Vascular remodeling of the mouse yolk sac requires hemodynamic force

The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a^(–/–)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sa

Pathogenicity of Phoma betae isolates from red beet (Beta vulgaris) at seed farms in Canterbury, New Zealand

Phoma betae is an economically important pathogen of red beet causing pre-emergence seedling damping, leaf spot and root rot. However, the pathogenicity of P. betae is unknown in New Zealand despite the economic importance of this pathogen. Twenty-five isolates were collected from a survey of red beet seed farms in Canterbury, New Zealand during 2016/2017 and three of these PB101 (from seeds), PB103 (from roots) and PB106 (from leaves) were used for pathogenicity testing of two red-beet cultivars. Isolate PB106 was further used to investigate its effects on spinach and fodder beet as well as red beet under greenhouse conditions. All three P. betae isolates were pathogenic on both red-beet cultivars tested, causing leaf-spot symptoms. Isolates PB101 and PB106 produced significantly larger leaf-spot lesions (P<0.001) compared with PB103. Phoma betae isolate PB106 was pathogenic to both red-beet cultivars, spinach and fodder beet but fodder beet was less susceptible than the other species tested. Regardless of cultivar, P. betae is an important pathogen of beets and is capable of causing leaf spots

Preparing Humanities Students for Employment: Reimagining Career Exploration and Education through Ignatian Spirituality and Discernment

Graduate students in the humanities are hungry for career exploration as they face limited academic career options and feel called to work beyond the academy. Career preparation is typically left to graduate advisors, and then, the focus tends to be on academic career preparation. This article details how a required, introductory graduate class was reimagined to integrate career exploration using a framework at the heart of Ignatian spirituality and education: discernment. The authors outline the course and two assignments that can be adapted and applied to any graduate course. The authors share reflections on how the class has impacted their own professional and personal formation, and they end with heuristics for educators to use when preparing to teach similar graduate courses

Scotland Registry for Ankylosing Spondylitis (SIRAS) – Protocol

Funding SIRAS was funded by unrestricted grants from Pfizer and AbbVie. The project was reviewed by both companies, during the award process, for Scientific merit, to ensure that the design did not compromise patient safety, and to assess the global regulatory implications and any impact on regulatory strategy.Publisher PD

Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database.

Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers. Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12-2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93-1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64-1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon. Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers

Alternatives to Ciprofloxacin Use for Enteric Fever, United Kingdom

Alternatives to Ciprofloxacin Use for Enteric Fever, United Kingdo

The epidemiology of regional and widespread musculoskeletal pain in rural versus urban settings in those ≥55 years

Objectives: To examine whether the prevalence of regional and chronic widespread pain (CWP) varies with rurality and to determine the characteristics of persons in rural locations in whom pain is found to be in excess. Methods: Participants, aged ≥55 years, from participating general practices in seven different geographical locations in Scotland were sent a postal questionnaire. The 1-month prevalence of 10 regional pain conditions plus CWP was identified using body manikins. Differences in the prevalence of pain with differing rurality were examined using Chi2 test for trend. Thereafter, among the rural population, the relationships between pain and putative risk factors were examined using Poisson regression. Thus, results are described as risk ratios. Results: There was some evidence to suggest that the prevalence of CWP increased with increasing rurality, although the magnitude of this was slight. No large or significant differences were observed with any regional pain conditions. Factors associated with the reporting of CWP included poor general health, feeling downhearted most of the time and selected measures of social contact. Factors independently associated with CWP included female gender (risk ratio: 1.24; 95% confidence interval (CI): 0.997–1.55), poor self-rated health (risk ratio: 3.50; 95% CI: 1.92–6.39) and low mood (risk ratio: 1.54; 95% CI: 1.07–2.20). Also, having fewer than 10 people to turn to in a crisis was associated with a decrease in the risk of CWP – risk ratio: 0.68 (95% CI: 0.50–0.93) and 0.78 (95% CI: 0.60–1.02) for those with 5–10 and <5 people, respectively. Conclusions: This study provides no evidence that the prevalence of regional musculoskeletal pain is increased in rural settings, although there is some evidence of a modest increase in CWP. Risk factors for CWP are similar to those seen in the urban setting, including markers of general health, mental health and also aspects of social contact. It may be, however, that social networks are more difficult to maintain in rural settings, and clinicians should be aware of the negative effect of perceived social isolation on pain in rural areas