[The long-term patency rate of saphenous vein grafts and vein graft disease in Japanese patients].
While annual attrition and high break-down rate of saphenous vein graft (SVG) used for CABG has widely noted in Western countries, no sizable studies have yet available in Japan. We studied 142 SVGs of 77 pts, which we divided into two groups; 80 SVGs of 44 pts in mid-term period (5 to 8 years after surgery) and 62 SVGs of 33 pts in long-term period (9 to 17 years after surgery). The patency rate of SVGs was 69% in mid-term and 77% in long-term. Whereas these patency rates at each periods were superior to those reported from USA and European countries, a quarter of SVGs in mid-term period and a half in long-term period had significant stenotic changes (over 50%). Of patent SVGs, diseased SVGs reached 36% in mid-term period and 73% in long-term period. In conclusion, although the patency rate of SVGs in Japanese patients was higher than that of the Western countries, vein graft disease apparently occurred in a large proportion of patent SVGs.


Randomized controlled trial of a lay-facilitated angina management programme.
This article reports a randomized controlled trial of lay-facilitated angina management (registered trial acronym: LAMP). Previously, a nurse-facilitated angina programme was shown to reduce angina while increasing physical activity, however most people with angina do not receive a cardiac rehabilitation or self-management programme. Lay people are increasingly being trained to facilitate self-management programmes. A randomized controlled trial comparing a lay-facilitated angina management programme with routine care from an angina nurse specialist. Participants with new stable angina were randomized to the angina management programme (intervention: 70 participants) or advice from an angina nurse specialist (control: 72 participants). Primary outcome was angina frequency at 6 months; secondary outcomes at 3 and 6 months included: risk factors, physical functioning, anxiety, depression, angina misconceptions and cost utility. Follow-up was complete in March 2009. Analysis was by intention-to-treat; blind to group allocation. There was no important difference in angina frequency at 6 months. Secondary outcomes, assessed by either linear or logistic regression models, demonstrated important differences favouring the intervention group, at 3 months for: Anxiety, angina misconceptions and for exercise report; and at 6 months for: anxiety; depression; and angina misconceptions. The intervention was considered cost-effective. The angina management programme produced some superior benefits when compared to advice from a specialist nurse.


Determination of rupatadine in pharmaceutical formulations by a validated stability-indicating MEKC method.
A stability-indicating MEKC was developed and validated for the analysis of rupatadine in tablet dosage forms, using nimesulide as internal standard. The MEKC method was performed on a fused-silica capillary (50 microm id; effective length, 40 cm). The BGE consisted of 15 mM borate buffer and 25 mM anionic detergent SDS solution at pH 10. The capillary temperature was maintained at 35 degrees C and the applied voltage was 25 kV. The injection was performed using the hydrodynamic mode at 50 mbar for 5 s, with detection by photodiode array detector set at 205 nm. The method was linear in the range of 0.5-150 microg/mL (r2=0.9996). The specificity and stability-indicating capability of the method were proven through degradation studies inclusive by MS, and showing also that there was no interference of the excipients and no increase of the cytotoxicity. The accuracy was 99.98% with bias lower than 1.06%. The LOD and LOQ were 0.1 and 0.5 microg/mL, respectively. The proposed method was successfully applied for the quantitative analysis of rupatadine in pharmaceutical formulations, and the results were compared to a validated RP-LC method, showing non-significant difference (p>0.05).


Evaluation of particle gel immunoassays for the detection of severe immunoglobulin A deficiency and anti-human immunoglobulin A antibodies.
Immunoglobulin A (IgA)-deficient patients with anti-IgA (Ab) require transfusions using blood components with less than 0.05 mg IgA/dL as they are known to be safe for these patients. Identification of severely IgA-deficient (IgA SD) donors involved preliminary screening by the Ouchterlony double immunodiffusion assay followed by confirmatory testing at the required level of sensitivity for IgA and Ab at an external reference laboratory. Two in vitro particle gel immunoassays (ID-PaGIA IgA deficiency test and anti-IgA test) were also evaluated for their suitability in identifying IgA SD individuals and determining their Ab status. Samples from 198 donors and 36 patients, subjected to confirmatory testing for IgA SD and Ab over a 2-year period, were also evaluated using the ID-PaGIA kits. DiaMed test sensitivity and specificity for detection of IgA SD in donors was 98% whereas for Ab, test sensitivity was 91% at a specificity of 94%. In patients, sensitivity was 94% for IgA SD and 67% for Ab, both tests at a specificity of 100%. The ID-PaGIA IgA deficiency test was a sensitive and specific tool for identifying IgA SD donors or patients. Sensitivity of the Ab test was high for donors but reduced for patients and of high specificity in both groups. Further studies with patients are needed to confirm this latter observation. Implementation of these tests would make it possible to supply appropriate products from IgA SD donors to prevent anaphylactic transfusion reactions in patients.


Observation of Lamb shift and modified spontaneous emission dynamics in the YBO3:Eu3+ inverse opal.
The study of Lamb shift plays a unique role in quantum electrodynamics because it provides an excellent test of the theory on photonic crystals (PCs). In this Letter, we present the first observation of large Lamb shift in the YBO(3):Eu(3+) inverse opals fabricated by the polystyrene templating method. In addition, it is very interesting to observe that the luminescent dynamics of Eu(3+) decayed with a faster power law (t(-3)), followed by a slower exponential process due to the coexistence of the diffusion field and the propagating field in the PCs.


A Longer Route to the PICU Can Lead to a Longer Stay in the PICU: A Single-Center Retrospective Cohort Study.
Admission to the pediatric ICU versus general pediatric floor for patients is a significant triage decision for emergency department physicians. Escalation of care within 24 hours of hospital admission is considered as a quality metric for pediatric E.R. There exists, however, a lack of data to show that such escalation leads to a poor outcome. A retrospective cohort study was conducted to compare outcomes of patients who required escalation of care within 24 hours of hospital admission to the pediatric ICU (cases) from 01/01 2015 to 02/28 2019 with those who were directly admitted from emergency department to the PICU (controls). A total of 327 cases were compared to 931 controls. Univariate and multivariable regression analysis was done to compare the length of stay and mortality data. Patients who required escalation of care were significantly younger (median age 1.9 years compared to 4.6 years for controls) and had lower severity of illness score (PIM 3). Cases had a much higher proportion of respiratory diagnosis. ICU length of stay, hospital length of stay and the direct cost was significantly higher for cases compared to controls. This difference persisted for all age groups and respiratory diagnosis. The cost of care, however, was only different for 1-5 years and >5 years age groups. The difference in ICU length of stay (Δ11.1%) and hospital length of stay (Δ7.8%) persisted on multivariate regression analysis after controlling for age, sex, PIM3 score, and diagnostic variables. There was no difference in mortality on the univariate or multivariate analysis between the 2 groups. Patients who required escalation of care within 24 hours of hospital admissions have more prolonged ICU and hospital stay and potentially increased cost of care. This measure should be considered while making patient disposition decisions in the emergency department.


Comprehensive Metabolic Profiling of MYC-Amplified Medulloblastoma Tumors Reveals Key Dependencies on Amino Acid, Tricarboxylic Acid and Hexosamine Pathways.
Reprograming of cellular metabolism is a hallmark of cancer. Altering metabolism allows cancer cells to overcome unfavorable microenvironment conditions and to proliferate and invade. Medulloblastoma is the most common malignant brain tumor of children. Genomic amplification of MYC defines a subset of poor-prognosis medulloblastoma. We performed comprehensive metabolic studies of human MYC-amplified medulloblastoma by comparing the metabolic profiles of tumor cells in three different conditions-in vitro, in flank xenografts and in orthotopic xenografts in the cerebellum. Principal component analysis showed that the metabolic profiles of brain and flank high-MYC medulloblastoma tumors clustered closely together and separated away from normal brain and in vitro MYC-amplified cells. Compared to normal brain, MYC-amplified medulloblastoma orthotopic xenograft tumors showed upregulation of the TCA cycle as well as the synthesis of nucleotides, hexosamines, amino acids and glutathione. There was significantly higher glucose uptake and usage in orthotopic xenograft tumors compared to flank xenograft tumors and cells in culture. In orthotopic tumors, glucose was the main carbon source for the de novo synthesis of glutamate, glutamine and glutathione through the TCA cycle. In vivo, the glutaminase II pathway was the main pathway utilizing glutamine. Glutathione was the most abundant upregulated metabolite in orthotopic tumors compared to normal brain. Glutamine-derived glutathione was synthesized through the glutamine transaminase K (GTK) enzyme in vivo. In conclusion, high MYC medulloblastoma cells have different metabolic profiles in vitro compared to in vivo, and key vulnerabilities may be missed by not performing in vivo metabolic analyses.


Myocardial hibernation: a clinician's perspective.
Patients with myocardial hibernation have reversible left ventricular dysfunction after revascularization. Viability testing can identify those patients whose left ventricular dysfunction is primarily due to hibernation rather than scar. Patients with a substantial amount of hibernating myocardium seem to have a better outcome with revascularization than medical therapy. Patients with poor viability do worse after revascularization than patients with good viability.


Performance and Integration of Smartphone Wireless ECG Monitoring into the Enterprise Electronic Health Record: First Clinical Experience.
Patient initiated, remote cardiac monitoring has proved to be a significant advance in the diagnosis and management of arrhythmias. Further improvements in ease of use and access to results will further improve health outcomes and cost-effectiveness. Here we describe a proof-of-concept evaluation to assess the feasibility of successfully implementing a cloud-based management system using KardiaPro (KP) for remote electrocardiogram (ECG) monitoring to interface into EPIC, an enterprise electronic health record (EHR) system. The KP management system was embedded using hypertext markup language (HTML) code directly into the EHR. Encrypted credentials and patient data were bundled with an application programming interface key allowing linkage of remote monitoring from patients' smartphones. During the time of implementation, a total of 322 patients and 32 179 ECGs were recorded. The KP-EHR interface provided full functionality, allowing detection, interpretation and documentation of atrial fibrillation (AF), flutter events, ventricular tachycardia, and complete heart block. Our study focused on KP's detection of AF, and 16.7% of tracings were classified as probable AF with only 2.3% of tracings not analyzed by the KP algorithm because of tracings that were too noisy or truncated. Enhanced management was facilitated with clinical information immediately accessible. Blinded physician ECG review validated the KP proprietary algorithm interpretation and ECGs. Direct integration of KP into EHR was successful and practical. It allows for historical, point of care and immediate retrieval of remote ambulatory monitoring data and documentation into the electronic health record. KP EHR integration warrants further study as it has the potential to improve cost-effectiveness and clinical diagnostic value, leading to improvements in delivery of patient care.


Integration of NMR and high-throughput screening.
NMR-based screening has become a powerful method for the identification and analysis of low-molecular weight organic compounds that bind to protein targets and can be utilized in drug discovery programs. In particular, heteronuclear NMR-based screening can yield information about both the affinity and binding location of potential lead compounds. In addition, heteronuclear NMR-based screening has wide applications in complementing and facilitating conventional high-throughout screening programs. This article will describe several strategies for the integration of NMR-based screening and high-throughput screening. The marriage of these two techniques promises to be of tremendous benefit in the triage of hits that come from HTS, and can aid the medicinal chemist in the identification of quality leads that have high potential for further optimization.


Secretory ribonucleases are internalized by a dynamin-independent endocytic pathway.
Cytosolic internalization is a requirement for the toxicity of secretory ribonucleases. Here, we investigate the mechanism of internalization of Onconase (ONC), a toxic protein, and ribonuclease A (RNase A), a nontoxic homolog. Microscopy studies indicate that both ribonucleases readily bind to the cell surface and are internalized via acidic vesicles. Blocking dynamin-dependent endocytosis prevents transferrin internalization but does not hinder RNase A internalization. ONC and G88R RNase A, which is a toxic variant, demonstrate enhanced cytotoxicity in the absence of clathrin- and dynamin-mediated endocytosis. The cytosolic entry of ribonucleases does not require an acidic environment or transport to the ER and probably occurs from endosomes. Thus, common proteins - secretory ribonucleases - enter the cytosol by a pathway that is distinct from that of other known toxins.


Toxicity study of chitosan administered in feed to Sprague Dawley [Crl:CD(SD)] rats.
Chitosan is a cationic carbohydrate polymer that is commercially derived from the deacetylation of chitin obtained from seafood shells. The most widespread route of human exposure to chitosan is as a dietary supplement for body weight reduction. Chitosan was nominated by the National Cancer Institute for mechanistic studies designed to measure the potential for vitamin E depletion and osteoporosis following ingestion. Male and female Sprague Dawley rats were exposed to chitosan (86.5% deacetylated, with an average molecular weight of approximately 82 kilodaltons and estimated to be approximately 94% pure) in feed for 6 months. (Abstract Abridged).


Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant.
Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and the endothelial cell-binding domain D5. Immobilization of HK to cellular structures plays a central role in activation of the human contact system. SIC was found to inhibit the binding of HK to endothelial cells, and to reduce contact activation as measured by prolonged blood clotting time and impaired release of bradykinin. These results suggest that SIC modifies host defence systems, which may contribute to the virulence of S. pyogenes strains of the M1 serotype.


Cardiac arrest from postpartum spontaneous coronary artery dissection.
We present the case of a 32-year-old woman who presented to the emergency department with a witnessed cardiac arrest. She was otherwise healthy with no cardiac risk factors and had undergone an uneventful repeated cesarean section 3 days priorly. The patient underwent defibrillation, out of ventricular fibrillation to a perfusing sinus rhythm, and was taken to the catheterization laboratory where coronary angiography findings showed spontaneous dissection of the left anterior descending artery. The patient received a total of 6 stents during her hospital stay and was eventually discharged in good condition. Spontaneous coronary artery dissection is a rare entity with a predilection for pregnant or postpartum women. Early diagnosis and treatment are key for survival, and when identified early, mortality rate is reduced.


Combinatorial peptide library for the analysis of antigen recognition by T cells.
Peptides that consist of 19 residues with random sequences (X19) were considered to deliver antigenic stimuli to CD4T cells. When IL-4, IL-7, IL-9, IL-15 and agonistic Ab to CD29 were co-cultured with single peripheral CD4T cells in the presence of X19 and feeder cells, T cells exhibited clonal expansion. These T cell clones showed heterogeneous proliferation patterns against KGXXXXXXXXXGK-based and KGXXXXXXXXXGKGKK-based combinatorial peptide libraries. Pattern-match search on one of the T cell clones resulted in peptide ligand candidates, one of which induced proliferation, as did protein molecules carrying the corresponding sequence. Combinatorial chemistry was useful in determining not only peptide ligands but also peptide superagonists. For this purpose, use of reverse-phase hydrophobic interaction chromatography and mass spectrometry analysis was efficient. Detailed methods are described in the paper.


Brain-type natriuretic peptide and right ventricular end-diastolic volume index measurements are imprecise estimates of circulating blood volume in critically ill subjects.
Surrogate indicators have often been used to estimate intravascular volume to guide fluid management. Brain-type natriuretic peptide (BNP) has been used as a noninvasive adjunct in the diagnosis of fluid overload and as a marker of response to therapy, especially in individuals with congestive heart failure. Similarly, right ventricular end-diastolic volume index (RVEDVI) measurements represent another parameter used to guide fluid resuscitation. The aim of this study was to evaluate whether BNP and RVEDVI are clinically valuable parameters that can distinguish among hypovolemia, euvolemia, and hypervolemia, as measured by blood volume (BV) analysis in critically ill surgical subjects. This observational study was part of a prospective, randomized controlled trial. Subjects with pulmonary artery catheters for the treatment of traumatic injuries, severe sepsis/septic shock, cardiovascular collapse, adult respiratory distress syndrome, and postsurgical care were studied. Circulating BV was measured by a radioisotope dilution technique using the BVA-100 Analyzer (Daxor Corporation, New York, NY) within the first 24 hours of acute resuscitation. BV results were reported as percent deviation from the patient's ideal BV based on height and percent deviation from optimum weight. Hypovolemia was defined as less than 0%, euvolemia was defined as 0% to +16%, and hypervolemia was defined as greater than +16% deviation from ideal BV. RVEDVI was measured by continuous cardiac output pulmonary artery catheters (Edwards Lifesciences, Irvine, CA). BNP and RVEDVI measurements obtained with BV analysis were evaluated with Fisher's exact test and regression analysis. In 81 subjects, there was no difference in BV status between those with BNP of 500 pg/mL or greater and BNP of less than 500 pg/mL (p = 0.82) or in those with RVEDVI of 140 mL/m or greater and RVEDVI of less than 140 mL/m (p = 0.43). No linear relationship existed between BV and these parameters. In critically ill surgical patients, BNP and RVEDVI were not associated with intravascular volume status, although they may be useful as indices that reflect increased cardiac preload. Diagnostic study, level III.


A Meta-Analysis of the Efficacy of Virtual Reality and In Vivo Exposure Therapy as Psychological Interventions for Public Speaking Anxiety.
Public speaking anxiety (PSA) is a prevalent condition with disabling occupational, educational, and social consequences. Exposure therapy is a commonly utilized approach for treating PSA. Traditionally, this intervention has been delivered as in vivo exposure therapy (IVET). Limitations inherent to in vivo as a mode of delivery have been identified and studies have increasingly explored the use of Virtual Reality Exposure Therapy (VRET) as an alternative. Understanding the efficacy of both VRET and IVET as psychological interventions for PSA is important. A systematic search identified 11 studies with 508 participants. Meta-analysis yielded a large significant effect wherein VRET resulted in significant reductions in PSA versus control of -1.39 (Z = 3.96, p < .001) and a similar large significant effect wherein IVET resulted in significant reductions in PSA versus control of -1.41 (Z = 7.51, p < .001). Although IVET was marginally superior to VRET, both interventions proved efficacious. Given the advantages of utilizing VRET over IVET future research and clinical practice could explore VRET as a treatment option for PSA.


Assessing Older Community Members Using a Social Work Tool: Developing an Organizational Response.
Social Worker's undertake psycho-social assessments and facilitate access to evidence-informed psychological and practical supports to optimize the physical, psychological, and social wellbeing of the community members in their care. Social workers employed at an aged and community care organization undertook a review of the gray and peer reviewed literature and did not identify any existing evidence-based tools. However, 10 key domains were identified from the search. Gaps in the domains were discovered, together with the need for guidance and prompts for less experienced staff and students. Five Social Workers, using co-design principles, reviewed the domains, and added further domains from their social work practice. An evidence-based assessment tool was developed which incorporated 11 domains. The tool can be used to assess the needs of people living in the community who are older and/or have compromised health and wellbeing. Further work is required to pilot test the tool.


3D Numerical Study of the Electrokinetic Motion of a Microparticle Adsorbed at a Horizontal Oil/Water Interface in an Infinite Domain.
This work builds a three-dimensional (3D) simulation model and studies the electrokinetic velocity of a microparticle adsorbed at a horizontal oil/water interface in an infinite domain. The effects of the interface zeta potentials, the electric field, the oil dynamic viscosity, and the contact angle between the particle and the oil/water interface are investigated in detail. The results show that in an infinite oil/water interface system, both the negatively charged mobile oil/water interface and the negatively charged particle adsorbed to it move toward the positive electrode of the DC electric field, and the particle velocity increases along with the contact angle, the electric field strength, and the absolute values of negative zeta potential of both the particle and the oil/water interface. When the oil/water interface is positively charged with a relatively small zeta potential, the negatively charged microparticle also moves in the opposite direction of the electric field. The larger the oil dynamic viscosity, the smaller the electrokinetic velocity of the microparticle at the interface. Additionally, the numerical simulation results are compared with the reported experiment results under the same conditions, and they have good agreement.


Higher Body Mass Index Is Associated With Biochemical Changes in Knee Articular Cartilage After Marathon Running: A Quantitative T2-Relaxation MRI Study.
More than 30 million individuals participate in marathon running every year worldwide. As the popularity of marathon running continues to increase, it is essential for the purposes of injury prevention to understand the effects of marathon running on the knee cartilage. To investigate the immediate effects of marathon running on knee articular cartilage and to determine the relationship between body mass index and cartilage biochemical composition. Descriptive laboratory study. T2-relaxation magnetic resonance imaging (MRI) of knees in 18 nonprofessional marathoners (mean age, 35.6 ± 6.4 years) was performed before and after a full-length marathon. Three-dimensional models of the knee articular cartilage were reconstructed and divided into different regions of interest. The 3-dimensional models were then applied to corresponding T2-relaxation MRI maps to calculate T2 values in each region of interest. The mean values of the T2-relaxation times in each region of interest before and after the marathon were compared by use of the paired Student t test. The Pearson correlation coefficient between T2 change and runner body mass index (BMI) was calculated. Postmarathon T2-relaxation times were significantly higher than premarathon values for patellofemoral cartilage (32.6 ± 12.1 vs 34.1 ± 10.9 ms; P < .01) and medial tibial cartilage (35.6 ± 11.7 vs 34.6 ± 12.0 ms; P = .01). The greatest increase was observed in the anterior part of the medial tibial cartilage. No statistically significant changes were seen in the T2-relaxation times of the lateral tibial and femoral cartilage. Postmarathon T2-relaxation elevation in the anteromedial knee tibiofemoral joint cartilage strongly correlated with body weight (R = 0.6746; P = .03) and BMI (R = 0.6989; P = .001). Changes in T2-relaxation times did not correlate with marathon time, height, age, or sex in any regions of interest. Marathon running leads to immediate postmarathon elevated T2-relaxation values within knee articular cartilage, suggesting biochemical content alteration. Additionally, runners with higher BMI may have greater changes in cartilage biochemical composition after a marathon. Further studies should investigate whether these changes are sustained over time to determine the relationship between immediate biochemical changes in cartilage composition and cartilage degeneration. Runners with a higher BMI may carry a higher risk of anteromedial tibiofemoral cartilage degeneration compared with runners with lower BMI.


Highly Efficient Ionic Gating of Solid-State Nanosensors by the Reversible Interaction between Pillar[6]arene-AuNPs and Azobenzene.
By mimicking nature, various artificial nanofluidic platforms have been widely applied in a range of scientific fields. However, their low performance in terms of gating efficiency (<25) still hinders their practical applications. Herein, we present a highly efficient ionic gating nanosensor by fusing the merits of host-guest chemistry and Au nanoparticles (AuNPs). Based on this strategy, the pillar[6]arene (WP6)-functionalized AuNPs facilely regulated an azobenzene (AZO)-modified nanosensor with an excellent ion rectification ratio (∼22.2) and gating efficiency (∼89.5). More importantly, this gating nanosensor system also demonstrated promising stability and recyclability under conditions of alternative irradiation of visible and ultraviolet light. These excellent results would significantly help in expanding the utilization of artificial nanosensors for controllable drug delivery and biosensors.


Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma.
Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed. The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016), tumor size (P = 0.019), T status (P = 0.024), locoregional progression (P = 0.009) and EZH2 expression (P = 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (P = 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048), N0 (P = 0.005) and M0 (P = 0.018) stages as well as in CRT effective group (P = 0.022). Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.


Obstructive hypertrophic cardiomyopathy in Taiwanese adults.
The purpose of this study was to analyze the clinical profiles, echocardiographic findings, and mortality among adult Taiwanese patients with obstructive hypertrophic cardiomyopathy (HCM) at Chang Gung Memorial Hospital, a university-affiliated tertiary referral center in suburban Taipei. We reviewed the medical records of all adult (> 15 years of age) patients referred to our laboratory for echocardiographic examinations of cardiac diseases from May 1990 through December 1996. The diagnosis of obstructive HCM required an outflow gradient of above 10 mm Hg and the presence of asymmetric septal hypertrophy of the left ventricle. Follow-up information on was obtained from hospital records, questionnaires, interviews, or the National Death Certificate Registry. Of the 6.798 adults who underwent echocardiographic examinations during the study period 122 (1.79%) had obstructive HCM. The mean +/- standard deviation age of the patients was 62.2 +/- 12.6 years, and females predominated (n = 76, 62.3%). During the mean follow-up period of 3.2 years, the annual all-cause mortality rate was 4.7%. Most deaths were due to concurrent medical conditions. The annual cardiac mortality rate was 0.99%. Logistic regression analysis identified medication with calcium channel blockers as the only negative predictor (relative risk = 0.26, 95% confidence interval = 0.07-0.96) of all-cause mortality, and left atrial size as the only positive predictor (relative risk = 1.18, 95% confidence interval = 1.02-1.37) of cardiac mortality. Cox regression analysis confirmed the former association, but not the latter. Thus, in our institution, obstructive HCM had a low prevalence among adult patients referred for echocardiographic examination. These patients were elderly and often had other associated medical conditions. The high all-cause mortality rate was largely due to non-cardiac causes. These findings suggest that obstructive HCM tends to have a benign clinical course. Large atrial size could be an independent predictor of cardiac mortality, but this possibility requires further confirmation.


Siglecs and immune regulation.
Sialic acid-binding Ig-like lectins, or Siglecs, vary in their specificity for sialic acid-containing ligands and are mainly expressed by cells of the immune system. Many Siglecs are inhibitory receptors expressed in innate immune cells that regulate inflammation mediated by damage-associated and pathogen-associated molecular patterns (DAMPs and PAMPs). This family also includes molecules involved in adhesion and phagocytosis and receptors that can associate with the ITAM-containing DAP12 adaptor. Siglecs contribute to the inhibition of immune cells both by binding to cis ligands (expressed in the same cells) and by responding to pathogen-derived sialoglycoconjugates. They can help maintain tolerance in B lymphocytes, modulate the activation of conventional and plasmacytoid dendritic cells, and contribute to the regulation of T cell function both directly and indirectly. Siglecs modulate immune responses, influencing almost every cell in the immune system, and are of relevance both in health and disease.


Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells. Endothelial leukocyte adhesion molecule-1-mediated CD18 activation.
Adherence of neutrophils to endothelium is a key event in the sequence of inflammatory leukocyte responses. Double-color FACS analysis was used to determine the extent and kinetics of neutrophil adherence to rIL-1 beta-pretreated endothelial cells (EC). Neutrophils bound very avidly when the EC were prestimulated for 4 to 6 h with rIL-1 beta. Anti-ELAM-1 F(ab)2 fragments inhibited this adherence for more than 80%. On the other hand, anti-CD18 F(ab)2 fragments also inhibited the neutrophil adherence (40 to 50%). Combined use of anti-ELAM-1 and anti-CD18 F(ab)2 fragments completely prevented adherence. Neutrophils became activated as soon as they made contact with the rIL-1 beta-pretreated EC. First, neutrophils depleted of intracellular ATP showed a clearly decreased adherence completely dependent on ELAM-1-mediated binding, i.e., without additional effects of CD18 adhesion proteins. Thus, CD18 is activated during neutrophil adherence and then participates in the binding process. Secondly, the neutrophils responded with a transient rise in [Ca2+]i upon binding to rIL-1 beta-pretreated EC, which was demonstrated to be caused by endothelial cell-associated platelet-activating factor (PAF). However, the extent of neutrophil adherence to rIL-1 beta-pretreated EC was not affected by the use of the PAF-receptor antagonist WEB 2086, or removal of the EC-bound PAF. The only effect was a complete dependency of the neutrophil adherence on ELAM-1-mediated binding, although anti-CD18 mAb still induced 40 to 50% inhibition under these conditions. We therefore conclude that ELAM-1-mediated binding is the major mechanism for CD18 activation during neutrophil adherence to rIL-1 beta-pretreated EC.


[Phenotype of frailty: the influence of each item in determining frailty in community-dwelling elderly - The Fibra Study].
The phenotype of frailty is used to assess frailty among the elderly by examining the following items: weight loss; exhaustion; low level of physical activity; weakness; and slow gait speed. The aim of the study was to evaluate the contribution of each item to determine the frailty syndrome among elderly Brazilians. The analysis was done using Multinomial Logistic Regression. The total sample of 5532 randomly selected elderly people in many cities in Brazil between December 2008 and September 2009 was assessed using the phenotype of frailty. The most frequent items were level of physical activity, followed by muscular weakness and slow gait speed. Items that were more likely to develop frailty, when positive, were slow gait speed (OR = 10.50, 95%CI 8.55 - 12.90, p <0.001) and muscular weakness (OR = 7.31, 95%CI 6,02 - 8,86, p <0.001). The final model with five items explained 99.6% of frailty in the sample. These results suggested that the level of physical activity, weakness and slow gait speed were the items that most influence the determination of frailty, however the application of all items of the phenotype of frailty is the best way to assess frailty.


Transference and Countertransference Dynamics in a Multifamily Group for Transgender Adolescents.
This article is an account of a pioneering multifamily group for transgender adolescents. Meetings were conducted in a Sexual Identity Consultation Service in a Child and Adolescent Psychiatry Department in Paris. In addition to enabling both teenagers and their parents to escape a certain form of isolation, this novel mental health care setting also reinforced the ability of participants to free associate and to cathect substitute objects. The author highlights specific characteristics of transference movements and countertransference reactions of the therapists in this framework. An additional goal is to promote these innovative groups and to recommend similar groups for transgender adolescents and their parents.


Calcium Mobilization Systems During Neurogenesis.
Neuroepithelial cells have Ca(2+) mobilization systems that are activated by acetylcholine via muscarinic receptors and by extracellular ATP via P(2U) purinoceptors. The Ca(2+) mobilization occurs during neurogenesis and diminishes in parallel with the declining of mitotic activities of the neuroepithelial cells. Capacitative Ca(2+) influx also occurs with the Ca(2+) mobilization.


Ground Reaction Forces of the Lead and Trail Limbs when Stepping Over an Obstacle.
Precise force generation and absorption during stepping over different obstacles need to be quantified for task accomplishment. This study aimed to quantify how the lead limb (LL) and trail limb (TL) generate and absorb forces while stepping over obstacle of various heights. Thirteen healthy young women participated in the study. Force data were collected from 2 force plates when participants stepped over obstacles. Two limbs (right LL and left TL) and 4 conditions of stepping (no obstacle, stepping over 5 cm, 20 cm, and 30 cm obstacle heights) were tested for main effect and interaction effect by 2-way ANOVA. Paired t-test and 1-way repeated-measure ANOVA were used to compare differences of variables between limbs and among stepping conditions, respectively. The main effects on the limb were found in first peak vertical force, minimum vertical force, propulsive peak force, and propulsive impulse. Significant main effects of condition were found in time to minimum force, time to the second peak force, time to propulsive peak force, first peak vertical force, braking peak force, propulsive peak force, vertical impulse, braking impulse, and propulsive impulse. Interaction effects of limb and condition were found in first peak vertical force, propulsive peak force, braking impulse, and propulsive impulse. Adaptations of force generation in the LL and TL were found to involve adaptability to altered external environment during stepping in healthy young adults.


[Varicocele in adolescents. 67 cases].
We examined 67 adolescents aged 11 to 14 years referred for left varicocele. Atrophy of the testes was present in 38 (75%). Several techniques, including laparoscopic surgery were used. The best method appears to be ligation of the spermatic veins via an inguinal approach without touching the artery if possible. Recurrence (5%) is always caused by missing a vein. Growth of the testis occurred in all cases after treatment of the varicocele.


Prospective spatial-temporal clusters of COVID-19 in local communities: case study of Kansas City, Missouri, United States.
Kansas City, Missouri, became one of the major United States hotspots for COVID-19 due to an increase in the rate of positive COVID-19 test results. Despite the large numbers of positive cases in Kansas City, MO, the spatial-temporal analysis of data has been less investigated. However, it is critical to detect emerging clusters of COVID-19 and enforce control and preventive policies within those clusters. We conducted a prospective Poisson spatial-temporal analysis of Kansas City, MO data to detect significant space-time clusters of COVID-19 positive cases at the zip code level in Kansas City, MO. The analysis focused on daily infected cases in four equal periods of 3 months. We detected temporal patterns of emerging and re-emerging space-time clusters between March 2020 and February 2021. Three statistically significant clusters emerged in the first period, mainly concentrated in downtown. It increased to seven clusters in the second period, spreading across a broader region in downtown and north of Kansas City. In the third period, nine clusters covered large areas of north and downtown Kansas City, MO. Ten clusters were present in the last period, further extending the infection along the State Line Road. The statistical results were communicated with local health officials and provided the necessary guidance for decision-making and allocating resources (e.g., vaccines and testing sites). As more data become available, statistical clustering can be used as a COVID-19 surveillance tool to measure the effects of vaccination.


Expression of oestrogen receptor alpha and beta mRNA in corpus luteum of human subjects.
To investigate the role of oestrogen receptor beta (ERbeta) in the function of human ovarian corpus luteum, the levels of luteal ERalpha and ERbeta mRNA were determined using competitive reverse transcription-polymerase chain reaction-Southern blot analysis. The expression of ERalpha and ERbeta mRNA was detected in all luteal samples analysed. Luteal ERalpha and ERbeta mRNA levels were significantly lower (P<0.01 and P<0.05 respectively) at the late secretory phase than those at the early and mid-secretory phases of the endometrium. The ratio of ERalpha to ERbeta mRNA levels showed no change during the secretory phase of the endometrium. This study demonstrates that ERbeta is co-expressed with ERalpha in human corpus luteum and is likely to play a biological role in the regulation of steroidal action of the corpus luteum with ERalpha.


Mucociliary and cough clearance as a biomarker for therapeutic development.
A workshop/symposium on "Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development" was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed to improve clearance of airway secretions from the lungs. The utility of MCC/CC as a biomarker for disease progression and therapeutic intervention is gaining increased recognition as a valuable tool in the clinical research community. A number of investigators currently active in using MCC/CC for diagnostic or therapeutic evaluation presented details of their methodologies. Attendees participating in the workshop discussions included those interested in the physiology of MCC/CC, some of who use in vitro or animal methods for its study, pharmaceutical companies developing muco-active therapies, and many who were interested in establishing the methods in their own clinical laboratory. This review article summarizes the presentations for the in vivo human MCC/CC methods and the discussions both at and subsequent to the workshop between the authors to move forward on a number of questions raised at the workshop.


An evaluation of the performance of an automated procedure for comparative modelling of protein tertiary structure.
A 3-D model of a protein can be constructed from its amino acid sequence and the 3-D structures of one or more homologues by annealing three sets of fragments: the structurally conserved regions, structurally variable regions and the side chains. The method encoded in the computer program COMPOSER was assessed by generating 3-D models of eight proteins whose crystal structures are already known and for which 3-D structures of homologues are available. In the structurally conserved regions, differences between modelled and X-ray structures are smaller than the differences between the X-ray structures of the modelled protein and the homologues used to build the model. When several homologues are used, the contributions of the known structures are weighted, preferably by the square of sequence similarity; this is especially important when the similarities of the homologues to the modelled structure differ greatly. The 'collar' extension approach, in which a similar region of different length in a homologue is used to extend the framework, can result in a more accurate model. If known homologues comprise more than one related group of proteins and they are both distantly related to the unknown, then alignment of the sequence to be modelled with each group of homologues facilitates identification of structurally conserved regions of the unknown and leads to an improved model. Models have root mean square differences (r.m.s.d.s) with the structures defined by X-ray analysis of between 0.73 and 1.56 A for all C alpha atoms, for seven the eight models. For the model of mucor pepsin, where the closest homologue has 33% sequence identity and 20% of the residues are in structurally variable regions, the r.m.s.d. for the framework region is 1.71 A and the r.m.s.d. for all C alpha atoms is 3.47 A.


Human plasma copper proteins speciation by size exclusion chromatography coupled to inductively coupled plasma mass spectrometry. Solutions for columns calibration by sulfur detection.
Among the hyphenated techniques used to probe and identify metalloproteins, size exclusion chromatography coupled to inductively coupled plasma mass spectrometry (SEC-ICP-MS) has shown to have a central place. However, the calibration of SEC columns reveals to be tedious and always involves UV detection prior to ICP-MS. The presence of sulfur in 98% of proteins allows their detection by quadrupole ICP-MS, despite the isobaric interference ((16)O(16)O) on S, by monitoring (32)S(16)O at mass to charge ratio (m/z) 48. The formation of SO occurs spontaneously in the argon plasma but can be optimized by the introduction of oxygen gas into a reaction cell (RC) to achieve nM levels. In this article, sulfur detection was discussed upon instrumental conditions and S detection was then optimized by applying O(2) as a reaction gas. SO formation was used to calibrate SEC columns without UV detection. This simple SEC-ICP-MS method was used for plasma copper proteins in plasma healthy subjects (HS) and an untreated Wilson disease (WD) patient. Copper proteins identified in healthy subjects were transcuprein, ceruloplasmin (Cp) and albumin. The method led to results in good agreement with other methods of determination. Copper bound to Cp in the WD patient was lowered with regard to the HS, and the exchangeable Cu was highly increased.


Reversed-phase planar chromatography of some enantiomeric amino acids and oxazolidinones.
The resolution of two enantiomeric amino acids and four structurally related oxazolidinones was evaluated by reversed-phase planar chromatography using both home-made microcrystalline cellulose triacetate (MCTA) layers and mobile phase additivies, such as beta-cyclodextrins (beta-Cy), modified alpha, beta, gamma cyclodextrins and bovine serum albumin (BSA), on commercially available RP-18W/F254 and SilC18-50/UV254 plates. All the enantiomers were partially or baseline resolved by at least one of the chiral phases tested. Densitograms of optical antipodes and their mixtures were measured on MCTA layers developed with hydroalcoholic solvents.


Zinc oxide nanoparticles inhibit expression of manganese superoxide dismutase via amplification of oxidative stress, in murine photoreceptor cells.
As a parenchymal cell, the photoreceptor is more susceptible to alterations in outer micro-environmental conditions than other cells. In the present study, we aimed to investigate inhibitory effects of zinc oxide (ZnO) nanoparticles on expression of manganese superoxide dismutase (MnSOD) in murine photoreceptor-derived cells. We investigated effects of ZnO nanoparticles on murine photoreceptor cell viability and on expression and activity of MnSOD using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, immunofluorescence analysis, flow cytometry, quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). ZnO nanoparticles were found to have higher cytotoxic effects in concentration- and time-dependent manners, to elevate intracellular levels of hydrogen peroxide and hydroxyl radicals, and thus to induce overproduction of reactive oxygen species (ROS) and collapse of mitochondrial membrane potential, leading to cell damage. Moreover, ZnO nanoparticles also significantly reduced expression of MnSOD at both the mRNA and protein levels, reduced its activity, and further aggravated oxidative stress-mediated cell damage. Overall, ZnO nanoparticle-induced cytotoxicity was associated with elevated levels of oxidative stress due to overproduction of ROS and reduced expression and activity of MnSOD.


Neurotoxic activity and ultrastructural changes in muscles caused by the brown widow spider Latrodectus geometricus venom.
Brown widow spider (Latrodectus geometricus) venom (BrWSV) produces few local lesions and intense systemic reactions such as cramps, harsh muscle pains, nausea, vomiting and hypertension. Approximately 16 protein bands under reducing conditions and approximately 14 bands under non-reducing conditions on a 12.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis were observed. Neurotoxic clinical manifestations were confirmed in vivo, while proteolytic activity was demonstrated on gelatine film. Severe ultrastructural damages in mice skeletal muscles were observed at 3, 6, 12 and 24 h postinjection with at total of 45 microg of venom protein. Infiltration of eosinophils and ruptures of the cellular membranes were observed in the muscles along with swelling of the nuclear cover and interruption of the collagen periodicity. Altered mitochondrias and autophage vacuoles, nuclear indentation and mitochondria without cristae, slight increment of intermyofibrillar and subsarcolemic spaces and myelinic figures formation were also observed. In the capillary, endothelial membrane unfolding into the lumen was noticed; along with myelinic figures compatible with a toxic myopathy. Swollen sarcotubular systems with lysis of membrane, intense mitochondria autophagia and areas without pinocytic vesicles were observed. Swollen mitochondria surrounded by necrotic areas, myofibrillar disorganization and big vacuolas of the sarcotubular system, degenerated mitochondrium with formation of myelinic figure was seen. Glycogenosomes with small particulate, muscle type glycogen was noticed. Autophagic vacuole (autophagolysosomes) and necrotic areas were also noticed. These damages may be due to interactive effects of the multifactorial action of venom components. However, Latrodectus geometricus venom molecules may also be utilized as neuro therapeutic tools, as they affect neuronal activities with high affinity and selectivity. To our knowledge, the present study is the first ultrastructural report in the literature of muscle injuries and neurological and proteolytic activities caused by BrWSV.


Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene.
With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34(+) progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell growth by reducing levels of reactive oxygen species (ROS) generated in response to cytokines. Forced PRDX2 expression inhibited c-Myc-induced leukemogenesis in vivo on BM transplantation in mice. Taken together, epigenome-wide analyses of H3Ac in AML led to the identification of PRDX2 as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML.


Ergosterol treatment leads to the expression of a specific set of defence-related genes in tobacco.
Ergosterol is the main sterol of most fungi. Production of reactive oxygen species after the treatment of tobacco and tomato cells by nano-molar concentrations of ergosterol was previously observed as well as the activation of some stress activated mitogen-activated protein kinases on alfalfa cells. In this paper, the expression of some defence-related genes after the ergosterol treatment of tobacco Nicotiana tabacum plants is reported. The gene expression of pathogenesis related proteins of families PR1, PR3, PR5 and proteinase inhibitors of class I and II together with enzymes participating in the defence response, such as phenylalanine-ammonia lyase and sesquiterpene cyclase, were monitored by RT-qPCR. In addition, the concentrations of salicylic acid, an important signalling molecule, increased in time due to the enzyme activation. On the other hand, ergosterol did not provoke tissue necrosis and the possible cross-talk between the signalling pathways of salicylate and jasmonate was observed. Collected data shows that ergosterol is able to activate the expression of a number of defence genes and could increase resistance against pathogens.


Structure-Revealing Low-Light Image Enhancement Via Robust Retinex Model.
Low-light image enhancement methods based on classic Retinex model attempt to manipulate the estimated illumination and to project it back to the corresponding reflectance. However, the model does not consider the noise, which inevitably exists in images captured in low-light conditions. In this paper, we propose the robust Retinex model, which additionally considers a noise map compared with the conventional Retinex model, to improve the performance of enhancing low-light images accompanied by intensive noise. Based on the robust Retinex model, we present an optimization function that includes novel regularization terms for the illumination and reflectance. Specifically, we use norm to constrain the piece-wise smoothness of the illumination, adopt a fidelity term for gradients of the reflectance to reveal the structure details in low-light images, and make the first attempt to estimate a noise map out of the robust Retinex model. To effectively solve the optimization problem, we provide an augmented Lagrange multiplier based alternating direction minimization algorithm without logarithmic transformation. Experimental results demonstrate the effectiveness of the proposed method in low-light image enhancement. In addition, the proposed method can be generalized to handle a series of similar problems, such as the image enhancement for underwater or remote sensing and in hazy or dusty conditions.


Improving perception to make distant connections closer.
One of the challenges for perceptually grounded accounts of high-level cognition is to explain how people make connections and draw inferences between situations that superficially have little in common. Evidence suggests that people draw these connections even without having explicit, verbalizable knowledge of their bases. Instead, the connections are based on sub-symbolic representations that are grounded in perception, action, and space. One reason why people are able to spontaneously see relations between situations that initially appear to be unrelated is that their eventual perceptions are not restricted to initial appearances. Training and strategic deployment allow our perceptual processes to deliver outputs that would have otherwise required abstract or formal reasoning. Even without people having any privileged access to the internal operations of perceptual modules, these modules can be systematically altered so as to better serve our high-level reasoning needs. Moreover, perceptually based processes can be altered in a number of ways to closely approximate formally sanctioned computations. To be concrete about mechanisms of perceptual change, we present 21 illustrations of ways in which we alter, adjust, and augment our perceptual systems with the intention of having them better satisfy our needs.


Multiple Anti-Kasha Emissions in Transition-Metal Complexes.
In this Letter, we present first-principles evidence that several higher-lying excited states are responsible for the emission spectrum of [M(CO)4(bpy)] (M = Cr, Mo, W and bpy = 2,2'-bipyrimidine) complexes. These results highlight the violation of Kasha's rule, which states that after irradiation, molecules emit light with appreciable yield only from their lowest energy excited state. Furthermore, in [W(CO)4(bpy)] and [Mo(CO)4(bpy)], the breaking of Kasha's rule is two-fold because at least two different excited states besides T1 are involved in emission. To our knowledge, these are the first transition-metal complexes unambiguously demonstrated to display simultaneous equilibrated and nonequilibrated anti-Kasha emissions. This work also highlights the complexity of the emissive processes of tetracarbonyl-diimine transition-metal complexes, which are controlled via a subtle interplay of electronic and geometrical effects along the excited-state deactivation dynamics.


Motivational interviewing for adherence problems in cystic fibrosis; evaluation of training healthcare professionals.
Motivational interviewing (MI) offers effective strategies for enhancing behaviour change and is particularly useful for patients who exhibit poor adherence. This study evaluated MI training for cystic fibrosis (CF) teams, which comprised of one 4-hour workshop on MI principles, followed 6 months later by another on applying MI during brief consultations. Health professionals (N = 60) from 7 teams completed questionnaires on learning outcomes 6 months after the first workshop, but before the second. Eleven participated in telephone-interview, 3 months after the second workshop. Quantitative analysis showed all participants used MI with a patient at least once after the first workshop and felt the approach was potentially helpful. Although self-appraisal of skill and confidence in MI was 'moderate', all felt confident in their ability to develop their skills and almost all intended to use MI in the future. Qualitative analysis confirmed the positive experiences of training and of using MI in practice, particularly in relationship building. However MI was utilised depending on team support and workload pressures. This study showed that initial MI training with CF team-members resulted in increased knowledge and confidence about acquiring and applying MI techniques. However, this was balanced with consideration of barriers to application, further training needs and ongoing team-based support.


Speech understanding in quiet and in noise with the CIS speech coding strategy (MED-EL Combi-40) compared to the multipeak and spectral peak strategies (nucleus).
This study compares sentence understanding in quiet and in noise with 3 different speech coding strategies for cochlear implants. The results show that the spectral-peak (SPEAK) and continuous-interleaved-sampling (CIS) coding strategies, based on spectral signal analysis, allow for better speech understanding in quiet as well as in noise, than the multipeak (MPEAK) coding strategy, which relys on speech feature extraction. In the intrasubject comparison of the MPEAK and SPEAK strategies, the SPEAK coding strategy provided a considerable improvement in quiet and in noise for the majority of patients using the Nucleus 22 Mini-implant. In the intersubject comparisons, the mean results in noise with the CIS strategy were superior to both the MPEAK and the SPEAK strategies. The difference was greatest for the most difficult tests in noise. Understanding in noise was least reduced for the CIS strategy. Understanding in quiet was not significantly different between the CIS and the SPEAK strategies; both strategies were significantly better than the MPEAK strategy in quiet. These results are still preliminary, due to the relatively small number of patients and the great inherent intersubject variability of results.


Clinical intracytoplasmic sperm injection (ICSI) results from Royal North Shore Hospital.
The technique of intracytoplasmic sperm injection (ICSI) was first introduced to the Royal North Shore Hospital in April 1993 as part of a controlled study of 100 patient cycles in which sibling oocytes were inseminated by either subzonal insemination (SUZI) or ICSI. This trial showed direct sperm injection to be superior in terms of fertilization. In that study, 58 embryo transfers of 101 ICSI-derived embryos resulted in 10 pregnancies. No miscarriages have occurred and a total of 10 fetal hearts (9.8% per embryo transferred) were detected on ultrasound. There have been 10 deliveries of 10 babies. Since the beginning of 1994, intracytoplasmic injection has been used exclusively for patients requiring micromanipulation to achieve fertilization. There have been 200 patient cycles with 1650 oocytes collected (8.8 oocytes per cycle). Of these oocytes, 1548 were mature (94%) and were subjected to ICSI, and normal fertilization occurred in 874 (56%) of the injected oocytes. The number of oocytes which cleaved and were suitable for fresh transfer or cryopreservation was 818 (94%). There have been 153 fresh embryo transfers of 326 embryos. Twenty-six pregnancies (17% per embryo transfer) have resulted, 22 of which proceeded to ultrasound examination in which 23 fetal hearts were detected (7% per embryo transferred). Three miscarriages have occurred, leaving 19 ongoing pregnancies. There have been 127 cryopreservation procedures involving 492 embryos. To date, there have been 47 embryo thaw cycles, and 93 of the 115 (81%) thawed embryos survived and were transferred. These 47 embryo transfers resulted in 10 pregnancies (21% per embryo transfer), one of which one has miscarried.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of chemosensitivity for patients with acute myeloid leukemia, according to expression levels of 28 genes selected by genome-wide complementary DNA microarray analysis.
To identify genes involved in the sensitivity of acute myeloid leukemia (AML) cells to chemotherapy, we monitored gene-expression profiles of cancer cells from 76 AML patients using a cDNA microarray consisting of 23,040 genes. We identified 63 genes that were commonly overexpressed and 372 genes suppressed in AML. Because these genes represent key molecules for disclosing the molecular mechanisms of AML, they may be potential targets for drug development. We also found 28 that revealed different expression levels between good and poor responders to chemotherapy and appeared to be associated with chemosensitivity. On that basis, we developed a "Drug Response Scoring" system that was correlated well with individual sensitivity to an anticancer drug regimen. Among the 44 cases with positive drug-response scores by our definition, 40 achieved complete remission after treatment, whereas the only 3 of the 20 cases with negative scores responded well to the treatment. An ability to predict chemosensitivity should eventually lead to achievement of our goal of "personalized therapy."


New Furanocembranoids from Briareum violaceum.
Three new furanocembranoids-briaviodiol F (1) and briaviotriols A (2) and B (3)-along with a known analogue, briaviodiol A (4), were obtained from a cultured-type octocoral Briareum violaceum. The structures of cembranoids 1⁻3 were elucidated by using spectroscopic methods. In vitro study demonstrated that compounds 2 and 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW 264.7, a macrophage cell line that originated from a mouse monocyte macrophage, stimulated with lipopolysaccharides.


The role of R576Q polymorphism of interleukin-4 receptor alpha gene in atopy: results of a family-based study design.
There is strong evidence that the R576 allele of interleukin-4 receptor alpha gene (IL-4R) might predispose to atopy. To test this hypothesis, we examined the association between the R576Q polymorphism and atopy in a Polish population using the family-based study design. 44 atopic patients (age range from 11 to 34 years) with pollen and house dust mite allergy or/and mild asthma together with both parents were studied. The R576Q polymorphism of the IL-4R gene was genotyped in each patient and both parents, respectively, using the PCR-based protocol. The results were analyzed by the transmission disequilibrium test (TDT). The total IgE serum level, allergen-specific IgE to the common aeroallergens, IL-4, and sIL-4Ralpha were assessed in each patient and both parents. In the TDT test the R576 and Q576 alleles were transmitted from the heterozygous parents to the affected offspring 20 and 15 times, respectively (McNemar test: p = 0.19). The results of the transmission disequilibrium test did not reach statistical significance. Thus, the R576 allele might contribute to the pathogenesis of allergic diseases in patients with high total IgE serum level (p < 0.05). A larger study group has to be studied to prove the observed linkage and association.


Interface contact profiles of a novel locking plate and its effect on fracture healing in goat.
To evaluate the interface characteristics of the new-designed locking plate (LP) and limited contact-dynamic compression plate (LC-DCP) and compare the fracture healing between LP and LC-DCP in a goat tibia fracture model. Eight-hole LP and LC-DCP were applied to fix fresh goat tibiae in a reproducible manner. The average pressure, force and interface contact area were calculated using Fuji prescale pressure sensitive film interposed among the plate and the bone and image analysis system. Eight-hole LP and LC-DCP were applied to each tibia in a goat tibia fracture model. The fracture healing was evaluated by X-ray photography at postoperative 8 weeks. The goats were sacrificed at postoperative 12 weeks. Three-point bending test was conducted in the tibiae. The interface contact of LP system was smaller than that of LC-DCP (P < 0.05), while interface contact force of LP system was higher than that of LC-DCP (P < 0.05). Radiographs revealed that the fracture line disappeared in the LP group, while the fracture line was visible in DCP group at postoperative 8 weeks. At postoperative 12 weeks, the bending strength and bending load of fractured tibia were higher in LP group than in DCP group, respectively. The new-designed locking plate can significantly decrease the contact area on the bone interface, which further provides better fracture healing than conventional plates.


Inductive impedance transducer for recording displacements of ferromagnetic and nonferromagnetic conductive objects.
The paper describes an inductive magnetic transducer for on-line recording of translations and vibrations. The transducer consists of an iron cored sensor coil and simple accompanying circuitry. The main features which are peculiar to the present transducer are (a) facility for linearizing the voltage versus displacement characteristic for certain regions of distances, (b) ability to measure vibrations and translations of both ferromagnetic objects and nonferromagnetic conductive objects, (c) relative simplicity of circuitry, and (d) the fact that only passive components are used for the transducer and an output voltage enhancement is attained by the employment of resonance. The paper is introduced by a comprehensive review of various types of magnetic transducers.


Candida mediastinitis and septic shock following occult esophageal perforation in a patient with posttraumatic quadriplegia.
Unexplained septic shock was ultimately shown to be caused by Candida mediastinitis after perforation of the cervical esophagus by a dislodged cervical methylmethacrylate construct in a 25-year-old patient with traumatic quadriplegia. Communication between the prevertebral abscess and pleural space further led to the formation of a esophageal-pleural-cervical fistula. Despite antibiotics, surgical removal of the construct, and drainage of the esophagus and mediastinum, the patient died from refractory shock and respiratory failure.


Loci Encoding Compounds Potentially Active against Drug-Resistant Pathogens amidst a Decreasing Pool of Novel Antibiotics.
Since the discovery of penicillin, microbes have been a source of antibiotics that inhibit the growth of pathogens. However, with the evolution of multidrug-resistant (MDR) strains, it remains unclear if there is an abundant or limited supply of natural products to be discovered that are effective against MDR isolates. To identify strains that are antagonistic to pathogens, we examined a set of 471 globally derived environmental Pseudomonas strains (env-Ps) for activity against a panel of 65 pathogens including Achromobacter spp., Burkholderia spp., Pseudomonas aeruginosa, and Stenotrophomonas spp. isolated from the lungs of cystic fibrosis (CF) patients. From more than 30,000 competitive interactions, 1,530 individual inhibitory events were observed. While strains from water habitats were not proportionate in antagonistic activity, MDR CF-derived pathogens (CF-Ps) were less susceptible to inhibition by env-Ps, suggesting that fewer natural products are effective against MDR strains. These results advocate for a directed strategy to identify unique drugs. To facilitate discovery of antibiotics against the most resistant pathogens, we developed a workflow in which phylogenetic and antagonistic data were merged to identify strains that inhibit MDR CF-Ps and subjected those env-Ps to transposon mutagenesis. Six different biosynthetic gene clusters (BGCs) were identified from four strains whose products inhibited pathogens including carbapenem-resistant P. aeruginosa BGCs were rare in databases, suggesting the production of novel antibiotics. This strategy can be utilized to facilitate the discovery of needed antibiotics that are potentially active against the most drug-resistant pathogens.IMPORTANCE Carbapenem-resistant P. aeruginosa is difficult to treat and has been deemed by the World Health Organization as a priority one pathogen for which antibiotics are most urgently needed. Although metagenomics and bioinformatic studies suggest that natural bacteria remain a source of novel compounds, the identification of genes and their products specific to activity against MDR pathogens remains problematic. Here, we examine water-derived pseudomonads and identify gene clusters whose compounds inhibit CF-derived MDR pathogens, including carbapenem-resistant P. aeruginosa.


Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled.
Abnormal retinal neovascularization associated with various retinopathies can result in irreversible vision loss. Although the mechanisms involved in this occurrence is unclear, increasing evidence suggests that aberrant Wnt signaling participates in the pathogenesis of abnormal neovascularization. Because Wnt signaling upregulation can be induced by oxidative stress through the activation of disheveled (DVL), a key molecule in the Wnt signaling pathway, we investigated whether oxidative stress can activate Wnt signaling and induce angiogenic phenotypes in human retinal microvascular endothelial cells (HRMECs). We found that increased Wnt signaling activity, as well as enhanced angiogenic phenotypes, such as tube formation and cell migration, were detected in the hydrogen peroxide-treated HRMECs. Moreover, these effects were effectively suppressed by a small-molecule Wnt inhibitor targeting the PDZ domain of DVL. Therefore, we propose that targeting abnormal Wnt signaling at the DVL level with a small-molecule inhibitor may represent a novel approach in retinal neovascularization treatment and prevention.


Desorption behaviors of BDE-28 and BDE-47 from natural soils with different organic carbon contents.
Desorption kinetic and isothermal characteristics of BDE-28 and BDE-47 were investigated using natural soils with different organic carbon fractions. The results indicated that a two-compartment first-order model with dominant contribution of slow desorption could adequately describe the released kinetics of studied PBDEs. Desorption isotherms of different samples could be fitted well by linear distribution model or nonlinear Freundlich model. Moreover, most desorption procedures roughly exhibited hysteresis with respect to preceding sorption ones. At the statistically significant level of 0.05 or 0.1, total organic carbon content (f(OC)) exhibited significant correlations with the fitted parameters by the isothermal models. The correlations of f(OC) and SOM fractions (e.g., fulvic acid and humin) with the single point desorption coefficients at lower aqueous concentrations of studied PBDEs were significant; while at higher aqueous concentrations, the relationships were less significant or insignificant. Our findings may facilitate a comprehensive understanding on behaviors of PBDEs in soil systems.


The origin of the conductivity maximum in molten salts. II. SnCl2 and HgBr2.
The phenomenon of electrical conductivity maxima of molten salts versus temperature during orthobaric (closed-vessel) conditions is further examined via ab initio simulations. Previously, in a study of molten BiCl3, a new theory was offered in which the conductivity falloff at high temperatures is due not to traditional ion association, but to a rise in the activation energy for atomic ions hopping from counterion to counterion. Here this theory is further tested on two more inorganic melts which exhibit conductivity maxima: another high-conducting melt (SnCl2, σmax = 2.81 Ω(-1) cm(-1)) and a low-conducting one (HgBr2, σmax = 4.06 × 10(-4) Ω(-1) cm(-1)). First, ab initio molecular dynamics simulations were performed and again appear successful in reproducing the maxima for both these liquids. Second, analysis of the simulated liquid structure (radial distributions, species concentrations) was performed. In the HgBr2 case, a very molecular liquid like water, a clear Grotthuss chain of bromide transfers was observed in simulation when seeding the system with a HgBr(+) cation and HgBr3 (-) anion. The first conclusion is that the hopping mechanism offered for molten BiCl3 is simply the Grotthuss mechanism for conduction, applicable not just to H(+) ions, but also to halide ions in post-transition-metal halide melts. Second, it is conjectured that the conductivity maximum is due to rising activation energy in network-covalent (halide-bridging) melts (BiCl3, SnCl2, PbCl2), but possibly a falling Arrhenius prefactor (collision frequency) for molecular melts (HgBr2).


Ozonation followed by coagulation/flocculation and flotation as post-treatment of the effluent from an anaerobic baffled reactor treating domestic sewage.
This paper reports on the use of ozonation and dissolved air flotation as a post-treatment of the effluent from an anaerobic baffled reactor treating domestic sewage. After preliminary essays, the present experiment was performed fixing coagulant doses and, to all of them, some ozone doses were investigated. Later, the pH value and the ozone dose which provided the best removal efficiencies of all the parameters involved were tested, changing the coagulant dose and varying, for each of them, two ozone doses: the zero one and the optimum. Considering the best conditions of coagulation/flotation (ferric chloride dose of 65 mg.L-1 and pH around 5.5), the ozone dose application of 6 mg.L-1 led to a significant level in the removal efficiency of COD (80.4%), BOD (79.0%), total phosphate (93.4%), apparent color (91.9%) and turbidity (97.0%), demonstrating that the system seems to be efficient and capable of promoting a high degree of sewage post-treatment, reducing the coagulant dose until 30%, with a consequent reduction in the sludge generation.


Induction of indoleacetic Acid synthetases in tobacco pith explants.
Formation of indoleacetic acid synthetases in tobacco pith explants was determined by following the growth of tissue cultures under conditions of indole-3-acetic acid (IAA) deprivation and by measuring the enzymatic conversion of tryptophan to IAA in the cultures. The pith explants obtained from the parent plant (Nicotiana glauca) and from basal regions of the tumor-prone hybrid (N. glauca x N. langsdorffii) both show a requirement for exogenous IAA for growth initiation in culture. The parent pith requires the constant presence of added IAA for continued growth, but hybrid pith, after initial treatment with IAA, will grow without further additions. IAA synthetases are detected in the cell homogenates of hybrid pith explants cultured with either continuous or initial IAA addition. These observations indicate that IAA may induce its own production. In contrast, IAA synthetases are not found in the parent pith under comparable culture conditions. Besides IAA, nonhormonal compounds such as indole and tryptophan are also capable of stimulating growth of hybrid pith, possibly through the induction of IAA synthetases needed for IAA formation. Indole and tryptophan are, however, inactive in growth promotion of the parent pith. These results suggest that the genomic expression of IAA synthetase formation is more stringently controlled in N. glauca than in the tumorprone hybrid.


The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons.
The dorsal root ganglia (DRG) and trigeminal ganglia (TG) are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.


Rapid isolation of mesophyll cells from leaves of soybean for photosynthetic studies.
Mesophyll cells were rapidly isolated from soybean (Glycine max [L.]) leaves using a combined Macerase enzyme-stirring technique. About 50% to 70% of the leaf cells on a chlorophyll basis from 3 grams of leaves could be isolated in 15 minutes. The cells obtained by this method were capable of high rates of photosynthesis even after storage in the dark for periods of up to 9 hours. The CO(2)-saturated rate of photosynthesis increased from 5 mum CO(2)/mg Chl.hour at 5 C to 170 mum CO(2)/mg Chl.hour at 40 C. At atmospheric CO(2) concentration, the rate varied from 5 to 55 mum CO(2)/mg Chl.hour over this temperature range. The reduced temperature response of photosynthesis at low CO(2) concentration was due to an increased Km(CO(2)) of the cells with increasing temperature. The products of photosynthesis in the isolated cells were similar to the products of leaf photosynthesis.


Establishment of an in vitro transport assay that reveals mechanistic differences in cytosolic events controlling cholera toxin and T-cell receptor α retro-translocation.
Following retrograde trafficking to the endoplasmic reticulum (ER), cholera toxin A1 (CTA1) subunit hijacks ER-associated degradation (ERAD) machinery and retro-translocates into the cytosol to induce toxicity. We previously established a cell-based in vivo assay to identify ER components that regulate this process. However, elucidating cytosolic events that govern CTA1 retro-translocation using this assay is difficult as manipulating cytosolic factors often perturbs toxin retrograde transport to the ER. To circumvent this problem, we developed an in vitro assay in semi-permeabilized cells that directly monitors CTA1 release from the ER into the cytosol. We demonstrate CTA1 is released into the cytosol as a folded molecule in a p97- and proteasome-independent manner. Release nonetheless involves a GTP-dependent reaction. Upon extending this assay to the canonical ERAD substrate T-cell receptor α (TCRα), we found the receptor is unfolded when released into the cytosol and degraded by membrane-associated proteasome. In this reaction, p97 initially extracts TCRα from the ER membrane, followed by TCRα discharge into the cytosol that requires additional energy-dependent cytosolic activities. Our results reveal mechanistic insights into cytosolic events controlling CTA1 and TCRα retro-translocation, and provide a reliable tool to further probe this process.


Differences in Circulating microRNAs between Grazing and Grain-Fed Wagyu Cattle Are Associated with Altered Expression of Intramuscular microRNA, the Potential Target PTEN, and Lipogenic Genes.
We aimed to understand the roles of miRNAs in the muscle tissue maturation and those of circulating microRNAs (c-miRNAs) in beef production of Japanese Black (JB) cattle (Wagyu), a breed with genetically background of superior intermuscular fat depot, by comparing different feeding conditions (indoor grain-feeding vs. grazing on pasture). The cattle at 18 months old were assigned to pasture feeding or conventional indoor grain feeding conditions for 5 months. Microarray analysis of c-miRNAs from the plasma extracellular vesicles led to the detection of a total of 202 bovine miRNAs in the plasma, including 15 miRNAs that differed between the feeding conditions. Validation of the microarray results by qPCR showed that the circulating miR-10b level in the grazing cattle was upregulated compared to that of the grain-fed cattle. In contrast, the levels of miR-17-5p, miR-19b, miR-29b, miR-30b-5p, miR-98, miR-142-5p, miR-301a, miR-374b, miR-425-5p, and miR-652 were lower in the grazing cattle than in the grain-fed cattle. Bioinformatic analysis indicated that the predicted target genes of those c-miRNAs were enriched in gene ontology terms associated with blood vessel morphogenesis, plasma membrane, focal adhesion, endocytosis, collagen, ECM-receptor interaction, and phosphorylation. In the grazing cattle, the elevation of miR-10b expression in the plasma was coincident with its elevation in the longissimus lumborum (LL) muscle. Expression of bovine-specific miR-2478, the most plasma-enriched miRNA, tended to be also upregulated in the muscle but not in the plasma. Furthermore, grazing caused the downregulated mRNA expression of predicted miR-10b and/or miR-2478 target genes, such as DNAJB2, PTEN, and SCD1. Thus, the feeding system used for JB cattle affected the c-miRNAs that could be indicators of grain feeding. Among these, miR-10b expression was especially associated with feeding-induced changes and with the expression of the potential target genes responsible for glucose homeostasis and intramuscular fat depot in the LL muscle of JB cattle.


Possible association of CYP17 gene polymorphisms with the onset of rheumatoid arthritis.
The etiologic role of sex hormones in rheumatoid arthritis (RA) has been discussed. Cytochrome P450c 17 alpha (CYP17) regulates steroidogenesis and the restriction fragment length polymorphisms (RFLPs) of the CYP17 gene are related to serum sex hormone production. In this study, the relationship between CYP17 gene RFLPs and RA was investigated. Genomic DNA was extracted from the peripheral blood of 91 male and 285 female patients with RA, as well as from 380 male and 579 female controls, and the RFLPs of the CYP17 gene (denoted as the A1 and A2 alleles) were determined. Clinical variables were recorded for the RA patients. There were no significant differences in CYP17 genotype distribution between the male RA patients and male controls, nor between the female RA patients and female controls. RA patients with the A2 allele tended to develop the disease at a younger age than those without (in men 50.1 vs 54.7 yrs, p = 0.15; in women 43.9 vs 47.4 yrs, p = 0.038). In women, having the A2 allele was a weak protective factor against developing RA at an older age (odds ratio: 0.63, 95% confidence interval: 0.41-0.95, p = 0.026). The RFLPs of the CYP17 gene may constitute a disease modifying factor through sex hormone production.


How do we talk to each other? Writing qualitative research for quantitative readers.
The growth of qualitative research holds the potential for vastly enriching our understanding of phenomena in the health sciences. However, the potential of this trend is hampered by a widespread inability of quantitative and qualitative researchers to talk to each other. The authors' concern in this area grows out of our experience reviewing small grant applications for the National Institute on Aging, where they frequently find qualitative research proposals scoring worse than do those using quantitative approaches. This article addresses practical problems in communicating qualitative research to readers whose training and experience is primarily quantitative. Two themes running through the discussion are the need for detail and the explicit tying of methodological strategies to research goals.


Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication.
To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori) eradication in a randomized, double-blinded, comparative clinical trial in China. A total of 215 H. pylori-positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid, 1000 mg amoxicillin bid, 100 mg bismuth pectin qid, and 500 mg levofloxacin qd); group B (n = 72) received the sequential therapy (20 mg omeprazole bid, 1000 mg amoxicillin bid, in 5 d, followed by 20 mg omeprazole bid, 500 mg tinidazole bid, 500 mg clarithromycin bid, for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid, 1000 mg amoxicillin bid, 500 mg clarithromycin bid). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. chi(2) test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies.


Coordination-Adaptive Polydentate Pseudorotaxane Ligand for Capturing Multiple Uranyl Species.
The propensity of uranyl for hydrolysis in aqueous environments prevents precise control of uranyl species in the scenarios of on-demand separation and tailored synthesis. Herein, using cucurbit[7]uril (CB[7]) as the macrocyclic molecule and 4,4'-bipyridine-N,N'-dioxide (DPO) as the string molecule, we propose a new kind of multidentate pseudorotaxane ligand, DPO@CB[7] for capturing uranyl species at different pH's. With the aprotic nature of DPO for metal coordination, the coordination ability of the DPO@CB[7] ligand is less affected by pH and can work in a wide range of pH's. Furthermore, by adaptive uranyl coordination, this aprotic pseudorotaxane ligand achieves effective recognition for different uranyl species ranging from monomeric to tetrameric originating from hydrolysis at varying pH's, and four novel uranyl-rotaxane compounds (URC1-4) are successfully obtained. Single-crystal X-ray diffraction analysis reveals that the DPO@CB[7] ligand coordinates with uranyl centers from monomeric to tetrameric in four different modes, as a result of structural flexibility of the DPO@CB[7] pseudorotaxane ligand. A detailed discussion for conformation flexibility of the DPO@CB[7] ligand has been conducted on the position changes of the DPO ligand trapped in the CB[7], which thus reveals good adaptivity of DPO@CB[7] that is noncovalently bonded as a supramolecular motif. In addition, characterization of the physicochemical properties of URC1 and URC2 with high phase purity, including powder X-ray diffraction (PXRD), infrared spectroscopy (IR), thermogravimetric analysis (TGA), and luminescence properties, are also provided. This work provides a good case of an adaptive pseudorotaxane ligand for the recognition and capture of different uranyl species and will bring valuable hints to the design of multifunctional supramolecular ligands for actinide separation in the future.


Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.
α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson's disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson's disease was higher than that of control patients. Notably, the lag time of patients with Parkinson's disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.


New carbon dates link climatic change with human colonization and Pleistocene extinctions.
Drastic ecological restructuring, species redistribution and extinctions mark the Pleistocene-Holocene transition, but an insufficiency of numbers of well-dated large mammal fossils from this transition have impeded progress in understanding the various causative links. Here I add many new radiocarbon dates to those already published on late Pleistocene fossils from Alaska and the Yukon Territory (AK-YT) and show previously unrecognized patterns. Species that survived the Pleistocene, for example, bison (Bison priscus, which evolved into Bison bison), wapiti (Cervus canadensis) and, to a smaller degree, moose (Alces alces), began to increase in numbers and continued to do so before and during human colonization and before the regional extinction of horse (Equus ferus) and mammoth (Mammuthus primigenius). These patterns allow us to reject, at least in AK-YT, some hypotheses of late Pleistocene extinction: 'Blitzkrieg' version of simultaneous human overkill, 'keystone' removal, and 'palaeo-disease'. Hypotheses of a subtler human impact and/or ecological replacement or displacement are more consistent with the data. The new patterns of dates indicate a radical ecological sorting during a uniquely forage-rich transitional period, affecting all large mammals, including humans.


Inhibition of coding region determinant binding protein sensitizes melanoma cells to chemotherapeutic agents.
We previously reported that malignant melanomas express high levels of the mRNA binding protein coding region determinant binding protein (CRD-BP). This molecule is important for the activation of anti-apoptotic pathways, a mechanism often linked to insensitivity to therapeutics. However, it is not known whether CRD-BP plays a role in the resistance of melanomas to anti-cancer treatment. Here we demonstrate that knockdown of CRD-BP with a specific sh-RNA enhances the effect of dacarbazine, temozolomide, vinblastine, and etoposide on both primary and metastatic melanoma cell lines. CRD-BP down-regulation contributes to cell sensitization by increasing apoptosis and diminishing melanoma cell growth in response to chemotherapeutic agents. Furthermore, inhibition of CRD-BP decreases microphthalmia-associated transcription factor (MITF) expression and reintroduction of MITF partially compensates for the absence of CRD-BP. These findings suggest that high expression of CRD-BP in melanoma cells confers resistance to chemotherapy and that these CRD-BP responses are mediated, at least in part, by MITF.


Crystallization of monoacylated proteins: influence of acyl chain length.
The crystallization of monoacylated proteins has been investigated using a model system. Acylated derivatives of bovine pancreatic ribonuclease A, differing in their acyl chain lengths (10 to 16 carbon atoms), have been prepared using reverse micelles as microreactors. With one fatty acid moiety per polypeptide chain, covalently attached to the NH2 terminus of the protein, all the modified proteins have similar enzymatic activity and hydrodynamic radius as the native protein. Only the caprylated derivative can give crystals which diffract to high resolution. The resolved structure indicates that: (i) the protein folding is not modified by the chemical modification, (ii) the capryl moiety is not buried within the molecule but available for external interactions. Dynamic light scattering experiments on concentrated solutions show that the protein-protein interactions are dependent on acyl chain length. Proteins with the longest attached chains (14 and 16 carbon atoms) tend to self-associate through acyl group interactions.


Prostate cancer-associated markers.
Immunodiagnosis of prostate cancer is at a more advanced stage than that of most other tumors. Two well-known markers, prostatic acid phosphatase and prostate-specific antigen, have been used in the clinical management of patients. Prostate-specific antigen is a more sensitive and reliable marker than prostatic acid phosphatase. Serum prostate-specific antigen is effective in monitoring disease status, predicting recurrence, and detecting residual disease. Prostate-specific antigen is a tool for the histological differential diagnosis of metastatic carcinomas, especially in the identification of metastatic prostate tumor cells in distant organs and in the differentiation of primary prostate carcinoma from poorly differentiated transitional cell carcinoma of the bladder. Few data on biological function are available. Prostatic acid phosphatase functions as a phosphotyrosyl-protein phosphatase and prostate-specific antigen as a protease. Physiological function in the prostate remains to be elucidated. Several of the prostate-specific and prostate-tumor-associated antigens, as well as a putative prostate tumor-specific antigen, as recognized by monoclonal antibodies are available. Clinical evaluation of these potential markers is not yet available.


ABA-Dependent and ABA-Independent Functions of RCAR5/PYL11 in Response to Cold Stress.
Arabidopsis thaliana has 14 abscisic acid (ABA) receptors-PYR1/PYLs/RCARs-which have diverse and redundant functions in ABA signaling; however, the precise role of these ABA receptors remains to be elucidated. Here, we report the functional characterization of RCAR5/PYL11 in response to cold stress. Expression of RCAR5 gene in dry seeds and leaves was ABA-dependent and ABA-independent, respectively. Under cold stress conditions, seed germination was negatively affected by the level of RCAR5 expression, which was dependent on ABA and was regulated by HAB1, OST1, and ABI5-downstream components of RCAR5 in ABA signaling. Leaves of RCAR5-overexpressing plants showed enhanced stomatal closure-independent of ABA-and high expression levels of cold, dehydration, and/or ABA-responsive genes compared to those of wild-type; these traits conferred enhanced freezing tolerance. Our data suggest that RCAR5 functions in response to cold stress by delaying seed germination and inducing rapid stomatal closure via ABA-dependent and ABA-independent pathways, respectively.