Antigenic and functional characterization of p57 produced by Renibacterium salmoninarum

Renibacterium salmoninarum, the causative agent of bacterial kidney disease, produces large quantities of a 57-58 kDa protein (p57) during growth in broth culture and during infection of salmonid fish. Biological activities of secreted p57 include agglutination of salmonid leucocytes and rabbit erythrocytes. We define the location of epitopes on p57 recognized by agglutination-blocking monoclonal antibodies (MAbs) 4C11, 4H8 and 4D3, and demonstrate that the majority of secreted p57 is a monomer that retains salmonid leucocyte agglutinating activity. The 3 MAbs bound a recombinant, amino-terminal fragment of p57 (211 aa) but not a carboxy-terminal fragment (315 aa) demonstrating that the neutralizing epitopes are located within the amino-terminal portion of p57. When combinations of the MAbs were used in an antigen capture ELISA, the epitopes recognized by the 3 MAbs were shown to be sterically separate. However, when the same MAb was used as both the coating and detection MAb, binding of the biotinylated detection MAb was not observed. These data indicate that the epitopes recognized by the 3 agglutination-blocking antibodies are functionally available only once per molecule and that native p57 exists as a monomer. Similar ELISA results were obtained when kidney tissues from 3 naturally infected chinook salmon were assayed. Finally, a p57 monomer was purified using anion exchange and size exclusion chromatography that retained in vitro agglutinating activity. A model in which p57 is released from R. salmoninarum as a biologically active monomer during infection of salmonid fish is proposed

Methionine Adenosyltransferase I/III Deficiency in Portugal: High Frequency of a Dominantly Inherited Form in a Small Area of Douro High Lands

Methionine adenosyltransferase deficienc(MAT I/III deficiency) is an inborn error of metabolism resulting in isolated hypermethioninemia, and usually inherited as an autosomal recessive trait, although a dominant form has been reported in several families. During the last 6 years, approximately 520,000 newborns were screened in the Portuguese Newborn Screening Laboratory by MS/MS, and 21 cases of persistent hypermethioninemia were found. One case was confirmed to be a deficiency of cystathionine b-synthase and 20 cases were confirmed by MAT1A gene analysis to have an elevation of methionine due to MAT I/III deficiency, which indicates an incidence for this condition of 1/26,000. Twelve of the MAT I/III deficient newborns, belonging to 11 families, were identified in the northern region of Portugal and sent to the same treatment center, where they are under follow-up. Clinical, biochemical, and genetic characteristics of individuals from these 11 families are presented. Plasma methionine and homocysteine concentrations were found to be moderately increased in all newborns, and molecular analysis revealed that they all were heterozygous for R264H mutation. Normal growth,development, and neurological examination were observed in all cases, and cerebral MRI performed in six cases revealed myelination abnormalities in one case. Plasma methionine concentration for all 12 cases was always below 300 mM, and they are all on a normal diet for their age

Comparisons of attitudes and practices between obese and normal weight women in Taiwan

This study was designed to obtain baseline data regarding self-reported body image, attitudes toward overweight people, and dietary behaviors of normal-weight and obese women in Taiwan. Fifty obese women (BMI ≧ 27) and age-matched normal-weight women participated in this study. Written questionnaires were used for data collection. Simple frequency and t-test were used to analyze data. In general, the majority of normal-weight women perceived themselves as being heavier than their actual body weight. The normal-weight group had more high inaccurate images of their bodies than that of the obese group (72% vs. 24%). Obese and normal-weight women had similar attitudes to overweight people, but some of their attitudes showed significant differences. Obese women would prefer to consume more fried foods and drink sugar-containing foods than would normal-weight women (p < 0.05). Education about accurate perceptions of what is normal weight for women and adopting energy-diluted foods for obese women is needed in the future

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.This work was supported by National Institutes of Health grants R01-CA122443, P50-CA136393, P30-CA15083, and the Fred C. and Katherine B. Andersen Foundation. We thank Gary Kenney, M.D. for pathology review of tumor tissue. We thank Craig Luccarini, Caroline Baynes from University of Cambridge for assisting our sample sequencing

Is equal access to higher education in South Asia and sub-Saharan Africa achievable by 2030?

Higher education is back in the spotlight, with post-2015 sustainable development goals emphasising equality of access. In this paper, we highlight the long distance still to travel to achieve the goal of equal access to higher education for all, with a focus on poorer countries which tend to have lower levels of enrolment in higher education. Analysing Demographic and Health Survey data from 35 low- and middle-income countries in sub-Saharan Africa and South Asia, we show wide wealth inequalities in particular, with few if any of the poorest gaining access to higher education in some countries. We further identify that wealth and gender inequalities interact and tend to be wider in countries where levels of higher education are higher. This implies that expansion in access to higher education may predominantly benefit the rich, unless measures are taken to tackle inequalities. We find that that the rates of increase necessary for the attainment of the equal access goal by 2030 are particularly high. They pose a particularly difficult challenge given the access inequalities present from primary and secondary education in a wide majority of countries in our analysis. We therefore suggest that any measures aimed at attaining the goal need to tackle inequalities in access within a system-wide approach, focusing on the level of education at which inequalities initially manifest, alongside higher education.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10734-016-0039-

30-Day Mortality and Cardiopulmonary Complication Rates in Patients Undergoing Emergency Surgery with Perioperative SARS-CoV-2 Infection

INTRODUCTION AND OBJECTIVE: Continued vigilance of operative outcomes in COVID-19 patients is important given the relative novelty of the SARS-CoV-2 infection. We sought to evaluate the 30-day mortality and cardiopulmonary complication rates in patients undergoing emergency surgery with perioperative COVID-19, in comparison to a control group of medically managed COVID-19 patients that did not require a surgical intervention. METHODS: A retrospective chart review at a single tertiary-care hospital in Michigan was undertaken. Patients who had tested positive for SARS-CoV-2 infection either 7 days before or within 30 days after surgery during March-May 2020 were included in the study (n=52). Propensity score matched (1:6) patients who had been positive for SARS CoV-2 infection during this time-period but did not undergo surgery served as controls (n=314). The primary endpoint was 30-day mortality. Secondary endpoints included cardiac and pulmonary complications. Multivariable logistic regression analyses were utilized to account for baseline differences. RESULTS: The 30-day mortality (17.3% vs 13.1%, p=0.408) and cardiac (28.9% vs 19.1%, p=0.107) and pulmonary complication (55.8% vs 49.4%, p=0.392) rates were similar in the surgical and the non-surgical groups. Multivariable analyses confirmed that emergency surgical intervention was not associated with increased odds for any of the studied adverse events (p\u3e0.10 for all 3 endpoints). CONCLUSIONS: Our analysis of 366 novel coronavirus patients demonstrates that patients undergoing emergency surgery with SARS-CoV-2 infection do not have an increased risk for 30-day mortality and cardiopulmonary complications compared to their counterparts that do not require surgery. The importance of this study is that an emergency intervention does not portend a poorer prognosis among patients with a confirmed SARS-CoV-2 Infection

Newborn Screening for Homocystinuria Revealed a High Frequency of MAT I/III Deficiency in Iberian Peninsula

Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375120/Homocystinuria due to cystathionine β-synthase deficiency or "classical homocystinuria" is a rare autosomal recessive condition resulting in altered sulfur metabolism with elevated methionine and homocysteine in plasma and homocystine in urine. This condition is characterized by a high clinical heterogeneity, which contributes to late clinical diagnosis, usually only made after irreversible damage has occurred. Treatment is effective if started before clinical symptoms. The analysis of methionine levels by tandem mass spectrometry (MS/MS) allows the newborn screening for homocystinuria, but false-positive results can be frequently obtained and lead to the unwanted identification of methionine adenosyl transferase (MAT I/III) deficiency. This latter condition is biochemically characterized by isolated persistent hypermethioninemia, accompanied in some individuals with slightly elevated levels of homocysteine in plasma. A dominant form of MAT I/III deficiency, associated with mutation p.R264H, seems to be very frequent in the Iberian Peninsula and usually has a clinically benign course. Both these metabolic disorders are screened in Galicia and Portugal since the introduction of the MS/MS technology, in 2000 and 2004, respectively, resulting in the identification of three patients with classical homocystinuria and 44 patients with MAT I/III deficiency. All but one heterozygous parent of MAT I/III patients, identified with the p.R264H mutation, are healthy adults around the age of 30/40. The implementation of a second-tier test for homocysteine in dried blood spots would considerably reduce the number of MAT I/III-deficient patients identified and improve the specificity and positive predictive value for classical homocystinuria screening

The effect of spiritual healing on in vitro tumour cell proliferation and viability – an experimental study

Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation of cells to five different doses of healing or control. Researchers conducting the assays and statistical analyses were blinded to the experimental conditions. Main outcome measures were MTT viability, 3H-thymidine incorporation and counts of an adherent human breast cancer cell line (MCF-7), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all three experimental days, doses, assays, and cells, 34 (51.6%) of 66 independent comparisons showed differences in the hypothesised direction (P=0.90). The average effect size across cell lines, days, assays, and doses approached zero (Cohen's d=−0.01). The results do not support previous reports of beneficial effects of spiritual healing on malignant cell growth in vitro. Reported beneficial effects of spiritual healing on the well-being of cancer patients seem more likely to be mediated by psychosocial and psychophysiological effects of the healer–patient relationship