54 research outputs found
Effect of salt and temperature stresses on survival and infectivity of Heterorhabditis spp. IJs
Heterorhabditis is frequently found in coastal sandy soils where it may experience both high salinity and high temperatures. We tested the ability of infective juveniles (IJs) of three taxonomic groups of Heterorhabditis to infect insects in saline sand. We also tested whether salinity (sea water) affected the IJs' ability to tolerate elevated temperatures in aqueous suspension and in sand. IJs of all three taxonomic groups killed Galleria mellonella in saline sand (25.6% insects killed), but at a lower level than in non-saline sand (96.5% insects killed). Exposure of IJs in sand to high temperature reduced their ability to kill G. mellonella at 20 degrees C; heating IJs in saline sand reduced G. mellonella mortality to a lesser extent (25.6% at 20 degrees C, 18.3% at 39 degrees C) than heating in non-saline sand (96.5% at 20 degrees C, 17.5% at 39 degrees C). In aqueous suspension, IJs of the North-West European and Irish types of Heterorhabditis tolerated high temperature better in sea water (at least 95% survived 1 h at 39 C) than in distilled water (none survived 1 h at 38 degrees C). H. bacteriophora was more temperature tolerant: survival and subsequent infectivity of IJs was unaffected by temperature up to 39 degrees C in either medium. It was concluded that high salinity (sea water) reduces the ability of Heterorhabditis IJs to infect, but improves their tolerance of high temperature
Effect of salt and temperature stresses on survival and infectivity of Heterorhabditis spp. IJs
Heterorhabditis is frequently found in coastal sandy soils where it may experience both high salinity and high temperatures. We tested the ability of infective juveniles (IJs) of three taxonomic groups of Heterorhabditis to infect insects in saline sand. We also tested whether salinity (sea water) affected the IJs' ability to tolerate elevated temperatures in aqueous suspension and in sand. IJs of all three taxonomic groups killed Galleria mellonella in saline sand (25.6% insects killed), but at a lower level than in non-saline sand (96.5% insects killed). Exposure of IJs in sand to high temperature reduced their ability to kill G. mellonella at 20 degrees C; heating IJs in saline sand reduced G. mellonella mortality to a lesser extent (25.6% at 20 degrees C, 18.3% at 39 degrees C) than heating in non-saline sand (96.5% at 20 degrees C, 17.5% at 39 degrees C). In aqueous suspension, IJs of the North-West European and Irish types of Heterorhabditis tolerated high temperature better in sea water (at least 95% survived 1 h at 39 C) than in distilled water (none survived 1 h at 38 degrees C). H. bacteriophora was more temperature tolerant: survival and subsequent infectivity of IJs was unaffected by temperature up to 39 degrees C in either medium. It was concluded that high salinity (sea water) reduces the ability of Heterorhabditis IJs to infect, but improves their tolerance of high temperature
Knowledge translation and the power of the nursing academic conference
The national and international conference experiences present a unique learning opportunity. There are differing events that reflect the full nursing employment spectrum from clinical delivery, organizational and policy development and academia in education and research. Many conferences provide a platform for academics with differing levels of experience to come together and welcome contributions from students and all grades of post-registration nurses, educationalists, administrators, and researchers. In selecting the programme, the conference organisers will often circulate a calling notice and potential presenters will submit their abstracts to be blind peer reviewed. Therefore, conferences showcase the best of the best and provide the current perspective of areas of growth within the nursing sector. Conferences have a plethora of delivery routes ranging from posters, oral presentations (both short and long), panel discussions, key notes, seminars, exhibitions and workshops. These present an exceptional chance to listen, present, network and discuss nursing innovation and academic research
Where We Fall Down: Tensions in Teaching Social Medicine and Global Health
Background: As global health interest has risen, so too has the relevance of education on the social determinants of health and health equity. Social medicine offers a particularly salient framework for educating on the social determinants of health, health disparities, and health equity. SocMed and EqualHealth, 2 unique but related organizations, offer annual global health courses in Uganda, Haiti, and the United States, which train students to understand and respond to the social determinants of health through praxis, self-reflection and self-awareness, and building collaborative partnerships across difference. Objectives: The aim of this paper is to describe an innovative pedagogical approach to teaching social medicine 'and' global health. We draw on the notion of praxis, which illuminates the value of iterative reflection and action, to critically examine our points of weakness as educators in order to derive lessons with broad applicability for those engaged in global health work. Methods: The data for this paper were collected through an autoethnography of teaching 10 global health social medicine courses in Uganda and Haiti since 2010. It draws on revealing descriptions from participant observation, student feedback collected in anonymous course evaluations, and ongoing relationships with alumni. Findings: Critical analysis reveals 3 significant and complicated tensions raised by our courses. The first point of weakness pertains to issues of course ownership by North American outsiders. The second tension emerges from explicit acknowledgment of social and economic inequities among our students and faculty. Finally, there are ongoing challenges of sustaining positive momentum toward social change after transformative course experiences. Conclusions: Although successful in generating transformative learning experiences, these courses expose significant fracture points worth interrogating as educators, activists, and global health practitioners. Ultimately, we have identified a need for building equitable partnerships and intentional community, embracing discomfort, and moving beyond reflection to praxis in global health education
Specific Adherence of Sporangia of a Paenibacillus Sp. Bacterium to Heterorhabditis Spp. Nematodes. Hitching a Ride to Lunch?
The fact that entomopathogenic nematodes of the genera Heterorhabditis and Stemernema are
normally found in mutuahstic association with the bacteria Photorhabdus spp. and
Xenorhabdus spp , respectively, has long been universally accepted However, the extent and
nature of their interaction with bacteria other than these, under natural conditions, is less well
known. There have been a number of reports of other bacteria being isolated from
entomopathogenic nematodes, particularly from Stemernema spp. (reviewed by Boemare et
al, 1998a). Jackson et al (1995) reported the occurrence oĂ Providencia rettgeri with a
number of strains of Heterorhabditis spp. originating from different geographical regions.
Boemare et al (1998b) point out that Ă©cologiste will tend to harvest nematodes resulting from
"successful" parasitisms, i e. those where the cadaver is not more rapidly putrefied by the
presence of co-associated bacteria other that the natural symbiont. With this in mind it is
conceivable that we may under-estimate the frequency of association of these nematodes with
other bacteria
Long-Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52-Week Extension Trial.
OBJECTIVE: To evaluate the long-term safety and tolerability of ubrogepant for the acute treatment of migraine.
BACKGROUND: Ubrogepant is an oral, calcitonin gene-related receptor antagonist in development for the acute treatment of migraine. The efficacy of ubrogepant was demonstrated in 2 phase 3 trials in which a significant improvement was observed in migraine headache pain, migraine-associated symptoms, and ability to function.
METHODS: This was a phase 3, multicenter, randomized, open-label, 52-week extension trial. Adults with migraine with or without aura entered the trial after completing one of 2 phase 3 lead-in trials and were re-randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg. Randomization to ubrogepant dose was blinded. Those randomized to usual care continued to treat migraine attacks with their own medication. The usual care arm was included in this trial to capture background rates of hepatic laboratory parameters and contextualize hepatic safety assessments. Safety and tolerability were the primary outcome measures. The safety population for the ubrogepant arms included all randomized participants who received at least 1 dose of treatment. All cases of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations of â„3 times the upper limit of normal were adjudicated by an independent panel of liver experts who were blinded to dose.
RESULTS: The safety population included 1230 participants (404 in the ubrogepant 50-mg group, 409 in the ubrogepant 100-mg group, and 417 in the usual care group). Participants were on average 42 years of age, 90% (1106/1230) female and 85% (1043/1230) white, with an average BMI of 30 kg/m
CONCLUSIONS: Long-term intermittent use of ubrogepant 50 and 100 mg given as 1 or 2 doses per attack for the acute treatment of migraine was safe and well tolerated, as indicated by a low incidence of treatment-related TEAEs and SAEs and discontinuations due to adverse events in this 1-year trial
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Protein hydrolysates from quinoa (Chenopodium quinoa Willd.) modulate macrophage polarization and the expression of surface antigen molecules
Quinoa (Chenopodium quinoa Willd.) is considered an exceptional source of highâquality protein and may be a good precursor of bioactive components with immunomodulatory effects. Quinoa proteinâenriched fraction (QPF) was isolated from quinoa seeds via alkaline extraction and isoelectric point precipitation and hydrolyzed at the optimum temperature and pH of two foodâgrade proteases to produce QPF hydrolysates (QPFH). SDSâPAGE and LCâMS analyses showed that lowâmolecular weight peptides were present in hydrolyzed proteins and that the enzymes effectively hydrolyzed highâmolecular weight proteins evidenced by significantly higher amino acid levels in QPFH. J774A.1 macrophages and mouse boneâmarrowâderived macrophages (BMDMs) were polarized into an M1âlike (proâinflammatory) or M2âlike (antiâinflammatory) state in the absence or presence of QPF or QPFH. Our results showed that QPFH attenuated M1âlike response as demonstrated by a significantly lowered secretion of proâinflammatory cytokines (ILâ6, TNFâα, ILâ12p40, and ILâ27p28) and nitric oxide (NO) levels. Coâtreatment with QPFH significantly boosted ILâ10 and arginase activity in both M1âlike and M2âlike cells indicating that the samples may promote a phenotypic switch to M2âlike macrophages. Furthermore, QPFH inhibited proâinflammatory cytokines in Loxoribine (LOX)âactivated bone marrowâderived dendritic cells (BMDCs) and inhibited the same cytokines during a 7âdayâDC maturation experiment. QPF but not the QPFH influenced the expression of surface antigen molecules in macrophages by decreasing the frequency of MHCI and CD86 expressing cells. Taken together, these findings reveal novel mechanisms that demonstrate the potential of quinoa protein hydrolysates in the development of immunomodulatory functional foods
Sustained Response to Atogepant in Episodic Migraine: Post Hoc Analyses of a 12-Week Randomized Trial and a 52-Week Long-Term Safety Trial
BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.
METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as â„50%, â„75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated.
RESULTS: In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8-81.1% following an initial â„50% response, 47.3-61.9% following an initial â„75% response, and 34.8-41.7% following an initial 100% response. Of those who experienced an initial â„75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial â„50% response, 72.6% following an initial â„75% response, and 37.8% following an initial 100% response. Of those who experienced an initial â„75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4.
CONCLUSION: Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018)
Safety and Tolerability Results of Atogepant for the Preventive Treatment of Episodic Migraine From a 40-Week, Open-Label Multicenter Extension of the Phase 3 ADVANCE Trial
Background: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059).
Methods: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period.
Results: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at â„3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at \u3e0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each).
Conclusion: These results are consistent with atogepant\u27s known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312
Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total nâ=â1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2â=â0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF)â=â31.1% in SLE cases compared with 22.5% in controls (ORâ=â1.56, pâ=â10â16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAFâ=â35.1%, ORâ=â1.86, p<10â19), nephritis (MAFâ=â34.3%, ORâ=â1.80, p<10â11), and age at diagnosis<30 years (MAFâ=â33.8%, ORâ=â1.77, p<10â13). An association with severe nephritis was even more striking (MAFâ=â39.2%, ORâ=â2.35, p<10â4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease
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