn/Trp ratio was used as a surrogate indicator of IDO activity. The 33 participants were distributed as follows: 15 females, 18 males; median age = 62; median overall survival (OS) = 22.4 (95% CI 19.3-25.1) months; median progression-free survival (PFS) = 11.5 (95% CI 6.7-16.3) months. The mean Kyn/Trp ratio at baseline (4.5 ± 2.8) was higher than that of healthy controls (2.9 ± 1.9, p = 0.03) and increased after induction therapy (5.2 ± 3.2, p = 0.08) and chemoradiation (5.8 ± 3.9, p = 0.01). The post-treatment Kyn/Trp ratio and radiologic responses were not significantly associated at any time point. No significant correlation was found between baseline Kyn/Trp ratios and OS (HR = 1.1, 95% CI 0.45-2.5) or PFS (HR = 0.74, 95% CI 0.30-1.82). A post-induction chemotherapy increase in IDO activity portended worse OS (HR = 0.43, 95% CI 0.19-0.95, p = 0.037) and PFS (HR = 0.47, 95% CI 0.22-1.0, p = 0.055). This observed increase in IDO transcription may be a means for tumors to evade immunosurveillance.


Effects of selective cholinergic antagonists and alpha,beta-methylene ATP on guinea-pig urinary bladder contractions in vivo following pelvic nerve stimulation.
1. An in vivo preparation measuring functional detrusor muscle strength in terms of intravesical bladder pressure (Pves) following in situ pelvic nerve stimulation has been developed in urethane-anaesthetized guinea pigs. 2. The increase in bladder pressure following pelvic nerve stimulation was abolished by topical lidocaine or tetrodotoxin, suggesting a neurogenic origin for the in vivo contractile response. 3. Cholinergic antagonists (i.v.) decreased the amplitude of the peak pressure response by about 50% at both high (30 Hz) and low (5 Hz) stimulation rates, with a rank order of potency of atropine greater than propantheline greater than oxybutynin greater than hexahydrosiladifenidol greater than pirenzepine greater than methoctramine. 4. The P2 purine receptor antagonist, alpha,beta-methylene ATP (i.v.), antagonized pelvic nerve-stimulated bladder contractions differentially at 5 and 30 Hz. At low frequencies, alpha, beta-methylene ATP was both more potent (2.5-fold) and more efficacious (-77 compared to -55% delta) than at 30 Hz. Atropine and alpha,beta-methylene ATP together completely inhibited the contractile response. 5. Together, the findings indicate that in guinea pigs, urinary bladder contractions induced by pelvic nerve stimulation in vivo may be mediated by both muscarinic and purinergic receptors and that these bladder contractions may be mediated by the M2 beta subtype rather than by M1 or M2 alpha muscarinic receptors.


Frontal brain asymmetry in depression with comorbid anxiety: a neuropsychological investigation.
The approach-withdrawal model posits that depression and anxiety are associated with a relative right asymmetry in frontal brain activity. Most studies have tested this model using measures of cortical brain activity such as electroencephalography. However, neuropsychological tasks that differentially use left versus right frontal cortical regions can also be used to test hypotheses from the model. In two independent samples (Study 1 and 2), the present study investigated the performance of currently depressed individuals with or without a comorbid anxiety disorder and healthy controls on neuropsychological tasks tapping primarily left (verbal fluency) or right (design fluency) frontal brain regions. Across both samples, results indicated that comorbid participants performed more poorly than depressed only and control participants on design fluency, while all groups showed equivalent performance on verbal fluency. Moreover, comorbid participants showed "asymmetrical" performance on these two tasks (i.e., poorer design [right frontal] relative to verbal [left frontal] fluency), whereas depressed only and control participants showed approximately symmetrical profiles of performance. Results from these two samples suggest an abnormal frontal asymmetry in neurocognitive performance driven primarily by right frontal dysfunction among anxious-depressed individuals and highlight the importance of considering comorbid anxiety when examining frontal brain functioning in depression.


Species- and Caste-Specific Gut Metabolomes in Fungus-Farming Termites.
Fungus-farming termites host gut microbial communities that contribute to the pre-digestion of plant biomass for manuring the fungal mutualist, and potentially to the production of defensive compounds that suppress antagonists. Termite colonies are characterized by complex division of labor and differences in diet between termite size (minor and major) and morphological (worker and soldier) castes, and this extends to the composition of their gut microbial communities. We hypothesized that gut metabolomes should mirror these differences and tested this through untargeted LC-MS/MS analyses of three South African species of fungus-farming termites. We found distinct metabolomes between species and across castes, especially between soldiers and workers. Primary metabolites dominate the metabolomes and the high number of overlapping features with the mutualistic fungus and plant material show distinct impacts of diet and the environment. The identification of a few bioactive compounds of likely microbial origin underlines the potential for compound discovery among the many unannotated features. Our untargeted approach provides a first glimpse into the complex gut metabolomes and our dereplication suggests the presence of bioactive compounds with potential defensive roles to be targeted in future studies.


Selective EGLN Inhibition Enables Ablative Radiotherapy and Improves Survival in Unresectable Pancreatic Cancer.
When pancreatic cancer cannot be removed surgically, patients frequently experience morbidity and death from progression of their primary tumor. Radiation therapy (RT) cannot yet substitute for an operation because radiation causes fatal bleeding and ulceration of the nearby stomach and intestines before achieving tumor control. There are no FDA-approved medications that prevent or reduce radiation-induced gastrointestinal injury. Here, we overcome this fundamental problem of anatomy and biology with the use of the oral EGLN inhibitor FG-4592, which selectively protects the intestinal tract from radiation toxicity without protecting tumors. A total of 70 KPC mice with autochthonous pancreatic tumors received oral FG-4592 or vehicle control ± ablative RT to a cumulative 75 Gy administered in 15 daily fractions to a limited tumor field. Although ablative RT reduced complications from local tumor progression, fatal gastrointestinal bleeding was observed in 56% of mice that received high-dose RT with vehicle control. However, radiation-induced bleeding was completely ameliorated in mice that received high-dose RT with FG-4592 (0% bleeding, P < 0.0001 compared with vehicle). Furthermore, FG-4592 reduced epithelial apoptosis by half (P = 0.002) and increased intestinal microvessel density by 80% compared with vehicle controls. EGLN inhibition did not stimulate cancer growth, as treatment with FG-4592 alone, or overexpression of HIF2 within KPC tumors independently improved survival. Thus, we provide a proof of concept for the selective protection of the intestinal tract by the EGLN inhibition to enable ablative doses of cytotoxic therapy in unresectable pancreatic cancer by reducing untoward morbidity and death from radiation-induced gastrointestinal bleeding. SIGNIFICANCE: Selective protection of the intestinal tract by EGLN inhibition enables potentially definitive doses of radiation therapy. This might allow radiation to be a surgical surrogate for unresectable pancreatic cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/9/2327/F1.large.jpg.


Effects of a patient's name and image on medical knowledge acquisition.
To assess whether there are differences in medical students' (MS) knowledge acquisition after being provided a virtual patient (VP) case summary with a patient's name and facial picture included compared to no patient's name or image. 76 MS from four clerkship blocks participated. Blocks one and three (Treatment group) were provided case materials containing the patient's name and facial picture while blocks two and four (Control group) were provided similar materials without the patient's name or image. Knowledge acquisition was evaluated with a multiple-choice-question examination (CQA_K). Treatment group CQA_K scores were 64.6% (block one, n = 18) and 76.0% (block three, n = 22). Control group scores were 71.7%, (block two, n = 17) and 68.4% (block four, n = 19). ANOVA F-test among the four block mean scores was not significant; F (3, 72) = 1.68, p = 0.18, η2=0.07. Only 22.2% and 27.3% of the MS from blocks one and three respectively correctly recalled the patient's name while 16.7% and 40.9% recalled the correct final diagnosis of the patient. These results suggest that including a patient's name and facial picture on reading materials may not improve MS knowledge acquisition. Corroborating studies should be performed before applying these results to the design of instructional materials.


Stromal cell heterogeneity in fibroblast growth factor-mediated stromal-epithelial cell cross-talk in premalignant prostate tumors.
Homeostasis of normal prostate and two-compartment nonmalignant prostate tumors is dependent on two-way communication between epithelial and stromal compartments. Independence of epithelial cells on controlling instructions from stroma is a hallmark of extremely malignant epithelial cell tumors. To better understand the evolution of stromal independence during malignant progression, we performed a clonal analysis of stromal cells derived from a well-defined model of two-way stromal-epithelial cell communication that loses response to stroma during prostate tumor progression. Directionally specific signaling from stroma to epithelium contributes to homeostasis between the two compartments. Stromal cells were characterized in respect to expression and activity of isotypes of the fibroblast growth factor (FGF) family of ligands and receptors in addition to morphology and cytoskeletal markers. One stromal subtype (DTS1) exhibited a fibroblast-like morphology and did not display smooth muscle cell (SMC) alpha-actin. The other (DTS2) exhibited SMC alpha-actin and an SMC-like morphology in vitro. Both subtypes expressed FGF7 and equally low levels of FGFR2IIIc mRNA, whereas fibroblast growth factor receptor (FGFR) 1 predominated in DTS1 cells. DTS1 cells also expressed FGF10 and no detectable FGFR3, whereas the absence of FGF10 and presence of FGFR3 distinguished DTS2 cells. Epithelial cell-derived FGF9 bound to FGFR and stimulated growth of specifically FGFR3-positive DTS2 cells, not the FGFR3-negative DTS1 cells. These results demonstrate stromal cell heterogeneity in signal reception of FGF from epithelium. This correlated with potential heterogeneity in the response back to epithelial cells. Epithelium-dependent control of a stromal cell phenotype within a tumor may be a determinant of whether tumors remain in nonmalignant homeostasis or progress to malignancy.


Heart failure, chronic kidney disease, and biomarkers--an integrated viewpoint--.
Chronic kidney disease (CKD) is frequently associated with a progressive decrease in the glomerular filtration rate, which leads to endstage renal disease (ESRD). Heart failure (HF) is a complex syndrome rather than a primary diagnosis, and considered as the endpoint of all cardiovascular disorders. It is the leading cause of death among the cardiovascular diseases in patients with CKD and ESRD. There is some interaction between the heart and kidney (the so-called "cardiorenal syndrome"), and HF patients with the complication of CKD or ESRD show a worse prognosis. Thus, early diagnosis and aggressive management of HF are needed in patients with CKD and ESRD. A number of biomarkers appear to have growing clinical importance and are reported for detection and stratification of HF. Although HF and CKD have a close interrelationship, the utility of the biomarkers has not been adequately studied with regard to the relationship with renal dysfunction. This paper reviews of the current evidence about laboratory biomarkers in patients with HF or CKD, emphasizing the emerging cardiac biomarkers (ie, BNPs and cardiac troponins), and the biomarkers of renal injury (ie, cystatin C and neutrophil gelatinase-associated lipocalin). Furthermore, it discusses the potential role of these markers in terms of heart - kidney interactions and their utility in the diagnostic and therapeutic strategies for cardiorenal syndrome.


Treatment with isolated gold nanoparticles reverses brain damage caused by obesity.
In this study, we performed two experiments. In the first experiment, the objective was to link gold nanoparticles (GNPs) with sodium diclofenac and/or soy lecithin and to determine their concentration in tissues and their toxicity using hepatic and renal analyzes in mice to evaluate their safety as therapeutic agents in the subsequent treatment of obesity. In the second experiment, we evaluated the effect of GNPs on inflammatory and biochemical parameters in obese mice. In the first experiment, we synthesized and characterized 18 nm GNPs that were administered intraperitoneally in isolation or in association with sodium diclofenac and/or soy lecithin in mice once daily for 1 or 14 days. Twenty-four hours after the single or final administration, the animals were euthanized, following which the tissues were removed for evaluating the concentration of GNPs, and serum samples were collected for hepatic and renal analysis. Hepatic damage was evaluated based on the levels of alanine aminotransferase (ALT), whereas renal damage was evaluated based on creatinine levels. A higher concentration of GNPs was detected in the tissues upon administration for 14 days, and there were no signs of hepatic or renal damage. In the second experiment, the mice were used as animal models of obesity and were fed a high-fat diet (obese group) and control diet (control group). After eight weeks of high-fat diet administration, the mice were treated with saline or with GNPs (average size of 18 nm) at a concentration of 70 mg/L (70 mg/kg) once a day, for 14 days, for 10 weeks. Body weight and food intake were measured frequently. After the experiment ended, the animals were euthanized, serum samples were collected for glucose and lipid profile analysis, the mesenteric fat content was weighed, and the brains were removed for inflammatory and biochemical analysis. In obese mice, although GNP administration did not reduce body and mesenteric fat weight, it reduced food intake. The glucose levels were reversed upon administration of GNPs, whereas the lipid profile was not altered in any of the groups. GNPs exerted a beneficial effect on inflammation and oxidative stress parameters, without reverting mitochondrial dysfunction. Our results indicate that the intraperitoneal administration of GNPs for 14 days results in a significant GNP concentration in adipose tissues, which could be an interesting finding for the treatment of inflammation associated with obesity. Based on the efficacy of GNPs in reducing dietary intake, inflammation, and oxidative stress, they can be considered potential alternative agents for the treatment of obesity.


Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats.
The effects of high-sodium (HS) and normal-sodium (NS) diets on ovarian hormone modulation of mean arterial pressure (MAP) were examined in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Ovariectomy increased MAP (OVX-Sham) to a greater extent in DS rats maintained for 2 wk on a HS (22 mmHg) compared with a NS (6 mmHg) diet. Ovariectomy had no effect on MAP in DR rats on NS but did increase MAP in rats on HS (10 mmHg) diets. On HS diets, glomerular filtration rate (GFR) was 36% less in the DS-Sham than DR-Sham animals; ovariectomy increased GFR in both strains by 1.4-1.5-fold; glomerular angiotensin II type 1 receptor (AT(1)R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT(1)R densities by 1.3-fold in DR rats but had no effect in DS rats; 17beta-estradiol (E(2)) downregulated adrenal AT(1)R densities in both strains on either diet; ovariectomy reduced estrogen receptor-alpha (ER-alpha) protein expression in the renal cortex by 40-50% although renal ER-alpha expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E(2) treatment, suggesting that E(2) deficiency mediates the effects of ovariectomy on MAP, GFR, AT(1)R densities, and renal ER-alpha protein expression. In conclusion, ovariectomy-induced increases in MAP are augmented by HS diet in both strains, and this effect is not mediated by a reduction in GFR. Aberrant renal AT(1)R regulation and reduced renal ER-alpha expression are potential contributors to the hypertensive effects of E(2) deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E(2) deficient, such as postmenopausal women.


Axon injury and regeneration in the adult Drosophila.
Neural regeneration is a fascinating process with profound impact on human health, such that defining biological and genetic pathways is of interest. Here we describe an in vivo preparation for neuronal regeneration in the adult Drosophila. The nerve along the anterior margin of the wing is comprised of ~225 neurons that send projections into the central neuropil (thorax). Precise ablation can be induced with a pulsed laser to sever the entire axonal tract. The animal can be recovered, and response to injury assessed over time. Upon ablation, there is local loss of axons near the injury site, scar formation, a rapid impact on the cytoskeleton, and stimulation of hemocytes. By 7d, ~50% of animals show nerve regrowth, with axons from the nerve cells extending down towards the injury or re-routing. Inhibition of JNK signaling promotes regrowth through the injury site, enabling regeneration of the axonal tract.


A Highly Sensitive Urinary Exosomal miRNAs Biosensor Applied to Evaluation of Prostate Cancer Progression.
Prostate cancer is the most common cancer in the male population, carrying a significant disease burden. PSA is a widely available screening tools for this disease. Current screen-printed carbon electrode (SPCE)-based biosensors use a two-pronged probe approach to capture urinary miRNA. We were able to successfully detect specific exosomal miRNAs (exomiRs) in the urine of patients with prostate cancer, including exomiR-451 and exomiR-21, and used electrochemistry for measurement and analysis. Our results significantly reaffirmed the presence of exomiR-451 in urine and that a CV value higher than 220 nA is capable of identifying the presence of disease (p-value = 0.005). Similar results were further proven by a PAS greater than 4 (p-value = 0.001). Moreover, a higher urinary exomiR-21 was observed in the high-T3b stage; this significantly decreased following tumor removal (p-values were 0.016 and 0.907, respectively). According to analysis of the correlation with tumor metastasis, a higher exomiR-21 was associated with lymphatic metastasis (p-value 0.042), and higher exomiR-461 expression was correlated with tumor stage (p-value 0.031), demonstrating that the present exomiR biosensor can usefully predict tumor progression. In conclusion, this biosensor represents an easy-to-use, non-invasive screening tool that is both sensitive and specific. We strongly believe that this can be used in conjunction with PSA for the screening of prostate cancer.


Modern-Day Practice of DCD Liver Transplantation: Controversies, Innovations, and Future Directions.
Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement. New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts. As these modalities enter routine clinical practice, DCD utilization will continue to increase, and liver allocation policies in turn will evolve to reflect this growing practice. This review describes recent progress in DCD LT, current challenges with utilization of DCD liver allografts, and how novel technologies and policies could impact the future of the field.


Activation of rat liver microsomal glutathione transferase by hepsin.
Rat liver microsomal glutathione transferase (MGST1) is activated by limited proteolysis. Recently we purified a protease, hepsin, from rat liver microsomes that activates MGST1. In the present study the mechanism of MGST1 activation by hepsin was investigated. When MGST1 and hepsin were incubated at room temperature, MGST1 activity was markedly increased and the increase was decreased to the control level by further incubation with disulfide bond reducing agent dithiothreitol. MGST1 dimer was detected by electrophoresis after treatment of MGST1 with hepsin, instead of proteolytic product. MGST1 dimer formation accompanied by an increase in MGST1 activity was observed even in the presence of the protease inhibitor benzamidine. Furthermore, prolonged incubation of both enzymes caused the formation of MGST1 dimer and its proteolytic product. These results clearly show that the protease hepsin stimulates disulfide-linked MGST1 dimer formation resulting in activation of MGST1 and preferential degradation of MGST1 dimer. Since hepsin contains disulfide bonds in the scavenger receptor cysteine-rich (SRCR) domain, it was suggested that the SRCR domain interacts with MGST1 leading to thiol/disulfide exchange between the two enzymes followed by disulfide-linked MGST1 dimer formation.


Mitochondrial adaptations to utilize hydrogen sulfide for energy and signaling.
Sulfur is a versatile molecule with oxidation states ranging from -2 to +6. From the beginning, sulfur has been inexorably entwined with the evolution of organisms. Reduced sulfur, prevalent in the prebiotic Earth and supplied from interstellar sources, was an integral component of early life as it could provide energy through oxidization, even in a weakly oxidizing environment, and it spontaneously reacted with iron to form iron-sulfur clusters that became the earliest biological catalysts and structural components of cells. The ability to cycle sulfur between reduced and oxidized states may have been key in the great endosymbiotic event that incorporated a sulfide-oxidizing α-protobacteria into a host sulfide-reducing Archea, resulting in the eukaryotic cell. As eukaryotes slowly adapted from a sulfidic and anoxic (euxinic) world to one that was highly oxidizing, numerous mechanisms developed to deal with increasing oxidants; namely, oxygen, and decreasing sulfide. Because there is rarely any reduced sulfur in the present-day environment, sulfur was historically ignored by biologists, except for an occasional report of sulfide toxicity. Twenty-five years ago, it became evident that the organisms in sulfide-rich environments could synthesize ATP from sulfide, 10 years later came the realization that animals might use sulfide as a signaling molecule, and only within the last 4 years did it become apparent that even mammals could derive energy from sulfide generated in the gastrointestinal tract. It has also become evident that, even in the present-day oxic environment, cells can exploit the redox chemistry of sulfide, most notably as a physiological transducer of oxygen availability. This review will examine how the legacy of sulfide metabolism has shaped natural selection and how some of these ancient biochemical pathways are still employed by modern-day eukaryotes.


Differences in spatio‑temporal distribution of the visual P3b event-related potential between young men and women.
Here, we evaluated the P3b potential evoked in a visual two-stimulus oddball paradigm. The experiment was conducted in 20 healthy students (23.1±1.1 years, 10 women), using a 32 channel electroencephalography (EEG) montage system. The paradigm included geometric figures; a black square on a white background as a target and a white circle on a black background as a standard stimulus. We examined the maximal amplitude and latency of the P3b component at 18 electrode sites, as well as, temporal changes of scalp voltage distribution. We observed a non-equal spatial distribution of the visual ERP (event related potentials) waveforms on the scalp surface, with the highest P3b waveform observed over midline parietal areas and the lowest over frontal regions. Moreover, the spatial distribution of ERP signal on the scalp surface was more lateralized towards the right side in men and more centralized in women. Gender-related differences in P3b amplitude and latency were observed only in left hemisphere. Differences in P3b between men and women observed in our study arose not only from different P3b amplitudes and latencies, but also from the speed and character of P3b waveform fall, resulting in spatio-temporal amplitude changes. Moreover, the spatial distribution of the P200 potential also changed on the scalp differently in men and women. These results suggest that gender-related differences evoked in visual two-stimulus oddball paradigm, which engage attention processes, are complex and include spatio-temporal changes in P3b waveform generation, distribution, and suppression across the scalp.


Selective abnormalities of azurophil and specific granules of human neutrophilic leukocytes.
Human neutrophilic granulocytes (PMN) contain two chemically distinct granule types, which appear at different stages of maturation. The azurophilic granule (or primary granule) is formed during the promyelocyte stage and is known to contain myeloperoxidase in addition to numerous lysosomal enzymes, neutral proteases, glycoaminoglycans, cationic bactericidal proteins, and lysozyme. The specific granule (or secondary granule) is formed during the myelocyte stage. It is defined by the absence of peroxidase and has been shown to contain lysozyme, lactoferrin, and B12-binding proteins. The mature PMN contains both types of granules: 33% azurophilic and 67% specific granules. There are now a few well-documented examples of pathological PMN granulations that can be classified as a selective abnormality of one granule type or the other.


Incorporation of 2,3-diaminopropionic acid into linear cationic amphipathic peptides produces pH-sensitive vectors.
Nonviral vectors that harness the change in pH in endosomes, are increasingly being used to deliver cargoes, including nucleic acids, into mammalian cells. Here we present evidence that the pK(a) of the beta-NH(2) in 2,3-diaminopropionic acid (Dap) is sufficiently lowered, when Dap is incorporated into peptides, that its protonation state is sensitive to the pH changes that occur during endosomal acidification. The lowered pK(a) of around 6.3 is stabilized by the increased electron-withdrawing effect of the peptide bonds, by intermolecular hydrogen bonding and from contributions arising from the peptide conformation. These include mixed polar/apolar environments, Coulombic interactions and intermolecular hydrogen bonding. Changes in the charged state are therefore expected between pH 5 and 7, and large-scale conformational changes are observed in Dap-rich peptides, in contrast to analogues containing lysine or ornithine, when the pH is altered through this range. These physical properties confer a robust gene-delivery capability on designed cationic amphipathic peptides that incorporate Dap.


Changes in diaphragmatic EMG spectra during hyperpneic loads.
Changes in electromyographic (EMG) activity of the diaphragm were examined in human subjects during different levels of voluntary hyperpnea. Diaphragmatic EMG was recorded using both surface and esophageal electrodes. The power spectra density (PSD) of the EMG signal was calculated and characterized by the high frequency to low frequency (H/L) ratio and by the centroid frequency (Fc). During high levels of voluntary hyperpnea, a significant decrease in both the H/L ratio and Fc occurred, which was similar in diaphragmatic EMG recorded by either surface or esophageal electrodes. This similarity in EMG spectral changes suggested that when diaphragmatic EMG was recorded using surface electrodes, there was only minimal contamination from the activity of other chest wall muscles. Changes in EMG Fc were detected during levels of hyperpnea which could be readily sustained. Thus, diaphragmatic EMG spectral changes were not characteristic of imminent ventilatory failure (i.e., an inability to sustain a target level of ventilation). In contrast, significant changes in EMG H/L ratio were observed only during hyperpneic loads which could not be sustained. This difference in sensitivity between the Fc and H/L ratio was due to the increased variability of H/L ratio and suggests that the H/L ratio may fail to detect small but significant shifts in EMG spectra. The relationship between the rate of decrease in EMG Fc and the level of hyperpnea was not statistically significant. We conclude that diaphragmatic EMG spectral changes do occur during hyperpneic loads, but we question the specificity of using diaphragmatic EMG spectral changes in predicting ventilatory failure.


Time-dependent effects of ultraviolet and nonthermal atmospheric pressure plasma on the biological activity of titanium.
Here, we evaluated time-dependent changes in the effects of ultraviolet (UV) and nonthermal atmospheric pressure plasma (NTAPPJ) on the biological activity of titanium compared with that of untreated titanium. Grade IV machined surface titanium discs (12-mm diameter) were used immediately and stored up to 28 days after 15-min UV or 10-min NTAPPJ treatment. Changes of surface characteristics over time were evaluated using scanning electron microscopy, surface profiling, contact angle analysis, X-ray photoelectron spectroscopy, and surface zeta-potential. Changes in biological activity over time were as determined by analysing bovine serum albumin adsorption, MC3T3-E1 early adhesion and morphometry, and alkaline phosphatase (ALP) activity between groups. We found no differences in the effects of treatment on titanium between UV or NTAPPJ over time; both treatments resulted in changes from negatively charged hydrophobic (bioinert) to positively charged hydrophilic (bioactive) surfaces, allowing enhancement of albumin adsorption, osteoblastic cell attachment, and cytoskeleton development. Although this effect may not be prolonged for promotion of cell adhesion until 4 weeks, the effects were sufficient to maintain ALP activity after 7 days of incubation. This positive effect of UV and NTAPPJ treatment can enhance the biological activity of titanium over time.


LyP-1 ultrasonic microbubbles targeting to cancer cell as tumor bio-acoustics markers or drug carriers: targeting efficiency evaluation in, microfluidic channels.
Using ultrasonic contrast microbubbles as acoustic biomarkers and drug carrier vehicles by conjugating tumor specific antibody to microbubbles has shown great potential in ultrasonic tumor molecular imaging or drug-delivery and therapy. Microbubble probe targeting efficiency is one of the major challenges. In this study, we developed a novel method to evaluate the targeting capability and efficiency of microbubbles to cells, and more specifically, microbubbles binding LyP-1 (a cyclic nonapeptide acid peptide) target to cancer cell within a microfluidic system. The micro cell sieves within the microfludic channels could trap the tumor cells and enhance the microbubble's interaction with the cell. Assisted with the controllable fluid shear stress, the microbubble's targeting to the cell and the corresponding affinity efficiency could be quantitatively evaluated under a florescent microscope. The system provides a useful low-cost high efficient in vitro platform for studying microbubble-cell interaction for ultrasonic tumor molecular imaging or drug-delivery and therapy.


Nitrogenase reductase: A functional multigene family in Rhizobium phaseoli.
The complete coding sequence of the nitrogenase reductase gene (nifH) is present in three different regions of a Rhizobium phaseoli symbiotic plasmid. Homology between two of the regions containing nifH coding sequences extends over 5 kilobases. These in turn share 1.3 kilobases of homology with the third region. The nucleotide sequences of the three nitrogenase reductase genes were found to be identical. Site-directed insertion mutagenesis indicated that none of the three genes is indispensable for nitrogen fixation during symbiosis with Phaseolus vulgaris. This implies that at least two of the reiterated genes can be functionally expressed.


The Guide to expression of uncertainty in measurement approach for estimating uncertainty: an appraisal.
The aim of the Guide to Expression of Uncertainty in Measurement (GUM) is to harmonize the different practices for estimating and reporting uncertainty of measurement. Although there are clear advantages in having a common approach for evaluating uncertainty, application of the GUM approach to chemistry measurements is not straightforward. In the above commentary, Krouwer suggests that the GUM approach should not be applied to diagnostic assays, because (a) the quality of diagnostic assays is to low, and (b) the GUM uncertainty intervals are too narrow to predict the outliers that occasionally trouble these methods. Some of the examples presented by Krouwer are reviewed. Sodium measurements are modeled mathematically to illustrate the GUM approach to uncertainty. A standardized uncertainty evaluation process is presented. Modeling of sodium measurements demonstrates how the GUM uncertainty interval reflects the treatment of a bias: The width of the uncertainty interval varied depending on whether a correction for a calibrator lot bias was applied, but in both cases it was consistent with the distribution of measurement results. Expanding the uncertainty interval to include outliers runs counter to the definition of uncertainty. Used appropriately, the GUM uncertainty can be helpful in detecting outliers. In standardizing the uncertainty evaluation, the importance of the analytical imprecision and traceability was emphasized. It is problematic that manufacturers of commercial assays rarely inform about the uncertainty of the values assigned to the calibrators. As demonstrated by an example, external quality-assurance data may be used to estimate this uncertainty. The GUM uncertainty should be applied to measurements in laboratory medicine because it may actually support the forces that drive the work on improving the quality of measurement procedures. However, it is important that the GUM approach is made more manageable by standardizing the uncertainty evaluation procedure as much as possible. It is essential to focus on the traceability and uncertainty of calibrators and reagents supplied by manufacturers of assays. Information about uncertainty is necessary in the evaluation of the uncertainty associated with manufacturers' measurement procedures, and in general it may force manufacturers to increase their efforts in improving the metrologic and analytical quality of their products.