Loss of MAGEC3 Expression Is Associated with Prognosis in Advanced Ovarian Cancers.
Rare variants in MAGEC3 are associated with BRCA negative, early-onset ovarian cancers. Given this association, we evaluated the impact of MAGEC3 protein expression on prognosis and transcription. We quantified normal and tumor protein expression of MAGEC3 via immunohistochemistry in n = 394 advanced ovarian cancers, assessed the correlation of these values with clinicopathologic and immunological features and modeled survival using univariate and multivariate models. To extend these results, we quantified MAGEC3 protein expression in n = 180 cancers and used matching RNA sequencing data to determine MAGEC3-associated differentially expressed genes and to build an RNA-based model of MAGEC3 protein levels. This model was tested in a third independent cohort of patients from TCGA's OV dataset (n = 282). MAGEC3 protein was sporadically lost in ovarian cancers, with half of the cases falling below the 9.5th percentile of normal tissue expression. Cases with MAGEC3 loss demonstrated better progression-free survival [HR = 0.71, p = 0.004], and analyses performed on predicted protein scores were consistent [HR = 0.57 p = 0.002]. MAGEC3 protein was correlated with CD8 protein expression [Pearson's r = 0.176, p = 0.011], NY-ESO-1 seropositivity, and mRNA expression of tumor antigens at Xq28. Results of gene set enrichment analysis showed that genes associated with MAGEC3 protein expression cluster around G2/M checkpoint (NES = 3.20, FDR < 0.001) and DNA repair (NES = 2.28, FDR < 0.001) hallmark pathways. These results show that MAGEC3 is a prognostic biomarker in ovarian cancer.


Transient NOE enhancement in solid-state MAS NMR of mobile systems.
It has been known that the heteronuclear cross-relaxation affects the dilute S spin magnetization along the longitudinal direction, causing an overshoot phenomenon for those mobile systems in spin-lattice relaxation rate measurements. Here, we analyze the Solomon equations for an I-S system and derive the transient cross relaxation effect as to when an overshoot phenomenon would take place and what the maximum enhancement could be at the time of the overshoot. In order to utilize such a transient nuclear Overhauser effect (NOE), we first time apply it to dynamic solid samples by inverting the 1H magnetization prior to the excitation of the S spin. It is found that the overshoot depends on the ratio of the I and S spin-lattice relaxation rates, i.e. RSS/RII. When RSS/RII≫1, the maximum enhancement factor for transient NOE could be larger than that obtained in steady-state NOE experiments. Furthermore, transient NOE appears to be more efficient in terms of sensitivity enhancement of dilute spins in solid-state NMR of mobile systems than the traditional cross polarization scheme whose efficiency is greatly compromised by molecular mobility. A sample of natural abundance l-isoleucine amino acid, in which the spin-lattice relaxation rates for the four methyl carbons are different, has been used to demonstrate sensitivity enhancement factors under various experimental schemes.


Pandemics and the English Language: Concepts Critical for Conversing About COVID-19.
We consider the multiple senses of several key terms that are used to discuss the ongoing COVID-19 pandemic and clarify meanings of the corresponding concepts. Topics addressed include: 1) the meaning of immunity to an infectious agent in varying medical and scientific contexts, 2) the scientific factors that influenced the rapid generation and clinical implementation of safe and effective vaccines for COVID-19, 3) the difference between mutational abrogation of reactivity with B- or T-cell antigen receptors (immune escape) versus active interference with host immune mechanisms mediated by gene products encoded within the genome of the infectious agent (immune evasion), 4) the different ways by which the COVID-19 pandemic has "caused" deaths, and 5) briefly, the challenge of precisely defining the term pathogen.


Slow Pathway Radiofrequency Ablation Using Magnetic Navigation: A Description of Technique and Retrospective Case Analysis.
The Magnetic Navigation System (MNS) catheter was shown to be stable in the presence of significant cardiac wall motion and delivered more effective lesions compared to manual control. This stability could potentially make AV junctional re-entrant tachycardia (AVNRT) ablation safer. The aim of this study is to describe the method of mapping and ablation of AVNRT with MNS and 3-D electro-anatomical mapping system (CARTO, Biosense Webster, Diamond bar, CA, USA) anatomical mapping, with a view to improve the safety of ablation. The method of precise mapping and ablation with MNS is described. Consecutive AVNRT cases (n=30) from 2012 January to 2015 November, in which magnetic navigation was used, are analysed. Ablation was successful in 27 (90%) out of 30 patients. In three cases, ablation was abandoned due to the proximity of the three-dimensional His image to the potential ablation site. No complications, including AV nodal injury, occurred. The distance from the nearest His position to successful ablation site in both LAO and RAO projections of CARTO images was 26.4±8.8 and 27±7.7mm respectively. Only in two (9%) patients, ablation needed to be extended superior to the plane of coronary sinus ostium, towards the His bundle region, to achieve slow pathway modification. AVNRT ablation with MNS allows for accurate mapping of the AV node and stable ablation at a safe distance, which could help avoid AV nodal injury. We recommend this modality for younger patients with AVNRT.


Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life.
Melanoma accounts for > 79% of skin cancer-related deaths, although it accounts for only 4% of skin cancer incidence. Given the potential for lethality, it is likely that patients with melanoma may experience significant emotional distress. The current study was designed to determine the effect of a cognitive-behavioral intervention on distress and health-related quality of life (HRQOL) in patients with melanoma who had medium-to-high distress. Forty-eight patients who had Global Severity Index scores >or= 60 2 months after their initial visit to the multidisciplinary melanoma clinic were randomized to receive either standard care or 4 sessions of a cognitive-behavioral intervention (CBI). Repeated assessments using the Brief Symptom Inventory, the Medical Outcomes Survey Short Form-36, and the State-Trait Anxiety Inventory occurred at baseline, at 2 months, and at 6 months after intervention for both groups. An intent-to-treat analysis did not reveal significantly lower distress in the CBI group at 2 months or 6 months of follow-up, although differences were noted in anxiety and HRQOL. An effect-of-intervention analysis did reveal lower levels of distress in the CBI group at 2 months, with differences approaching significance at 6 months. The four-session CBI significantly reduced distress and improved HRQOL for a period of 2 months in patients with melanoma who had medium-to-high distress, with improved general health evident 6 months after the intervention. Some variation in results was revealed in an intent-to-treat analysis. The initial evidence from the current study showed that a brief intervention may be effective for creating change in individuals with cancer who have increased distress, although further research is needed to identify the most optimal approach for delivering the intervention.


Breathing exercises improve post-operative pulmonary function and quality of life in patients with lung cancer: A meta-analysis.
Previous research has shown that breathing exercises may improve the prognosis and health status in patients with lung cancer by enhancing pulmonary function and quality of life (QOL). However, individually published results are inconclusive. The aim of the present meta-analysis was to evaluate the clinical value of breathing exercises on post-operative pulmonary function and QOL in patients with lung cancer. A literature search of Pubmed, Embase, the Web of Science and CBM databases was conducted from their inception through to October 2012. Crude standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the effect of breathing exercises. A total of eight clinical studies were ultimately included with 398 lung cancer patients. When all the eligible studies were pooled into the meta-analysis, there was a significant difference between the pre-intervention and post-intervention results of breathing exercises on post-operative pulmonary function; forced expiratory volume in 1 sec (FEV1): SMD, 3.37; 95% CI, 1.97-4.77; P<0.001; FEV1/FVC: SMD, 1.77; 95% CI, 0.15-3.39; P=0.032). Furthermore, the QOL in patients with lung cancer was significantly improved following the intervention with breathing exercises; there were significant differences between the pre-intervention and post-intervention results on the ability of self-care in daily life (SMD, -1.00; 95% CI, -1.467 to -0.52; P<0.001), social activities (SMD, -0.94; 95% CI, -1.73 to -0.15; P=0.02), symptoms of depression (SMD, -0.91; 95% CI, -1.25 to -0.57; P<0.001) and symptoms of anxiety (SMD, -0.91; 95% CI, -1.20 to -0.63; P<0.001). Results from the present meta-analysis suggest that breathing exercises may significantly improve post-operative pulmonary function and QOL in patients with lung cancer.


Pure red cell aplasia: The second hundred years.
Pure red cell aplasia (PRCA) is a rare hematologic syndrome, characterized by an isolated normocytic anemia with severe reticulocytopenia, and defined by absence or near absence of erythroid precursors in the bone marrow. First described in 1922, PRCA may be a primary autoimmune or clonal myeloid or lymphoid disorder, but may also be secondary to other disorders of immune dysregulation/autoimmunity, to infections, to neoplasms, or to drugs. Insights from the study of PRCA have helped illuminate the understanding of the regulation of erythropoiesis. This review summarizes the classification, diagnostic, and therapeutic approach to PRCA as it begins its second century, with a particular focus on opportunities and challenges provided by new developments in the role of T-cells and T-cell regulatory mutations; the role of clonal hematopoiesis; and new developments in therapy for refractory PRCA and PRCA associated with ABO incompatible stem cell transplantation.


Synthesis and structural characterization of Co2+ ions doped ZnO nanopowders by solid state reaction through sonication.
Cobalt ions doped zinc oxide nanopowder was prepared at room temperature by a novel and simple one step solid-state reaction method through sonication in the presence of a suitable surfactant Sodium Lauryl Sulphate (SLS). The prepared powder was characterized by various spectroscopic techniques. Powder XRD data revealed that the crystal structure belongs to hexagonal and its average crystallite size was evaluated. From optical absorption data, crystal fields (Dq), inter-electronic repulsion parameters (B, C) were evaluated. By correlating optical and EPR spectral data, the site symmetry of Co(2+) ion in the host lattice was determined as octahedral. Photoluminescence spectra exhibited the emission bands in ultraviolet and blue regions. The CIE chromaticity coordinates are also evaluated from the emission spectrum. FT-IR spectra showed the characteristic vibrational bands of Zn-O.


[Malignancy of familial adenomatous polyposis. Diagnosis and treatment].
Familial adenomatous polyposis with features of malignancy find in a 23 years old patient, whose diagnosis has been established on endoscopical basis. Total proctocolectomy is performed with terminal ileostomy. Histopathologically, the diagnosis is revealed, with establishing of multiple areas of malignancy in rectum and sigmoid colon. In the postoperative period, the patient is treated by pelvic radiotherapy and polychemotherapy. After one year, the clinical outcome is good, with weight gain 13 Kg and finishing high school. After two years, peritoneal carcinomatosis and one lung metastasis.


The prevalence of neuromyelitis optica in South East Wales.
Neuromyeltis optica (NMO) is a neuroinflammatory disorder considered rare in Caucasian populations. However, accurate population-based epidemiological data for NMO and NMO spectrum disorder (NMO-SD) from Western populations employing validated diagnostic criteria remain limited. We sought therefore to estimate the prevalence and clinical features of NMO in a north European Caucasian population in South East Wales. Patients were identified by a comprehensive, multistage ascertainment strategy employing a regional neuroinflammatory disease register, hospital diagnostic databases personal physician referrals and regional requests for anti-aquaporin-4 antibodies (anti-AQP4). Fourteen Caucasian patients (11 patients with NMO and three with NMO-SD) were identified in a population of 712,572 (19.6/million; 95% CIs: 12.2-29.7). There was an excess of females (female:male 12:2), 11/14 were anti-AQP4 positive and 5/14 had disease onset under the age of 20 years. This study suggests that NMO and related spectrum disorders are at least as frequent in Northern European populations as in non-Caucasian populations and that the demographic profile of prevalent patients differs from clinic-based cohorts.


Evaluation of vertical rectus muscles using ultrasound biomicroscopy.
To evaluate the accuracy of ultrasound biomicroscopy (UBM) in measuring the distance (in mm) from limbus to the insertion of vertical rectus muscles (superior rectus and inferior rectus compared with the "gold standard" surgical caliper at the time of surgery. Prospective, masked, observational study of 31 vertical rectus muscle insertions in which we compared the measurements from the limbus as measured by 50 MHz UBM, either preoperatively or at the time of anesthesia, with that measured by surgical caliper intraoperatively. Measurements (UBM and surgical) were evaluated by two different observers and analyzed using the Bland-Altman method. All UBM measurements were done by the same author. The intraclass correlation coefficient (ICC) and Pearson coefficient with 95% confidence intervals were used to quantify the degree of agreement between the two methods. Thirty-one vertical muscles were evaluated (13 superior rectus and 18 inferior rectus, of which 7 muscles were reoperations). The average for UBM measurements was 6.63 mm and for surgical caliper was 7.09 mm. The measurements for the two methods were all within +/-2 standard deviations of the mean. Only three measurements showed differences more than 1 mm. The ICC was 0.78 and Pearson coefficient was 0.85, indicating a "very good" correlation between the two methods. The longest distance from the limbus that could be accurately measured with the UBM was 12 mm. In one case a pseudotendon was differentiated from the true insertion of a previously recessed superior rectus muscle. The UBM and surgical measurements showed "very good" correlation when allowing for a margin of error of +/-1.0 mm between the two modalities, indicating that the UBM is a good predictor of the position of the vertical rectus muscles.


Rhodium-Catalyzed Synthesis of 4-Bromo-1,2-dihydroisoquinolines: Access to Bromonium Ylides by the Intramolecular Reaction of a Benzyl Bromide and an α-Imino Carbene.
Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the α-imino rhodium carbene formed in the presence of the rhodium catalyst.


EUS-guided choledochoduodenostomy using a lumen-apposing metal stent in a patient with preexisting duodenal stent and ascites.
Video 1EUS-guided choledochoduodenostomy using a lumen-apposing metal stent in a patient with preexisting duodenal stent and ascites.


A prediction model based on clinical and histological features for predicting recurrence in patients with stage I-II endometrial cancer after surgical treatment.
The study aimed to develop a prediction model combining clinical and histological features to predict recurrence in patients with stage I-II endometrial cancer (EC) after surgical treatment. A total of 746 stage I-II EC patients who had received primary surgical treatment at Taizhou People's Hospital between 2014 and 2018 were included and randomly divided as a Training cohort (n = 520) and a Validation cohort (n = 226) at a 7:3 ratio. Clinical features including age, body mass index, comorbidities, lymphadenectomy, and adjuvant treatment, and histological features including histologic type, myometrial invasion, cervical stromal invasion, and expression levels of Ki67, estrogen receptor (ER), progesterone receptor (PR), whey acidic protein 4-disulphide core domain 2 (WFDC2), and p53 were used to develop a prediction model for EC recurrence in the Training cohort using a multivariable Cox regression model. Model discrimination and calibration were further evaluated in the Validation cohort. EC recurrence was observed in 60 (11.54%) patients in the Training cohort with a median length of follow-up of 39 months. Age, adjuvant treatment, histologic type, cervical stromal invasion, and expression levels of Ki67, ER, PR, and WFDC2 were factors significantly associated with EC recurrence based on univariable Cox regression analysis. After a model selection by AIC in a stepwise algorithm, the final model incorporated the above predictors showed a C-index of 0.85 and fair calibration in the Training cohort. In the Validation cohort, the model still showed good discrimination power (C-index 0.80) but moderate calibration. The developed prediction model combining clinical and histological features can help to predict the EC recurrence in patients with stage I-II EC after surgical treatment.


Synthesis of Ag@Au core-shell NPs loaded with Ciprofloxacin as enhanced antimicrobial properties for the treatment and nursing care of Escherichia coli infection.
Bimetallic nanoparticles act as a multi-functional platform because of extraordinary properties that are most capable materials for biological applications. The present study reports the improvement of Au@ Ag-core shell nanoparticles filled in as seeds for ceaseless affidavit of silver molecules on its chitosan surface. The FT-IR spectrum techniques used to identify stretching vibrations of prepared NPs. The X-ray diffraction (XRD) outcomes show the medium crystalline shape and size of the Ag@Au loaded chitosan was around at 30 nm. The morphological structure of nanoparticles (NPs) was proved by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The Ag@Au contained chitosan results displayed the most elevated zone of hindrance 24 mm and lowest value 0.2 μg/mL of MIC against E. coli and treated with ciprofloxacin. The excellent antimicrobial results proven that the Ag@Au loaded chitosan can enhance the antibacterial activity. The combined Ag@Au core-shell NPs were intricately performed for cytotoxicity against human bosom malignant growth (MCF7) and cervical (HeLa) anticancer cell lines. The Ag@Au NPs may have incredible potential as viable antibacterial operators for pathogen control in clinics and nourishment preparing.


Imported Plasmodium falciparum malaria in HIV-infected patients: a report of two cases.
As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical signs of severe falciparum malaria, both with > 350 CD4 cell count/μl, absence of chemoprophylaxis and successful response. Factors like drug interactions and the possible implication of anti-malarial therapy bioavailability are all especially interesting in HIV-malaria co-infections.


Association between intensive care unit admission of a patient and mental disorders in the spouse: a retrospective matched-pair cohort study.
Previous prospective studies have suggested that spouses of patients who are admitted to the intensive care unit (ICU) have a high prevalence of mental disorders, termed post-intensive care syndrome-family (PICS-F). However, it remains unclear whether the patient's ICU admission is associated with the occurrence of mental disorders in the spouse outside of the prospective study setting. We therefore investigated the proportion of ICU patients' spouses who visited medical facilities for mental disorders and the association between ICU admission of a patient and mental disorders in the spouse using real-world data. This was a retrospective matched-pair cohort study using commercially available, routinely collected administrative claims data. As the study population, we identified all married couples (both wife and husband) who were registered in the database from 1 April 2012 to 31 August 2018 using family identification codes. We identified spouses of patients who were admitted to the ICU for more than 2 days as the exposure group and defined the date of admission to the ICU as the index date. We randomly matched four individuals in the non-exposure group with one individual in the exposure group. The primary outcome was any PICS-F-related mental disorder in the spouses within 6 months from the index date. As a sensitivity analysis, we also investigated the proportion and association of individuals (excluding spouses) with a history of mental disorders. Among 1,082,208 married couples, we identified 8490 spouses of ICU patients, and they were matched with 33,946 individuals. The proportion of any PICS-F-related mental disorder within 6 months from the index date was 12.8% in ICU patients' spouses and 11.3% in the matched individuals (adjusted odds ratio, 1.29; 95% confidence interval, 1.03-1.42). The sensitivity analysis showed significant associations between ICU admission and spouses' mental disorders. Spouses of patients who were admitted to the ICU had a slightly higher risk of mental disorders within 6 months than spouses of patients who were not admitted to the ICU.


Ongoing professional performance evaluation (OPPE) using automatically captured electronic anesthesia data.
The Massachusetts General Hospital (Boston), a large academic center providing anesthesia services for more than 49,000 procedures each year, created an Ongoing Professional Practice Evaluation (OPPE) process that could use readily available, automatically captured electronic information from its vendor-provided anesthesia information management system. The OPPE credentialing committee selected the following initial metrics: Blood pressure (BP) monitoring, end tidal CO2 monitoring, and timely documentation of compliance statements. Baseline data on the metrics were collected in an eight-month period (January 1, 2008-August 31, 2008). In February 2009 information on the metrics was provided to the department's staff members, and the ongoing evaluation process began. On the basis of three months of data, final reports for physicians being credentialed were distributed. Each report included a listing for each metric of the total number of compliant cases and noncompliant cases and a comparison by percentage to the baseline departmental evaluation. A summary statement indicated whether a physician's performance was within the group representing 95% of all department physicians. Noncompliant cases were listed by medical record number and case date so providers and reviewers could examine individual cases. A novel, automated, and continuous reporting system for physician credentialing that uses the existing clinical information system infrastructure can serve as a key element of a comprehensive clinical performance evaluation that measures both technical and generalizable clinical skill sets. It is not intended to provide a complete system for measuring competence but rather to serve as a first-round warning mechanism and metric scoring tool to identify problems and potential performance noncompliance issues.


Comparisons in perceived importance of and needs for maternal gestational weight information between african american and caucasian pregnant women.
This study compared the perceived importance of and needs for maternal gestational weight information between African American and Caucasian pregnant women. A secondary analysis of data from 113 pregnant women (82 African Americans and 31 Caucasians) attending an inner-city prenatal clinic was conducted for this study. Perceived importance of and needs for information were measured in five areas: (1) nutrition, (2) prenatal vitamins, (3) rest/activity balance, (4) exercise, and (5) appropriate weight gain. African American women demonstrated significantly higher perceived importance of and needs for information on rest/activity balance and appropriate weight gain than Caucasian women. Exercise information was rated lower in importance but was most needed by both African American and Caucasian women. Education programs about maternal gestational weight need to be cognizant of ethnic women's needs.


A review and analysis of the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase assay to determine the mutagenicity of chemical agents. A report of phase III of the U.S. Environmental Protection Agency Gene-Tox Program.
Published literature on the Chinese hamster ovary cell/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) assay from mid-1979 through June 1986 was reviewed and evaluated. Data from the papers considered acceptable include test results on 121 chemicals belonging to 25 chemical classes. A total of 87 chemicals were evaluated positive, 3 negative, and 31 inconclusive. Mutagenicity data on 49 of the 121 chemicals evaluated could also be compared with in vivo animal carcinogenicity data. 40 of the 43 reported animal carcinogens were considered mutagenic. Caprolactam, the only definitive noncarcinogen in the group of 49, was not mutagenic. The CHO/HGPRT assay was concluded to be an appropriate assay system for use in the screening of chemicals for genotoxicity.


Off-pump versus on-pump coronary surgery: final results from a prospective randomized study PRAGUE-4.
Off-pump coronary artery bypass surgery is becoming increasingly popular despite the lack of sufficient evidence from randomized trials. The aim of our prospective, randomized, single-center study was to examine the role of off-pump revascularization among nonselected patients. A total of 400 consecutive nonselected patients (mean age 63 years) scheduled for isolated coronary revascularization were randomized by a cardiologist into two groups: A (on-pump) and B (off-pump). The cardiac surgeon was allowed to change the operative technique at any time after randomization. The only exclusion criterion was an emergency procedure. The primary end point was any of the following within 30 days: death, myocardial infarction, stroke, or new renal failure requiring hemodialysis. The study was analyzed on the intention-to-treat principle. The primary end point occurred in 4.9% of patients in group A versus 2.9% in group B (not significant). Mortality was 1.1% in group A versus 2.0% in group B (not significant). Preoperative crossover occurred in 5.4% of patients in each group (not significant). Intraoperative conversion was necessary in 9.8% of patients in group B versus 1.1% of patients in group A (p < 0.001). Group B patients had fewer distal anastomoses (2.3 versus 2.7 in group A; p < 0.001), less blood loss (560 versus 680 mL; p < 0.001), lower postoperative creatine kinase MB levels (0.15 versus 0.56 microkat/L; p < 0.001) and lower total hospital costs (3,451 versus 4,387; p < 0.001). In our study off-pump technique was applicable in 85% of nonselected patients and is at least as clinically safe and effective as on-pump surgery.


BSP-PC (Bononian Satisfaction Profile--Prostate Cancer): development and validation of a "disease-specific" questionnaire for the evaluation of health-related quality of life in patients with prostate cancer.
Prostate cancer (PC) is the most common neoplasia in men over 50 years of age in western countries. Nowadays, since there are several alternative medical-surgical treatments for this cancer, health-related quality of life (HQoL) evaluation has become very important. The present study deals with the development and the validation of a questionnaire (BSP-PC), considering the HQoL in prostate cancer patients. The BSP-PC items are mainly related to the subjects' satisfaction. As far as we know, it does not exist any disease specific instrument based on such aspect. Questionnaire development: During three different meetings, with ten experts and twenty patients, we have defined the life aspects which are the most affected by prostate cancer. Subsequently we have created a first 40-item version of the BSP-PC. Patients were asked to fill in this particular questionnaire in addition to a generic and validated one (the EuroQol). A final 24 item questionnaire version, was finally achieved by other statistical analysis and meetings with experts. Questionnaire validation: the BSP-PC was filled in by 261 patients divided into 3 groups: "healthy" (57), "prostate cancer" (103), "other diseases" (100). Questionnaire development: participants' mean age was 59 years (N=71); 46% had prostate cancer, while 53% of the sample did not report notable diseases. The 24 items were selected on the basis of the following criteria: a) r>0.50, p<0.05 (correlation test re-test), b) p<0.05 (ANOVA presence vs absence of PC), c) r>0.50, p<0.05 (correlation with EuroQol). Questionnaire validation: participants' mean age was 68 years (N=261). Four factors were identified: 1) satisfaction about physical functionality (Crombach alpha=0.95), 2) satisfaction about sexual functionality (alpha=0.94), 3) satisfaction about social functionality (alpha=0.77), 4) satisfaction about urinary functionality (alpha=0.89); total Crombach alpha was 0.94. The BSP-PC questionnaire can be used as an instrument in the evaluation of HQoL in PC patients by principally considering their subjective satisfaction.


Differences in Dental Care Referral for Diabetic Patients Between General Practitioners and Diabetes Specialists in Japan, Analyzed from NSAID-Study 3.
Periodontal disease is a common inflammation worldwide and is not only the foremost cause of tooth loss but also a cause of deterioration of glycemic control in patients with diabetes mellitus. In addition, effective glycemic management improves the control of periodontitis infection. The aim of this study was to clarify whether awareness of the need to refer their patients with diabetes to dentists differs between general practitioners and diabetes specialists. This was achieved by secondary analysis of data from the 2018 Nationwide Survey on Actual Intervention for Type 2 Diabetes Mellitus (T2DM) by Japanese Practitioners (NSAID Study). Data from 380 general practitioners and 79 diabetes specialists who participated in the NSAID study and responded to the question of whether they referred T2DM patients to the dentist were analyzed in this study. The proportion of general practitioners who referred T2DM patients to dentists was significantly lower than that of diabetes specialists (35.4% vs. 64.1%, respectively). This result suggests that the general practitioners who participated in this study were less cognizant of oral hygiene in patients with diabetes than those who specialized in diabetes. It is also necessary to increase the opportunities for education of physicians who provide diabetic care to promote appropriate dental referrals.


Protease-activated quantum dot probes.
We have developed a novel nanoparticulate luminescent probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This construct may be useful for imaging in cancer detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Release of AuNPs by peptide cleavage restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47 h of exposure to 0.2 mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker.


Robotic-assisted laparoscopic nephrectomy.
The introduction of robot-assisted surgery has helped practitioners implement laparoscopic approached to complex retroperitoneal and renal surgery. Urologists are now more frequently completing surgeries such as radical nephroureterectomy, radical nephrectomy with IVC thrombectomy, and retroperitoneal lymphadentectomy via a laparoscopic approach than ever before. This review discusses the rational of the above surgeries as well as a technical step-by-step description of our robotic nephroureterectomy surgical approach.


Enhancement of Lipid Production of Chlorella Pyrenoidosa Cultivated in Municipal Wastewater by Magnetic Treatment.
Despite the significant breakthroughs in research on microalgae as a feedstock for biodiesel, its production cost is still much higher than that of fossil diesel. One possible solution to overcome this problem is to optimize algal growth and lipid production in wastewater. The present study examines the feasibility of using magnetic treatment for enhancement of algal lipid production and wastewater treatment in outdoor-cultivated Chlorella pyrenoidosa. Results confirmed that magnetic treatment significantly enhances biomass and lipid productivity of C. pyrenoidosa by 12 and 10 %, respectively. Application of magnetic field in a semi-continuous culture resulted in highly treated wastewater with total nitrogen maintained under 15 mg L-1, ammonia nitrogen below 5 mg L-1, total phosphorus less than 0.5 mg L-1, and CODCr less than 50 mg L-1. In addition, magnetic treatment resulted in a decrease of wastewater turbidity, an increase of bacterial numbers, and an increase of active oxygen in wastewater which might be attributed to the enhancement of growth and lipid production of C. pyrenoidosa.


Guillain-Barré syndrome associated with cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.
The association between cytomegalovirus (CMV) infection and the development of Guillain-Barré syndrome (GBS) in the setting of allogeneic hematopoietic stem cell transplantation (alloSCT) has been reported only occasionally. We describe here a 23-year-old patient diagnosed with acute myelogenous leukemia who underwent a partially HLA-mismatched alloSCT and soon after developed GBS along with a CMV infection. Serum autoantibodies to several ganglioside antigens were concomitantly detected. Despite therapy with ganciclovir and plasma exchanges, the patient's clinical condition rapidly deteriorated, and he died 3 weeks later with persisting CMV antigenemia. Although a coincidental association cannot be excluded, it could be speculated that a pathogenetic link exists between the 2 disorders. In this sense, molecular mimicry between viral antigens and neural host tissues could be postulated as the hypothetical mechanism underlying the triggering of the autoimmune disease in the present case.


Radioiodination and astatination of octreotide by conjugation labeling.
Octreotide was coupled to 3-iodobenzoyl and 3-iodonicotinoyl moieties to obtain [N-(3-iodobenzoyl)-D-Phe(1)]octreotide (IBO) and [N-(3-iodonicotinoyl)-D-Phe(1)]octreotide (INO), respectively. The IC(50) values for the binding of IBO and INO to CA20948 rat pancreatic tumor membranes were 0.90 and 0.13 nM, respectively, compared with 0.35 nM for octreotide itself. Starting from N-succinimidyl 3-[(131)I]iodobenzoate and N-succinimidyl 5-[(131)I]iodopyridine-3- carboxylate, [(131)I]IBO and [(131)I]INO were prepared in overall radiochemical yields of 35%-50%. Likewise, ¿N-(3-[(211)At]astatobenzoyl)-D-Phe(1)¿octreotide ([(211)At]ABO) was prepared in similar yield from N-succinimidyl 3-[(211)At]astatobenzoate. In vitro assays with AR42J rat pancreatic tumor cells demonstrated a higher retention of cell-internalized radioiodine activity for [(131)I]INO compared with [(125)I]IBO. Tissue distribution studies with both conjugates revealed low levels of activity in the thyroid suggesting that dehalogenation of these peptides was minimal.


Synthesis, X-ray Structure and Biological Studies of New Self-Assembled Cu(II) Complexes Derived from s-Triazine Schiff Base Ligand.
The two ligands 2-(1-(2-(4,6-dimorpholino-1,3,5-triazin-2-yl)hydrazono)ethyl)aniline (DMAT) and 2-(1-(2-(4,6-dimorpholino-1,3,5-triazin-2-yl)hydrazono)ethyl)phenol (DMOHT) were used to synthesize three heteroleptic Cu(II) complexes via a self-assembly technique. The structure of the newly synthesized complexes was characterized using elemental analysis, FTIR and X-ray photoelectron spectroscopy (XPS) to be [Cu(DMAT)(H2O)(NO3)]NO3.C2H5OH (1), [Cu(DMOT)(CH3COO)] (2) and [Cu(DMOT)(NO3)] (3). X-ray single-crystal structure of complex 1 revealed a hexa-coordinated Cu(II) ion with one DMAT as a neutral tridentate NNN-chelate, one bidentate nitrate group and one water molecule. In the case of complex 2, the Cu(II) is tetra-coordinated with one DMOT as an anionic tridentate NNO-chelate and one monodentate acetate group. The antimicrobial, antioxidant and anticancer activities of the studied compounds were examined. Complex 1 had the best anticancer activity against the lung carcinoma A-549 cell line (IC50 = 5.94 ± 0.58 µM) when compared to cis-platin (25.01 ±2.29 µM). The selectivity index (SI) of complex 1 was the highest (6.34) when compared with the free ligands (1.3-1.8), and complexes 2 (0.72) and 3 (2.97). The results suggested that, among those compounds studied, complex 1 is the most promising anticancer agent against the lung carcinoma A-549 cell line. In addition, complex 1 had the highest antioxidant activity (IC50 = 13.34 ± 0.58 µg/mL) which was found to be comparable to the standard ascorbic acid (IC50 = 10.62 ± 0.84 µg/mL). Additionally, complex 2 showedbroad-spectrum antimicrobial action against the microbes studied. The results revealed it to possess the strongest action of all the three complexes against B. subtilis. The MIC values found are 39.06, 39.06 and 78.125 μg/mL for complexes 1-3, respectively.


Staining with 0.05% neutral red reduces nutrient uptake by wheat roots.
A number of studies have used a 0.05% solution of neutral red to stain live roots so that short term root growth could be measured. These studies, which used a 5 or 10 min staining time, report no effects of the stain on plant properties such as growth, respiration, or nitrate uptake. This paper reports on two experiments conducted to determine whether this staining technique, with a 15 min stain time, affected macronutrient uptake of 6- and 7-week-old wheat (Triticum aestivum L.) plants grown in solution culture. The results showed that, compared with unstained controls, staining plants with 0.05% neutral red halted or halved nitrate uptake measured over a 4 h period the following day. Potassium uptake was also significantly reduced by staining. In the experiment with smaller plants nutrient uptake rate recovered 5 days after staining, but not in the second experiment with larger plants. Stained roots were 19% narrower than unstained roots, suggesting that the stain affected the root structure. We do not recommend the use of 0.05% neutral red staining, for wheat at least, in experiments where accurate measurement of nutrient uptake rate is important.


Expression of BmDHFR is up-regulated to trigger an increase in the BH4/BH2 ratio when the de novo synthesis of BH4 is blocked in silkworm, Bombyx mori.
Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals. BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. Sepiapterin reductase (SPR) and dihydrofolate reductase (DHFR) are crucial enzymes in the BH4 de novo synthesis pathway and salvage pathway, respectively. Dihydrobiopterin (BH2) is an oxidized product of BH4 metabolism. The ratio of BH4/BH2 is a key indicator of the stability of BH4 levels. The de novo pathway of BH4 synthesis is well-defined; however, little is known about the mechanisms of the salvage pathway in insects. Herein, we used the natural BmSPR mutant silkworm (lem) as a resource material. Our results reveal that the BmDHFR expression and the BH4/BH2 ratio were remarkably higher in lem as compared to the wild-type silkworm. In BmN cells, knockdown of BmSpr showed increased BmDHFR expression, while the BH4/BH2 ratio decreased after BmDhfr knockdown by RNAi. Furthermore, simultaneous RNAi of BmSpr and BmDhfr showed a further decrease in the BH4/BH2 ratio. These manifest that the expression of BmDHFR is up-regulated to trigger an increase in the BH4/BH2 ratio when the de novo synthesis of BH4 is blocked in silkworm. Additionally, the knockdown of BmSpr in wild-type silkworms also showed an increased BmDHFR level and BH4/BH2 ratio. Taken together, when the silkworm BH4 de novo synthesis pathway is blocked, the salvage pathway is activated, and BmDHFR plays an important role in maintaining the metabolic balance of silkworm BH4. This study enriches our understanding of the molecular mechanism of the BH4 salvage pathway and lays a good foundation for further studies on BH4 using the silkworm as a model insect.


Expression, purification, and functional characterization of a stable helicase domain from a tomato mosaic virus replication protein.
Tomato mosaic virus (genus, Tobamovirus) is a member of the alphavirus-like superfamily of positive-strand RNA viruses, which include many plant and animal viruses of agronomical and clinical importance. The RNA of alphavirus-like superfamily members encodes replication-associated proteins that contain a putative superfamily 1 helicase domain. To date, a viral three-dimensional superfamily 1 helicase structure has not been solved. For the study reported herein, we expressed tomato mosaic virus replication proteins that contain the putative helicase domain and additional upstream N-terminal residues in Escherichia coli. We found that an additional 155 residues upstream of the N-terminus of the helicase domain were necessary for stability. We developed an efficient procedure for the expression and purification of this fragment and have examined factors that affect its stability. Finally, we also showed that the stable fragment has nucleoside 5'-triphosphatase activity.


Differential arrival of newly synthesized apical and basolateral plasma membrane proteins in the epithelial cell line A6.
The labeling of specific cell surface proteins with biotin was used to examine both protein distribution and delivery of newly synthesized proteins to the apical and basolateral cell surface in A6 cells. Steady-state metabolic labeling with [35S]methionine followed by specific cell surface biotinylation demonstrated polarization of membrane proteins. The delivery of newly synthesized proteins to the apical or basolateral cell surface was examined by metabolic labeling with [35S]methionine using a pulse-chase protocol in combination with specific cell surface biotinylation. Newly synthesized biotinylated proteins at the apical cell surface reached a maximum after a 5 min chase, and then fell over the remainder of a 2 hr chase. The bulk flow of newly synthesized proteins to the basolateral membrane slowly rose to a maximum after 90 min. The detergent Triton X-114 was used to examine delivery of hydrophilic and hydrophobic proteins to the cell surface. Delivery of both hydrophilic and hydrophobic proteins to the apical cell surface reached a maximum 5 to 10 min into the chase period. The arrival of hydrophilic proteins at the basolateral surface showed early delivery and a maximum peak delivery at 120 min into the chase period. In contrast, only an early peak of delivery of newly synthesized hydrophobic proteins to the basolateral membrane was observed.


Comparison of treatment time versus patient satisfaction in at-home and in-office tooth bleaching therapy.
There are different approaches and treatment times to achieve tooth whitening. The purpose of this study was to evaluate the efficacy of different agents and the treatment time required to achieve participant satisfaction with at-home and in-office tooth whitening. Thirty participants were selected based on the shade of the anterior teeth (between A2 and A3.5; Vita Classic Shade Guide). Each participant received both in-office and at-home bleaching agents in a split-mouth design at both arches. In-office bleaching was performed in the maxillary quadrants, applying 35% hydrogen peroxide (HP35%) (right) and 35% HP with calcium (HP35%Ca) (left) for 40 minutes/week. Home bleaching was performed in mandibular quadrants using carbamide peroxide 10% (CP10%) (right) and CP22% (left) for 2 hours/day. Bleaching treatments were performed until participant satisfaction was achieved (maximum 6 sessions [S] in the dental office or 6 weeks [W] in the home). The shade was measured with a spectrophotometer before treatment, then at 2 and 4 weeks, and at the last week for at-home bleaching; and 1 week after the second, fourth, and last sessions for in-office bleaching. Student t and Tukey-Kramer tests were used (α=.05). All bleaching agents were effective for vital tooth whitening. No significant differences were observed for color changes between CP10% and CP22% or between HP35% and HP35%Ca for all periods. Treatment times required to achieve patient satisfaction for the in-office bleaching technique were 4S (12 participants), 5S (10 participants), and 6S (8 participants); and 4W (6 participants), 5W (8 participants), and 6W (16 participants) for the at-home bleaching technique. Treatment time to participant satisfaction ranged from 4 to 6 weeks regardless of the bleaching agent used in at-home and in-office therapy.


Improving quality of life for a patient with fibromyalgia and their caregiver: A protocol for the application of the integrative medical service model.
Patients with incurable diseases experience difficulty carrying out activities of daily living and rely on caregivers. Caregivers of patients with fibromyalgia (FM) are unable to understand the extent of the patients' suffering because the pain sites are invisible. To address this problem, this study will apply an integrative healthcare service model to a single FM case to manage pain and enhance the quality of life and, subsequently, gather feedback from different sources regarding the treatment. This paper presents the study protocol. We will conduct an observational study to gather quantitative and qualitative feedback from various perspectives regarding the application of an integrative healthcare service program for FM patients developed in Korea for an FM patient-caregiver pair. The program will comprise eight 100-minute weekly sessions, during which integrative services that combine Western and Oriental medicines (Korean traditional medicine) will be provided to enhance pain management and quality of life. The feedback collected after each session will be reflected in the next session' content. The results will comprise the feedback from the patient and caregiver in accordance with revisions made to the program. The results will provide basic data for optimizing an integrative healthcare service system in Korea for patients suffering from chronic pain owing to diseases such as FM.


Effectiveness of dry needling on reducing pain intensity in patients with myofascial pain syndrome: a Meta-analysis.
To summarize the literature about the effectiveness of dry needling (DN) on relieving pain and increasing range of motion (ROM) in individuals with myofascial pain syndrome (MPS). Papers published from January 2000 to January 2013 were identified through an electronic search in the databases MEDLINE, Dialnet, Cochrane Library Plus, Physiotherapy Evidence Data-base (PEDro) and Spanish Superior Council of Scientific Research (CSIC). The studies included were randomized controlled trials written in English and/or Spanish about the effectiveness of DN on pain and ROM in individuals with MPS. Out of 19 clinical trials that were potentially relevant, a total of 10 were included in the Meta-analysis. Regarding pain intensity reduction when measured before and immediately after the intervention, DN achieved improvement compared with the placebo treatment [d = - 0.49; 95% CI (- 3.21, 0.42)] and with the control group [d = - 9.13; 95% C (- 14.70, - 3.56)]. However, other treatments achieved better results on the same variable compared with DN, considering the measurements for pre-treatment and immediately after [d = 2.54; 95% CI (- 0.40, 5.48)], as well as the pre-treatment and after 3-4 weeks [d = 4.23; 95% CI (0.78, 7.68)]. DN showed a significantly increased ROM when measured before the intervention and immediately after, in comparison with the placebo [d = 2.00; 95% C (1.60, 2.41)]. However, other treatments achieved a significant better result regarding ROM when it was measured before the intervention and immediately after, as compared with DN [d = - 1.42; 95% CI (- 1.84, - 0.99)]. DN was less effective on decreasing pain comparing to the placebo group. Other treatments were more effective than DN on reducing pain after 3-4 weeks. However, on increasing ROM, DN was more effective comparing to that of placebo group, but less than other treatments.


Motivational interviewing: helping patients move toward change.
Motivational Interviewing (MI) is a valuable tool for nurses to help patients address behavior change. MI has been found effective for helping patients with multiple chronic conditions, adherence issues, and lifestyle issues change their health behaviors. For Christian nurses, MI is consistent with biblical principles and can be seen as a form of ministry. This article overviews the process of MI, stages of change, and offers direction for further learning.


Factors involved in the persistence of stress urinary incontinence from pregnancy to 2 years post partum.
To identify factors involved in the persistence of stress urinary incontinence (SUI) from pregnancy to 2 years post partum. In a longitudinal study at Donostia Hospital, San Sebastián, Spain, 458 primigravid women were recruited from April to October 2007. SUI was diagnosed via the 2002 International Continence Society definition. Severity was assessed via the Incontinence Severity Index, and impact on quality of life via the International Consultation on Incontinence Questionnaire. Means (Student t test and analysis of variance) and percentages (χ(2) and Fisher exact tests) were compared, and multiple logistic regression analysis was performed with variables that were significant or close to significant in a univariate analysis (P<0.2). Among 272 eligible women attending follow-up at 2 years post partum, 26 (9.5%) women reported persistent SUI since pregnancy. Incontinence severity was slight or moderate in most cases and the impact on quality of life was low. A higher body mass index (BMI) in pregnant women at term was the only factor found to be associated with persistent SUI (odds ratio 1.19; 95% confidence interval 1.08-1.32). Higher BMI in pregnant women at term was an independent risk factor for the persistence of SUI from pregnancy to 2 years post partum.


Long-term memory in Staphylococcus aureus α-hemolysin ion channel kinetics.
The kinetics of an ion channel are classically understood as a random process. However, studies have shown that in complex ion channels, formed by multiple subunits, this process can be deterministic, presenting long-term memory. Staphylococcus aureus α-hemolysin (α-HL) is a toxin that acts as the major factor in Staphylococcus aureus virulence. α-HL is a water-soluble protein capable of forming ion channels into lipid bilayers, by insertion of an amphipathic β-barrel. Here, the α-HL was used as an experimental model to study memory in ion channel kinetics. We applied the approximate entropy (ApEn) approach to analyze randomness and the Detrended Fluctuation Analysis (DFA) to investigate the existence of long memory in α-HL channel kinetics. Single-channel currents were measured through experiments with α-HL channels incorporated in planar lipid bilayers. All experiments were carried out under the following conditions: 1 M NaCl solution, pH 4.5; transmembrane potential of + 40 mV and temperature 25 ± 1 °C. Single-channel currents were recorded in real-time in the memory of a microcomputer coupled to an A/D converter and a patch-clamp amplifier. The conductance value of the α-HL channels was 0.82 ± 0.0025 nS (n = 128). The DFA analysis showed that the kinetics of α-HL channels presents long-term memory ([Formula: see text] = 0.63 ± 0.04). The ApEn outcomes showed low complexity to dwell times when open (ApEno = 0.5514 ± 0.28) and closed (ApEnc = 0.1145 ± 0.08), corroborating the results of the DFA method.


Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior.
Relationships of impulsive and nonimpulsive violent behavior to cerebrospinal fluid (CSF) monoamines and their metabolic concentrations were studied in thirty-six violent offenders. A relatively low 5-hydroxyindoleacetic acid (5HIAA) concentration was found in the CSF of impulsive violent offenders. This was not true for the offenders who had premeditated their acts. Other CSF monoamine or metabolite concentrations were not significantly different between the two groups. Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels. A low CSF 5HIAA concentration may be a marker of impulsivity rather than violence.


Compliance with temperature and time requirements during in-hospital distribution of blood components: A national survey among transfusion services.
Temperature and time conditions during storage and distribution of blood components (BC) and their permissible deviations are strictly regulated. The degree of compliance with these requirements in daily practice of transfusion services (TS) is not well known. We conducted a survey among Spanish hospital TS covering different aspects of BC management in their daily activity. Eighty-three TS managing 56 % of total transfusions answered the survey. Monitoring of red blood concentrates (RBC) temperature during in-hospital distribution was routinely performed by only 12 % of the TS. The main criterion for BC re-entry into the stock was the total time spent outside controlled temperature. Up to 41 % of the TS apply the "30-minute rule" to distributed RBC, while most services use a 60-minute rule for PC. No adverse events were detected when RBC that had remained longer than 30 or 60 min outside the TS were transfused. Fresh frozen plasma is usually thawed 2 h preissue and stored at 4 °C up to 24 h. In the Spanish context, the 30- and 60-minute rules for re-entry of RBC and PC into the TS stock are loosely followed. Feedback for a large number of TS suggests that the extension of the 30-minute RBC rule to at least 60 min is feasible, if other safety requirements are met. Flexibility with some requirements could help reduce product loss without deleterious effect on BC safety.


Yeast alpha-mating factor receptor and G-protein-linked adenylyl cyclase inhibition requires RAS2 and GPA2 activities.
Saccharomyces cerevisiae expresses two RAS gene products (RAS1 and RAS2) highly homologous to mammalian p21ras which mediate glucose-stimulated cyclic-AMP formation. Mating pheromone inhibits RAS-linked adenylyl cyclase activation and this is dependent upon the alpha-factor receptor (STE2) and its associated G-protein beta-subunit (STE4). We now show that this pheromone effect is independent of mating pathway signalling components "downstream" of STE4 but displays an absolute requirement for an additional G-protein alpha-subunit encoded by GPA2. alpha-mating factor effects also involve a specific suppression of normal RAS2 activity as the constitutively activated mutant RAS2vall9 as well as wild type. RAS1 are insensitive to inhibition. Interaction between GPA2, STE4-STE18, RAS2 and adenylyl cyclase in yeast could give important insight into signalling pathways controlling normal and oncogenic p21ras activity in man.


Cloning two P5CS genes from bioenergy sorghum and their expression profiles under abiotic stresses and MeJA treatment.
Sweet sorghum (Sorghum bicolor (Linn.) Moench) has promise as a bioenergy feedstock in China and other countries for its use in the production of ethanol as the result of its high fermentable sugar accumulation in stems. To boost biofuel production and extend its range, we seek to improve its stress tolerance. Proline acts as an osmolyte that accumulates when plants are subjected to abiotic stress. P5CS (Δ1-pyrroline-5-carboxylate synthetase) is a key regulatory enzyme that plays a crucial role in proline biosynthesis. We isolated two closely related P5CS genes from sweet sorghum, designated SbP5CS1 (GenBank accession number: GQ377719) and SbP5CS2 (GenBank accession number: GQ377720), which are located on chromosome 3 and 9 and encode 729 and 716 amino acid polypeptides, respectively. The homology between the two sweet sorghum P5CS genes was 76%. Promoter analysis of the two P5CS genes revealed that both sequences not only contained the expected cis regulatory regions such as TATA and CAAT boxes, but also had many stress response elements. Expression analysis revealed that SbP5CS1 and SbP5CS2 transcripts were up-regulated after treatment of 10-day-old seedlings of sweet sorghum with drought, salt (250mM NaCl) and MeJA (10μM). The expression levels of the both SbP5CS genes were significantly increased after 3-day drought stress. Under high salt treatment, peak SbP5CS1 expression was detected at 4h and 8h for SbP5CS2 in roots, while the trends of expression were nearly identical in leaves. In contrast, under drought and high salt stress, the up-regulated expression of SbP5CS1 was higher than that of SbP5CS2. When the seedlings were exposed to MeJA, rapid transcript induction of SbP5CS1 was detected at 2h in leaves, and the SbP5CS2 expression level increase was detected at 4h post-treatment. SbP5CS1 and SbP5CS2 also show different temporal and spatial expression patterns. SbP5CS2 gene was ubiquitously expressed whereas SbP5CS1 was mainly expressed in mature vegetative and reproductive organs. Proline concentration increased after stress application and was correlated with SbP5CS expression. Our results suggest that the SbP5CS1 and SbP5CS2 are stress inducible genes but might play non-redundant roles in plant development. The two genes could have the potential to be used in improving stress tolerance of sweet sorghum and other bioenergy feedstocks.


A systematic review on antibacterial activity of zinc against Streptococcus mutans.
The aim of this study was to systematically review the growth inhibition effectiveness of zinc against Streptococcus mutans. The main question was, "Does the zinc inhibit the growth of oral Streptococcus mutans in vitro? Literature search on PubMed, Medline, and science direct databases was carried out for in vitro studies published in English from 1990 to 2016, and the reported outcomes of minimum inhibitory concentration (MIC), minimum bactericidal concentrations (MBC), zone of inhibition (ZOI) and bacterial count method using colony forming unit (CFU) were used to assess the antibacterial effectiveness of zinc. Seventeen studies were included in this review. Seven studies reported MIC and MBC. Four studies reported ZOI, and eight studies reported CFU. MIC values using zinc chloride and zinc oxide nanoparticles were ranged from 0.025 to 0.2 mM and 0.390 to 500 ± 306.18 µg/ml respectively. MBC values using zinc oxide nanoparticles have ranged from 3.125 to 500 µg/ml. ZOI ranged from no inhibition zone to 21 ± 1.4 mm using 23.1% zinc oxide. A considerable reduction in the bacterial count was reported after adding zinc. However, only two studies have reported no inhibitory effect of zinc. This review indicated a significant growth inhibition effectiveness of zinc even at lower concentrations which indicate it's safely to be used in oral health products.


Conformal cubical 3D transformation-based metamaterial invisibility cloak: Erratum.
A correction to the definition of the constant a introduced after Eq. (4) in [J. Opt. Soc. Am. A30, 7-12 (2013)JOAOD60740-323210.1364/JOSAA.30.000007] is given.


Vaccine safety surveillance in Kenya using GAIA standards: A feasibility assessment of existing national and subnational research and program systems.
Active surveillance systems for monitoring vaccine safety among pregnant women address some of the limitations of a current passive surveillance approach utilized in low- and middle-income countries (LMIC). However, few active surveillance systems in LMIC exist. Our study assessed the feasibility of utilizing three existing data collection systems in Kenya for active surveillance of maternal immunization and to assess the applicability of Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions that were initially developed for clinical trials within these systems. We assessed applicability of GAIA case definition for maternal Tetanus Toxoid exposure, stillbirth, low birth weight, small for gestational age, Neonatal Invasive Blood Stream Infection (NIBSI), prematurity and neonatal death in two routine web-based health information systems (Kenya EMR and DHIS-2), and a web-based population-based pregnancy research platform (ANCOV1) in Kenya. All three HIS were capable of reporting selected outcomes to varying degrees of GAIA certainty. The ANCOV platform was the most robust in collecting and collating clinical data for effective maternal pharmacovigilance. The utilization of facility- and district-aggregated data limits the usefulness of DHIS-2 in pharmacovigilance as currently operationalized. While the Kenya EMR contained individual level data and meets the key considerations for effective pharmacovigilance, it was used primarily for HIV care and treatment records in a small proportion of health facilities and would require additional resources to expand to all antenatal care facilities and to link maternal and infant records. Population-based research studies may offer a responsive short-term option for implementing maternal vaccine pharmacovigilance in LMICs. However, the foundation exists for long-term capacity building within the national health electronic data systems to provide this critical service as well as ensure participation of the country in international studies on maternal vaccine safety.


Effects on cyclo-oxygenase of low and high dose aspirin.
The study was undertaken to develop clinically applicable methods to detect the influence of low dose treatment with acetylsalicylic acid (ASA) on the platelet function. The cyclooxygenase activity of the platelets was measured by determination of the metabolite 12-HHT after challenge with arachidonic acid. Two healthy subjects received 600 mg ASA in a single dose. Two hours after intake the salicylate concentration level in plasma was 600 nmol/ml, with a 90 per cent reduction after 24 hours. The platelet cyclooxygenase activity (12-HHT) was completely and irreversibly inhibited within two hours after ASA intake. Five subjects received 75 mg ASA for eight consecutive days. The salicylate concentrations two hours after the intake of the first and last tablet were within 65 and 71 nmol/ml plasma, indicating that no accumulation of salicylate occurred during the treatment period. The decrease in cyclooxygenase activity during low dose treatment varied in the different subjects between 60 and 90 per cent. The rate of recovery of cyclooxygenase activity after termination of the low dose ASA treatment was faster than after the large single dose.


[Cell to cell transfer of dense bodies induced by intracisternal infusion of leupeptin in rat cerebellum--quantitative and ultrastructural studies].
Previous studies have demonstrated that rats treated with a proteinase inhibitor, leupeptin (Leu), show an accumulation of lipofuscin (Lf)-like dense bodies in the neurons. The present study examines the quantitative and ultrastructural changes in the Lf-like dense bodies of Purkinje (P) cells and Bergmann (B) glia over 20 days following a 4-day regimen of Leu administration by intracisternal infusion. Toluidine blue staining revealed considerable Lf-like granules in both types of cells 1 day after Leu infusion. However, these granules had almost disappeared by 20 days after infusion. Quantitative analysis revealed a decrease in the amount of accumulated Lf-like granules in P cells whereas the granules in B glia increased 10 days after Leu infusion. Electron microscopic examination revealed the presence of Lf-like dense bodies on the plasma membranes of both the P cells and B glia. The present results suggest that Leu-induced dense bodies in P cells are transferred to B glia, indicating a possible route for the removal of Lf.


Camostat mesilate, a serine protease inhibitor, exerts aquaretic effects and decreases urinary exosomal AQP2 levels.
Serine proteases (SPs) play physiological roles in the kidney. We previously reported that a synthetic SP inhibitor, camostat mesilate (CM), suppressed sodium reabsorption in the renal tubule and showed natriuretic effects in aldosterone-infused rats. Here, we aimed to explore novel physiological roles of SPs in the renal tubule and understand the mechanism of actions of SP inhibitors, by administering CM to healthy rats. Sprague-Dawley rats were classified into control and CM (subcutaneous sustained-release pellet) groups and sacrificed on day 7. CM significantly increased urine volumes by approximately two-fold in a urinary sodium- and osmolyte excretion-independent manner, indicating the occurrence of free water excretion. Serum vasopressin, potassium, and calcium levels and the osmolality in the renal medulla, which all affect free water reabsorption in the renal tubule, remained unchanged after CM administration. CM decreased urinary exosomal AQP2 excretion, suggesting suppression of AQP2 activity in the collecting duct. These changes were reversed by desmopressin infusion. Water diuresis caused by CM was independent of its action on prostasin or TMPRSS4. Our results revealed the association of SP inhibition with free water handling and demonstrated that CM administration exerted diuretic effects with AQP2 downregulation, suggesting SP inhibitors as a new class of aquaretic drugs.


Changes in magnesium, zinc and calcium in men and women after an acute myocardial infarction.
The relations between different elements in acute myocardial infarction (MI) led us to determine erythrocyte (Erc) and/or plasma (Pl) concentrations of magnesium (Erc-Mg; Pl-Mg), zinc (Erc-Zn; Pl-Zn) and calcium (Pl-Ca) in 34 men and 8 women upon admission to hospital and then on days 2, 3, 6, 10 and 12. On day 1, these two groups were compared with 58 reference men or 53 reference women. The changes in the different variables from day 1 to day 12 were analyzed by one-way ANOVA. In MI men, from day 1 to day 12, all cations were significantly modified. In MI women, only Erc-Zn and Pl-Ca remained unchanged. In both populations, Pl-Mg, Erc-Mg and Pl-Zn increased significantly between day 1 and day 12.


Impacts of iron amendments and per-fluoroalkyl substances' bio-availability to the soil microbiome in wheat ecosystem.
Per-fluoroalkyl substances (PFASs) have become ubiquitous in farmland ecosystems and pose risks to agricultural safety, and iron is often applied to farmland soils to reduce the availability of pollutants. However, the effects of iron amendment on the availability of PFASs in the soil and on the soil microbiome are not well understood. Here, we investigated the responses of wheat soil containing PFASs to iron addition using a 21-day experiment. Our results showed that iron amendment enhanced PFAS availability (p < 0.05) and stimulated superoxide dismutase (SOD) activity in the wheat soil (p < 0.05), but iron amendment decreased the activities of soil catalase (CAT) and peroxidase (POD) (p < 0.05). Soil bacterial community was more structurally stable than fungal community in response to iron addition, while species' pools were more stable in fungi than in bacteria (p < 0.05). Finally, PFPeA's availability in the wheat soil was the most important abiotic factors driving community succession of iron-cycling bacteria (p < 0.05). These results highlighted the potential interactions among PFASs' availability and microbial iron cycling in wheat farmland soil ecosystems and provided guidance in farmland environmental conservation and management.


Ploidy distribution of tumour cells derived from induced and spontaneously arising metastases of a murine radiation-induced sarcoma, RIF-1.
Flow cytometric analysis of the X-radiation-induced sarcoma RIF-1 has shown that the parent tumour is composed of diploid and tetraploid subpopulations of cells, each capable of independent proliferation. We have now examined artificially induced and spontaneously arising metastases of the RIF-1 tumour and have found in both cases that, unlike the parent tumour from which they are derived, they exhibit a single level of ploidy which is stable throughout successive in vivo and in vitro passaging. This finding suggests that at least in this tumour system metastasis is a clonal event.


Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied climates and conditions.
To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra). Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study. 184 centers. 3,349 healthy women. In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center. Patch adhesion. In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study. The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.


The management of emergency hospital visits for inflammatory bowel diseases: A French national expert consensus report.
Management of inflammatory bowel diseases (IBD) in the emergency department is often suboptimal. To develop a national consensus checklist of indicators to facilitate decision-making in emergency departments concerning hospitalisation and referral for abdominopelvic computed tomography (CT). A Delphi survey was used to obtain consensus on a checklist of clinical and biological variables. 119 healthcare professionals experienced in treating IBD were invited to participate. Panellists were provided with a literature survey and invited to agree or disagree with items on a prototype checklist. Two successive rounds of voting were organised. The prototype checklist included fifteen clinical or laboratory indicators for hospitalisation or CT. Four indicators were not retained in the Delphi process and four additional indicators added. The final indicators retained were: abdominal signs/symptoms of disease exacerbation, intravenous morphine titration, fever, vomiting, dehydration, recent intestinal surgery, ano-perineal abscess, bowel obstruction, haemodynamic instability, anaemia, acute kidney failure and elevated C-reactive protein. Consensus for the retained indicators was >88%. Use of this consensus checklist for the management of IBD in the emergency department may help improve standards of care and thus reduce the burden of these diseases.


Cytotoxicity of anti-PP1Pk antibodies and possible relationship with early abortions of p mothers.
IgG and IgM anti-PP1Pk antibodies of human sera from p individuals were examined for their ability to agglutinate red blood cells (RBC) of various P phenotypes and to mediate ADCC of these RBC by human effector cells. Agglutinating antibodies were found in either the IgG or the IgM fraction, while ADCC active antibodies were found mainly in the IgG fraction and were essentially cytotoxic with Pk RBC. The possible relationship of these antibodies with early abortions of p mothers is discussed.


Phosphorylated CaMKII post-synaptic binding to NR2B subunits in the anterior cingulate cortex mediates visceral pain in visceral hypersensitive rats.
The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr²⁸⁶ protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr²⁸⁶ bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr²⁸⁶ protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state.


Treatment-outcome for synchronous head-and-neck and oesophageal squamous cell carcinoma.
Although head & neck and oesophageal carcinomas occur synchronously in up to 12%, almost no data on feasibility and outcome after radiotherapy are available. From 1989 to 2002, 24 patients were treated at Tuebingen University and Fulda hospital with a radiation based, curative approach. These were analyzed retrospectively. The median overall survival was 37 (1-69) months with a few long-term survivors with a median follow-up of 26 months for patients at risk. 7 local recurrences occurred. No major toxicity was seen. Even though the prognosis of synchronous head & neck and oesophageal carcinomas is grim, long-term survival is possible. A radiation-based approach is feasible and can be chosen for a curative treatment approach which we recommend.


Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials.
Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA. We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP. PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201. Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy. The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013.


Defect free strain relaxation of microcrystals on mesoporous patterned silicon.
A perfectly compliant substrate would allow the monolithic integration of high-quality semiconductor materials such as Ge and III-V on Silicon (Si) substrate, enabling novel functionalities on the well-established low-cost Si technology platform. Here, we demonstrate a compliant Si substrate allowing defect-free epitaxial growth of lattice mismatched materials. The method is based on the deep patterning of the Si substrate to form micrometer-scale pillars and subsequent electrochemical porosification. The investigation of the epitaxial Ge crystalline quality by X-ray diffraction, transmission electron microscopy and etch-pits counting demonstrates the full elastic relaxation of defect-free microcrystals. The achievement of dislocation free heteroepitaxy relies on the interplay between elastic deformation of the porous micropillars, set under stress by the lattice mismatch between Ge and Si, and on the diffusion of Ge into the mesoporous patterned substrate attenuating the mismatch strain at the Ge/Si interface.


The pro-fibrotic properties of transforming growth factor on human fibroblasts are counteracted by caffeic acid by inhibiting myofibroblast formation and collagen synthesis.
Fibrosis is a chronic disorder affecting many organs. A universal process in fibrosis is the formation of myofibroblasts and the subsequent collagen deposition by these cells. Transforming growth factor beta1 (TGFβ1) plays a major role in the formation of myofibroblasts, e.g. by activating fibroblasts. Currently, no treatments are available to circumvent fibrosis. Caffeic acid phenethyl ester (CAPE) shows a broad spectrum of biological activities, including anti-fibrotic properties in vivo in mice and rats. However, little is known about the direct effects of CAPE on fibroblasts. We have tested whether CAPE is able to suppress myofibroblast formation and collagen formation of human dermal and lung fibroblasts exposed to TGFβ1, and found that this was indeed the case. In fact, the formation of myofibroblasts by TGFβ1 and subsequent collagen formation was completely abolished by CAPE. The same was observed for fibronectin and tenascin C. The lack of myofibroblast formation is likely due to the suppression of GLI1 and GLI2 expression by CAPE because of diminished nuclear SMAD2/3 levels. Post-treatment with CAPE after myofibroblast formation even resulted in a partial reversal of myofibroblasts into fibroblasts and/or reduction in collagen formation. Major discrepancies were seen between mRNA levels of collagen type I and cells stained positive for collagen, underlining the need for protein data in fibrosis studies to make reliable conclusions.


Intraoperative adverse events as a risk factor for local recurrence of rectal cancer after resection surgery.
Failure to achieve a radical resection as well as intraoperative rectal perforation are important risk factors for local recurrence after rectal cancer surgery, but the importance of other intraoperative adverse events for the prognosis is unknown. The aim of this study was to assess the occurrence of intraoperative adverse events during rectal cancer surgery, and to determine whether these were associated with an increased risk of local recurrence. A retrospective population-based cohort study was undertaken, including all patients in Region Västra Götaland, Sweden, who had undergone primary resection surgery for rectal cancer diagnosed between 2010 and 2014, registered in the Swedish Colorectal Cancer Registry. Data were retrieved from the registry and through review of the medical records. In total, 1208 patients were included in the study of whom 78 (6%) developed local recurrence during the follow-up period of at least 5 years. Intraoperative adverse events were common and occurred in 62/78 (79%) of patients with local recurrence compared to 604/1130 (53%) of patients without local recurrence. In multivariate analysis intraoperative adverse events were found to be an independent risk factor for local recurrence of rectal cancer, as were nonradical resection, a high pathological T stage, the presence of lymph node metastases, type of surgery and refraining from rectal washout during anterior resection and Hartmann's procedure. Intraoperative adverse events were found to be an independent risk factor for local recurrence of rectal cancer and could possibly be used together with other known risk factors to select patients for intensified postoperative surveillance.


The effect of air pollution control devices in coal-fired power plants on the removal of condensable and filterable particulate matter.
Total particulate matter (TPM), including condensable and filterable particulate matter (CPM and FPM), is one of the pollutants that need to be controlled in the coal combustion process. In this study, CPM and FPM were sampled from sixteen coal-fired power units and two coal-fired industrial units. The removal effects of air pollution control devices equipped in the units on the migration and emission of particles were investigated by analyzing samples from inlets and outlets of apparatus. The average removal efficiency of TPM by dry-type dust removal equipment, wet flue gas desulfurization devices, and wet-type precipitators reached 98.57 ± 0.90%, 44.89 ± 15.01%, and 28.45 ± 7.78%, respectively. The removal efficiency of dry-type dust removal equipment and wet-type precipitators to TPM is mainly determined by the purification effect of FPM and CPM, respectively, and both types of particles contribute to the removal efficiency of desulfurization systems to total TPM. The concentrations of CPM (12.01 ± 5.64 mg/Nm3) and FPM (1.95 ± 0.86 mg/Nm3) emitted from ultra-low emission units were the lowest, and CPM is the dominant particle, especially the higher proportion of organic components in CPM.


Novel fusion antigen displayed-bacterial ghosts vaccine candidate against infection of Escherichia coli O157:H7.
Infection with Escherichia coli O157:H7 may develop into hemorrhagic colitis, or hemolytic uremic syndrome (HUS), which usually causes kidney failure or even death. The adhesion and toxins are the important virulent factors. In this study, a novel vaccine candidate rSOBGs was constructed based on the bacterial ghost (BG). rSOBGs maintained the integrity of cellular morphology and displayed the linear Stx2Am-Stx1B antigen on the surface of outer membrane. rSOBGs induced Stxs-specific IgA/IgG antibodies and stronger intimin-specific IgA/IgG antibodies effectively in sera in this study. In vivo, the rSOBGs provided the higher protection rate (52%) than native bacterial ghost-OBGs (12%) when challenged intragastricly with high dose (500 LD50) viable E. coli O157:H7. Meanwhile, the rSOBGs provided higher protection rate (73.33%) than OBGs when challenged with 2 LD50 even to 5 LD50 lysed E. coli O157:H7. In vitro, the rSOBGs-immunized sera possessed neutralizing activity to lysed pathogenic bacteria. Furthermore, the results of histopathology also displayed that the administration of rSOBGs have the ability to reduce or inhibit the adhesion lesions and toxins damages of organs. The novel vaccine candidate rSOBGs induced both anti-toxin and anti-adhesion immune protection, suggesting the possibility to prevent the infectious diseases caused by Escherichia coli O157:H7.


The Dandy-Walker malformation prenatal sonographic diagnosis and its clinical significance.
To determine the usual sonographic findings and clinical significance of the Dandy-Walker malformation (DWM) identified in utero, we reviewed seven proven cases diagnosed by prenatal ultrasound during a 6-year period. All patients demonstrated complete or partial absence of the cerebellar vermis and a posterior fossa cyst. Other central nervous system (CNS) findings included hydrocephalus (five cases) and agenesis of the corpus callosum (one case). Extra-CNS abnormalities were prospectively identified in 3 of 4 fetuses with multiple anomalies. Chromosomal analysis was performed on all four fetuses with multiple extra-CNS anomalies, yielding 2 abnormal karyotypes (trisomy 18 and mosaic trisomy 13). Fetal mortality was directly dependent on the presence of extra-CNS anomalies. Five fetuses ultimately died, including all four with multiple extra-CNS anomalies. The remaining two patients are alive at 1.5 and 6 years of age. We conclude that DWM has a distinctive sonographic appearance that can be identified by prenatal ultrasound and that identification of DWM should initiate a careful search for concurrent anomalies as well as consideration of chromosomal analysis.


The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells.
The human papillomavirus type 16 E5 protein (HPV16 E5) down-regulates surface expression of HLA-I molecules. The molecular mechanisms underlying this effect are so far unknown. Here we show that HPV16 E5 down-regulates HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. Immunoprecipitation experiments reveal that calnexin and HPV16E5 can be co-precipitated and that this association depends on the presence of a wild-type first hydrophobic region of E5. When an E5 mutant (M1) in which the first putative transmembrane helix had been disrupted was used for the transfections calnexin-E5 co-precipitation was strongly impaired. In addition, we show that the M1 mutant is only able to marginally down-regulate HLA-I surface expression compared to the wild-type protein. Besides, we demonstrate that E5 forms a ternary complex with calnexin and the heavy chain of HLA-I, which is mediated by the first hydrophobic region of the E5 protein. On the basis of our results we conclude that formation of this complex is responsible for retention of HLA-I molecules in the ER of the cells.


A longitudinal study of the serological and virological status of 18 women infected with cytomegalovirus.
18 women, of known seropositivity, have been followed for between 18 and 66 months (mean 50.2 months) for viral excretion and serological changes. CMV was isolated from 58/146 (39.7 per cent) cultures from various sites, mostly cervix. A total of 129 sera were obtained and each was titrated in the late antigen, early antigen and anti-complement immunofluorescence assays, as well as the complement fixation and microneutralisation tests. From 3 women virus was consistently re-isolated, from 3 others virus was never re-isolated and the remaining 12 women excreted virus intermittently during the period of study. No significant changes in antibody titres could be detected by any of the 5 serological assays in any woman during periods of viral excretion. This suggests that local reactivation of latent CMV infection is not associated with a demonstrable systemic antibody response. Inter-assay correlations were sought for each of the 10 possible combinations of pairs of tests. Significant correlations were found for most pairs of tests, with the notable exception fo those involving the early antigen test. This confirms that antibodies detected in this assay are distinct from those detected by the other 4 serological assays.


Defining the toxicological profile of 4-hydroxyphenylpyruvate dioxygenase-directed herbicides to Aedes aegypti and Amblyomma americanum.
Inhibitors targeting the 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzyme are well established herbicides and HPPD is also a primary enzyme within the tyrosine metabolism pathway in hematophagous arthropods, which is an essential metaboilic pathway post-blood feeding to prevent tyrosine-mediated toxicity. The objective of this study was to characterize the toxicity of triketone, pyrazole, pyrazolone, isoxazole, and triazole herbicides that inhibit HPPD to blood-fed mosquitoes and ticks. Topical exposure of nitisinone to blood-fed Aedes aegypti yielded high toxicity with an LD50 of 3.81 ng/insect (95% CI: 3.09 to 4.67 ng; Hillslope: 0.97, r2: 0.99), yet was non-toxic to non-blood fed (NBF) mosquitoes. The rank order of toxicity was nitisinone > tembotrione > pyrazoxyfen > tebuconazole > mesotrione against blood-fed Ae. Aegypti, but nitisinone was approximately 30-fold more toxic than other chemicals tested. We also assessed the toxicity of HPPD-inhibiting herbicides to the lone star tick, Amblyomma americanum and similarly, nitisinone was toxic to Am. americanum with a lethal time to kill 50% of subjects (LT50) of 23 h at 10 μM. Knockdown of the gene encoding the HPPD enzyme was performed through RNA-interference led to significant mortality after blood feeding in both, Ae. aegypti and Am. americanum. Lastly, a fluorescence assay was developed to determine relative quantities of L-tyrosine in Ae. aegypti and Am. americanum treated with HPPD inhibitors. L-tyrosine levels correlated with toxicity with nitisinone exposure leading to increased tyrosine concentrations post-blood feeding. Taken together, these data support previous work suggesting HPPD-inhibitors represent a novel mode of toxicity to mosquitoes and ticks and may represent base scaffolds for development of novel insecticides specific for hematophagous arthropods.


COVID-19 vaccine hesitancy and short-term and long-term intentions among unvaccinated young adults: a mixed-method approach.
Only 63.8% of Americans who are 18-to-24-years-old have been fully vaccinated for COVID-19 as of June 1, 2022. The Grand Forks County, North Dakota is facing a similar challenge. As of June 2022, 47% of individuals in the 19-to-29-year-old age group are vaccinated. Focusing on unvaccinated individuals in their 20s, Study 1 aims to understand the ways in which receiving COVID-19 vaccines is construed using qualitative interviews; and Study 2 compares the predictors of short-term vaccination intention (i.e., next month) with those of long-term vaccination intention (i.e., three to 5 years) using an online survey. For Study 1, we conducted five focus groups and four in-depth interviews via Zoom with a total of 26 unvaccinated individuals in their 20s living in the Grand Forks County. Constant comparison process was used to categorize data into themes and to recognize characteristics of the identified themes. The aim was to develop themes and associated characteristics. For Study 2, we conducted an online survey with a convenience sample of 526 unvaccinated individuals. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between attitudes, perceptions, and beliefs in misinformation and short-term and long-term vaccination intentions, accounting for demographics and socioeconomic status. In Study 1, two themes were identified: feelings of uncertainty sparked by profits and monetization and navigating the fear of the unknown. In Study 2, an increase in the confidence of COVID-19 vaccines showed significantly higher odds of short-term intention (OR = 2.658, 95%CI 1.770, 3.990) and long-term intention (OR = 1.568, 95% CI 1.105, 2.226). Believing in misinformation had significantly lower odds of short-term intention (OR = 0.712, 95%CI 0.513, 0.990), while more positive attitudes (OR = 1.439, 95% CI 1.024, 2.024), stronger preference in calculating the benefits of COVID-19 vaccines (OR = 2.108, 95% CI 1.541, 2.882), and greater perceived susceptibility (OR = 1.471, 95% CI 1.045, 2.070) to and severity of contracting COVID-19 (OR = 1.362, 95% CI 1.020, 1.820) were significantly associated with higher odds of long-term intention. Short-term and long-term intentions were predicted differently. Instilling strong confidence in COVID-19 vaccines should increase both short-term and long-term intentions.


Natural killer cell counts in primary HIV infection predicts disease progression and immune restoration after treatment.
The relationship between NK cell counts during primary infection and disease progression or immune restoration after antiretroviral treatment (ART) was explored. We followed 462 individuals with HIV infection and measured their NK, CD4+ T, CD8+ T cell counts and viral loads. Our data showed that individuals with high NK cell counts had much lower viral loads and higher CD4+ T cell counts. NK cell counts during primary infection were negatively correlated with viral set-point and viral loads at one-year-infection point, and positively correlated with CD4+ T cell counts at one-year-infection and one-year-ART point. Moreover, the NK cell counts during primary infection can predict HIV disease progression and immune restoration after ART. In conclusion, NK cell counts during primary infection represents a potential predictive biomarker to predict HIV disease prognosis in the clinic.


Influences of immobilization and footshock stress on pharmacokinetics of theophylline and caffeine in rats.
The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg-1) and caffeine (30 mg kg-1) administered orally were examined in rats. The immobilization stress for 30 min or 1 h immediately after oral administration caused marked immobilization period-related decreases in plasma theophylline concentrations during the absorption phase, but did not affect plasma caffeine concentrations. The ka and Cmax values for theophylline were significantly decreased, and the tmax was significantly increased. On the other hand, when the immobilization stress was loaded for 1 or 3 h before the oral administration, the plasma theophylline or caffeine concentrations were not affected. The footshock stress for 30 min immediately after oral administration did not significantly decrease plasma theophylline concentrations during the absorption phase. These results suggest that the pharmacokinetics of theophylline are influenced by strong stress, possibly due to the inhibition of its absorption from the gastrointestinal tract, but the pharmacokinetics of caffeine are not influenced by stress, probably due to its central action.


Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: the EVET trial.
Low-molecular weight heparins have different pharmacokinetic and pharmacodynamic characteristics and may vary in efficacy. We compared the efficacy of enoxaparin with that of tinzaparin in the management of non-ST-segment elevation acute coronary syndromes (NSTACS). A total of 438 patients with NSTACS were randomized to receive subcutaneous treatment with enoxaparin, 100 IU/kg twice daily (equivalent to 1 mg/kg twice daily; n = 220), or tinzaparin, 175 IU/kg once daily, (n = 218) for as long as 7 days. The primary composite end point was recurrent angina, myocardial infarction (or reinfarction), or death at day 7. Secondary end points were the primary end point at day 30 and the occurrence of individual events at days 7 and 30. The incidence of the primary end point was 12.3% in the enoxaparin group and 21.1% in the tinzaparin group (P =.015). At day 7, the rate of recurrent angina was lower with enoxaparin than with tinzaparin (11.8% vs 19.3%). At day 30, the incidences of the composite end point, recurrent angina, and myocardial infarction were also lower with enoxaparin, 17.7% vs 28.0% (P =.012), 17.3% vs 26.1% and 0.5% vs 2.8%, respectively. The rate of revascularization was lower in the enoxaparin group, 8.6% vs 17.9% (P =.010) at day 7 and 16.4% vs 26.1% (P =.019) at day 30. Rates of bleeding complications were similar in the 2 treatment groups. This study indicates a benefit of enoxaparin (100 IU/kg twice daily) as compared with tinzaparin (175 IU/kg once daily) in the treatment of patients with NSTACS, which is sustained for at least 30 days.