Antagonism between Notch and bone morphogenetic protein receptor signaling regulates neurogenesis in the cerebellar rhombic lip

BACKGROUND: During the embryonic development of the cerebellum, neurons are produced from progenitor cells located along a ventricular zone within dorsal rhombomere 1 that extends caudally to the roof plate of the fourth ventricle. The apposition of the caudal neuroepithelium and roof plate results in a unique inductive region termed the cerebellar rhombic lip, which gives rise to granule cell precursors and other glutamatergic neuronal lineages. Recently, we and others have shown that, at early embryonic stages prior to the emergence of granule cell precursors (E12), waves of neurogenesis in the cerebellar rhombic lip produce specific hindbrain nuclei followed by deep cerebellar neurons. How the induction of rhombic lip-derived neurons from cerebellar progenitors is regulated during this phase of cerebellar development to produce these temporally discrete neuronal populations while maintaining a progenitor pool for subsequent neurogenesis is not known. RESULTS: Employing both gain- and loss-of-function methods, we find that Notch1 signaling in the cerebellar primordium regulates the responsiveness of progenitor cells to bone morphogenetic proteins (BMPs) secreted from the roof plate that stimulate the production of rhombic lip-derived neurons. In the absence of Notch1, cerebellar progenitors are depleted during the early production of hindbrain neurons, resulting in a severe decrease in the deep cerebellar nuclei that are normally born subsequently. Mechanistically, we demonstrate that Notch1 activity prevents the induction of Math1 by antagonizing the BMP receptor-signaling pathway at the level of Msx2 expression. CONCLUSION: Our results provide a mechanism by which a balance between neural induction and maintenance of neural progenitors is achieved in the rhombic lip throughout embryonic development

Effects of a hospital-wide physician communication skills training workshop on self-efficacy, attitudes and behavior

Hospital systems interested in improving patient experience and physician engagement may look to physician communication skills training (CST) as a means of improving both. This study examines a 7.5-hour, multi-specialty, hospital-wide physician CST workshop in a large academic hospital system and its effects on participants’ self-efficacy, attitudes, and behaviors related to communicating with patients. Data was gathered from October 2014 through June 2016 through a web-based questionnaire sent to participants 6-weeks post-workshop which focused on skills taught in the course, attitudes toward communication training, and provider behaviors when communicating with patients. Along with demographic questions, a ten question retrospective pre-post format was used with a 5-point scale for the domains measured. Retrospective pre-post methodology may provide a more accurate assessment of a learners’ self-assessment of skills acquisition. A paired t-test was used to examine changes in participants’ self-efficacy, attitudes, and behaviors toward communicating with patients prior to and 6-weeks post-workshop. Linear regression was used to determine if there were any covariates that explained these changes. A total of 161 responses from 490 participants (21 medical specialties) were collected for a response rate of 32.8%. In 9 out of 10 domains measured, a significant change in self-efficacy, attitudes, and behaviors related to communicating with patients occurred (p\u3c. 05). There was no significant change in perceived time management/efficiency during visits. Our conclusion is that a 7.5 hour hospital-wide, multi-specialty physician CST can be effective in improving participants’ self-efficacy, attitudes, and behaviors toward communicating with patients

Review of best management practices for aquatic vegetation control in stormwater ponds, wetlands, and lakes

Auckland Council (AC) is responsible for the development and operation of a stormwater network across the region to avert risks to citizens and the environment. Within this stormwater network, aquatic vegetation (including plants, unicellular and filamentous algae) can have both a positive and negative role in stormwater management and water quality treatment. The situations where management is needed to control aquatic vegetation are not always clear, and an inability to identify effective, feasible and economical control options may constrain management initiatives. AC (Infrastructure and Technical Services, Stormwater) commissioned this technical report to provide information for decision- making on aquatic vegetation management with in stormwater systems that are likely to experience vegetation-related issues. Information was collated from a comprehensive literature review, augmented by knowledge held by the authors. This review identified a wide range of management practices that could be potentially employed. It also demonstrated complexities and uncertainties relating to these options that makes the identification of a best management practice difficult. Hence, the focus of this report was to enable users to screen for potential options, and use reference material provided on each option to confirm the best practice to employ for each situation. The report identifies factors to define whether there is an aquatic vegetation problem (Section 3.0), and emphasises the need for agreed management goals for control (e.g. reduction, mitigation, containment, eradication). Resources to screen which management option(s) to employ are provided (Section 4.0), relating to the target aquatic vegetation, likely applicability of options to the system being managed, indicative cost, and ease of implementation. Initial screening allows users to shortlist potential control options for further reference (Section 5.0). Thirty-five control options are described (Section 5.0) in sufficient detail to consider applicability to individual sites and species. These options are grouped under categories of biological, chemical or physical control. Biological control options involve the use of organisms to predate, infect or control vegetation growth (e.g. classical biological control) or manipulate conditions to control algal growth (e.g. pest fish removal, microbial products). Chemical control options involve the use of pesticides and chemicals (e.g. glyphosate, diquat), or the use of flocculants and nutrient inactivation products that are used to reduce nutrient loading, thereby decreasing algal growth. Physical control options involve removing vegetation or algal biomass (e.g. mechanical or manual harvesting), or setting up barriers to their growth (e.g. shading, bottom lining, sediment capping). Preventative management options are usually the most cost effective, and these are also briefly described (Section 6.0). For example, the use of hygiene or quarantine protocols can reduce weed introductions or spread. Catchment- based practices to reduce sediment and nutrient sources to stormwater are likely to assist in the avoidance of algal and possibly aquatic plant problems. Nutrient removal may be a co-benefit where harvesting of submerged weed biomass is undertaken in stormwater systems. It should also be considered that removal of substantial amounts of submerged vegetation may result in a sudden and difficult-to-reverse s witch to a turbid, phytoplankton dominated state. Another possible solution is the conversion of systems that experience aquatic vegetation issues, to systems that are less likely to experience issues. The focus of this report is on systems that receive significant stormwater inputs, i.e. constructed bodies, including ponds, amenity lakes, wetlands, and highly-modified receiving bodies. However, some information will have application to other natural water bodies

Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American Surveillance study (2000–2002)

Background Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. Methods Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000–2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). Results Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were ≤ 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum β-lactamase (ESBL) production among Enterobacteriaceae were low, \u3c6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% – 13.9%), Proteus mirabilis (0–34.7%), and Morganella morganii (1.6–20.7%) than other Enterobacteriaceae spp (1.5–21.3%). P. aeruginosa demonstrated marked variation in β-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. Conclusion There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections

Shared decision making in patients with low risk chest pain: prospective randomized pragmatic trial.

OBJECTIVE: To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome. DESIGN: Multicenter pragmatic parallel randomized controlled trial. SETTING: Six emergency departments in the United States. PARTICIPANTS: 898 adults (aged \u3e17 years) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing (451 were allocated to the decision aid and 447 to usual care), and 361 emergency clinicians (emergency physicians, nurse practitioners, and physician assistants) caring for patients with chest pain. INTERVENTIONS: Patients were randomly assigned (1:1) by an electronic, web based system to shared decision making facilitated by a decision aid or to usual care. The primary outcome, selected by patient and caregiver advisers, was patient knowledge of their risk for acute coronary syndrome and options for care; secondary outcomes were involvement in the decision to be admitted, proportion of patients admitted for cardiac testing, and the 30 day rate of major adverse cardiac events. RESULTS: Compared with the usual care arm, patients in the decision aid arm had greater knowledge of their risk for acute coronary syndrome and options for care (questions correct: decision aid, 4.2 v usual care, 3.6; mean difference 0.66, 95% confidence interval 0.46 to 0.86), were more involved in the decision (observing patient involvement scores: decision aid, 18.3 v usual care, 7.9; 10.3, 9.1 to 11.5), and less frequently decided with their clinician to be admitted for cardiac testing (decision aid, 37% v usual care, 52%; absolute difference 15%; P CONCLUSIONS: Use of a decision aid in patients at low risk for acute coronary syndrome increased patient knowledge about their risk, increased engagement, and safely decreased the rate of admission to an observation unit for cardiac testing.Trial registration ClinicalTrials.gov NCT01969240

Gynecological cancers: an alternative approach to healing

Grief and hope are two conflicting emotions that a patient recently diagnosed with cancer has to master. The real challenge for gynecologic oncologists is how to reach out. Conventional wisdom states that offering patients focus and belief when combating cancer in their lives allows them to embrace hope with greater confidence, which minimizes their grief. Three pictorial models are presented: ‘4-cusp approach’ model used at the initial consultation; ‘tapestry of bereavement or landscape of grief’ model at the postsurgery consultation; and ‘Venn-diagram’ model at any time during patient management. We have applied these models in our practice and believe that they can act as a fulcrum for the patient, the family and healthcare team around which therapy should be centered., Grief and hope are two emotions that a patient faces if diagnosed with cancer. The real challenge for the doctor is how to reach out and help the patient through this process. A doctor's role may be to offer focus and belief to the patient which may allow her to embrace hope with greater confidence. This will hopefully lessen the grief. We present three models which we believe can play a crucial part: ‘4-cusp approach’ used at the initial consultation; ‘tapestry of bereavement or landscape of grief model’ at the postsurgery consultation; and ‘Venn-diagram model’ at any time during care

Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.</p> <p>Methods</p> <p>A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged <it>in vivo </it>by intraperitoneal injection into immunocompetent Lewis rats, and <it>in vitro </it>culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. β-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.</p> <p>Results</p> <p>The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line <it>in vitro</it>, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear β-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.</p> <p>Conclusion</p> <p>This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.</p

The long-term impact of the MEMA kwa Vijana adolescent sexual and reproductive health intervention: effect of dose and time since intervention exposure.

BACKGROUND: Despite recent decreases in HIV incidence in many sub-Saharan African countries, there is little evidence that specific behavioural interventions have led to a reduction in HIV among young people. Further and wider-scale decreases in HIV require better understanding of when behaviour change occurs and why. The MEMA kwa Vijana adolescent sexual and reproductive health intervention has been implemented in rural Mwanza, Tanzania since 1999. A long-term evaluation in 2007/8 found that the intervention improved knowledge, attitudes to sex and some reported risk behaviours, but not HIV or HSV2 prevalence. The aim of this paper was to assess the differential impact of the intervention according to gender, age, marital status, number of years of exposure and time since last exposure to the intervention. METHODS: In 2007, a cross-sectional survey was conducted in the 20 trial communities among 13,814 young people (15-30 yrs) who had attended intervention or comparison schools between 1999 and 2002. Outcomes for which the intervention had an impact in 2001 or 2007 were included in this subgroup analysis. Data were analysed using cluster-level methods for stratified cluster-randomised trials, using interaction tests to determine if intervention impact differed by subgroup. RESULTS: Taking into account multiplicity of testing, concurrence with a priori hypotheses and consistency within the results no strong effect-modifiers emerged. Impact on pregnancy knowledge and reported attitudes to sex increased with years of exposure to high-quality intervention. CONCLUSIONS: The desirable long-term impact of the MEMA kwa Vijana intervention did not vary greatly according to the subgroups examined. This suggests that the intervention can have an impact on a broad cross-section of young people in rural Mwanza. TRIAL REGISTRATION: ClinicalTrials.gov NCT00248469

Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis (PRedSS)

From SAGE Publishing via Jisc Publications RouterHistory: received 2020-05-08, accepted 2020-08-16, epub 2020-09-17Publication status: PublishedFunder: Versus Arthritis; FundRef: https://doi.org/10.13039/501100012041; Grant(s): 21021Background:: Many of the painful, disabling features of early diffuse cutaneous systemic sclerosis have an inflammatory component and are potentially treatable with corticosteroid therapy. These features include painful and itchy skin, fatigue and musculoskeletal involvement. Yet many clinicians are understandably reluctant to prescribe corticosteroids because of the concern that these are a risk factor for scleroderma renal crisis. The aim of PRedSS (PRednisolone in early diffuse cutaneous Systemic Sclerosis) is to evaluate the efficacy and safety of moderate dose prednisolone in patients with early diffuse cutaneous systemic sclerosis, specifically whether moderate dose prednisolone is (a) effective in terms of reducing pain and disability, and improving skin score and (b) safe, with particular reference to renal function. Methods:: PRedSS is a Phase II, multicentre, double-blind randomised controlled trial which aims to recruit 72 patients with early diffuse cutaneous systemic sclerosis. Patients are randomised to receive either prednisolone (dosage approximately 0.3 mg/kg) or placebo therapy for 6 months. The two co-primary outcome measures are the difference in mean Health Assessment Questionnaire Disability Index at 3 months and the difference in modified Rodnan skin score at 3 months. Secondary outcome measures include patient reported outcome measures of itch, hand function, anxiety and depression, and helplessness. Results:: Recruitment commenced in December 2017 and after a slow start (due to delays in opening centres) 25 patients have now been recruited. Conclusion:: PRedSS should help to answer the question as to whether clinicians should or should not prescribe prednisolone in early diffuse cutaneous systemic sclerosis