World IVF Day: Let the Celebration Begin Onyewuenyi, Ticara L; Williamson, Elizabeth; Flyckt, Rebecca ...
Journal of obstetrics and gynaecology Canada,
07/2023, Letnik:
45, Številka:
7
Journal Article
These results from a 2014 phase 2 clinical trial in Panamanian infants suggest that high-dose inactivated polio vaccines (IPVs), like standard IPVs, are largely ineffective at inducing levels of ...intestinal immune responses requisite to control poliovirus shedding.
Abstract
Background
The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood.
Methods
In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2–specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants’ intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples.
Results
Despite mIPV2HD’s 4-fold higher type 2 polio D–antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants’ intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2–specific IgA responses and stool neutralization were observed by 2 weeks after challenge.
Conclusions
Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge.
Clinical Trials Registration
NCT02111135.
BACKGROUND:Measures of central pain processing like conditioned pain modulation and suprathreshold heat pain response (SHPR) have been described to assess different components of central pain ...modulatory mechanisms. Central pain processing potentially plays a role in the development of postsurgical pain, however, the role of conditioned pain modulation and SHPR in explaining postoperative clinical pain and disability is still unclear.
METHODS:Seventy-eight patients with clinical shoulder pain were included in this study. Patients were examined before shoulder surgery, at 3 months, and 6 months after surgery. The primary outcome measures were pain intensity and upper extremity disability.
RESULTS:Analyses revealed that the change score (baseline- 3 mo) of fifth pain rating of SHPR accounted for a significant amount of variance in 6-month postsurgical clinical pain intensity and disability after age, sex, preoperative pain intensity, and relevant psychological factors were considered.
CONCLUSIONS:The present study suggests that baseline measures of central pain processing were not predictive of 6-month postoperative pain outcome. Instead, the 3-month change in SHPR might be a relevant factor in the transition to an elevated 6-month postoperative pain and disability outcomes. In patients with shoulder pain, the 3-month change in a measure of central pain processing might be a relevant factor in the transition to elevated 6-month postoperative pain and disability scores.
We recently sought to integrate our orthopaedic and plastic hand surgeons with the goal of improving education, patient care, and providing seamless, continuous coverage for our trauma center. Our ...hypothesis was that integration could serve both the orthopaedic and plastic surgery training programs well and provide more consistent care for the trauma patients.
Program director approval was granted for blinded analysis of case logs from plastic and orthopaedic surgery programs from 2012 through 2019. Data on mean and total number of hand cases were analyzed and compared for both specialties. Institutional Review Board approval was granted for a retrospective review of patient outcomes.
For both orthopaedic and plastics resident trainees, the mean number of hand cases increased during this study period suggesting that the integration had a favorable impact on both programs. The mean number of hand cases for orthopaedic residents rose from 163 to 246. The mean number of hand cases for plastic surgery residents rose from 218 to 295. Patient outcomes as reflected in length of stay and time to consultation also improved.
To improve hand surgical training and patient care, an integrated orthoplastics approach to hand surgery was implemented at our institution. Plastic surgery trainees are completing more hand surgery cases in an integrated model (p < 0.001), including fracture care (p < 0.047). Orthopaedic surgery trainees have doubled the percentage of integumentary and microsurgery cases in the integrated model (p < 0.001). The educational and clinical changes affected in an integrated model have changed the paradigm for educating future hand surgeons at our institution.
Heterogeneous architectures are increasingly common in modern High-Performance Computing (HPC) systems. Achieving high-performance on such heterogeneous systems requires new approaches to application ...development that are able to achieve the three Ps: Performance, Portability, and Productivity.
In this paper, we provide an overview of the state-of-the-art for developing high-performance, portable and productive multi-physics applications with particular focus on the simulation of a plasma fusion reactor. Simulating such a complex system relies on both fluid- and particle-based simulations, and coupling interfaces between these two domains. We also review the current state-of-the-art in reasoning about the performance, portability and productivity of HPC applications.
•Outlines approaches to developing high-performance numerical simulations.•Reviews the state-of-the-art in programming languages and parallel programming models.•Summarises high- and low-level domain specific languages targeting plasma fusion.•Outlines methods for coupling scientific simulations.•Describes methods for reasoning about performance, portability and productivity in HPC.
Soybean rust is an economically significant disease caused by the fungus
that negatively impacts soybean (
(L.) Merr.) production throughout the world. Susceptible plants infected by
develop ...tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci (
to
) that provide race-specific resistance to
(
) have been identified.
was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two
genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the
locus to a 371 kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify
, we designed oligonucleotide primers to amplify
candidate (
) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five
genes were identified in both
-resistant soybean lines, and co-silencing these genes compromised resistance to
. Gene expression analysis and sequence comparisons of the
genes in PI 462312 and PI 506764 suggest that a single candidate gene,
, is responsible for
-mediated resistance.
This is a revision of the previous joint Policy Statement titled "Guidelines for Care of Children in the Emergency Department." Children have unique physical and psychosocial needs that are ...heightened in the setting of serious or life-threatening emergencies. The majority of children who are ill and injured are brought to community hospital emergency departments (EDs) by virtue of proximity. It is therefore imperative that all EDs have the appropriate resources (medications, equipment, policies, and education) and capable staff to provide effective emergency care for children. In this Policy Statement, we outline the resources necessary for EDs to stand ready to care for children of all ages. These recommendations are consistent with the recommendations of the Institute of Medicine (now called the National Academy of Medicine) in its report "The Future of Emergency Care in the US Health System." Although resources within emergency and trauma care systems vary locally, regionally, and nationally, it is essential that ED staff, administrators, and medical directors seek to meet or exceed these recommendations to ensure that high-quality emergency care is available for all children. These updated recommendations are intended to serve as a resource for clinical and administrative leadership in EDs as they strive to improve their readiness for children of all ages.
Macrophage stimulating protein (MSP) is a serum growth factor that binds to and activates the receptor tyrosine kinase, Recepteur d'Origine Nantais (RON). A non-synonymous coding variant in MSP ...(689C) has been associated with genetic susceptibility to both Crohn's disease and ulcerative colitis, two major types of inflammatory bowel disease (IBD) characterized by chronic inflammation of the digestive tract. We investigated the consequences of this polymorphism for MSP-RON pathway activity and IBD pathogenesis.
RON expression patterns were examined on mouse and human cells and tissues under normal and disease conditions to identify cell types regulated by MSP-RON. Recombinant MSP variants were tested for their ability to bind and stimulate RON and undergo proteolytic activation. MSP concentrations were quantified in the serum of individuals carrying the MSP 689R and 689C alleles.
In intestinal tissue, RON was primarily expressed by epithelial cells under normal and disease conditions. The 689C polymorphism had no impact on the ability of MSP to bind to or signal through RON. In a cohort of normal individuals and IBD patients, carriers of the 689C polymorphism had lower concentrations of MSP in their serum.
By reducing the quantities of circulating MSP, the 689C polymorphism, or a variant in linkage disequilibrium with this polymorphism, may impact RON ligand availability and thus receptor activity. Given the known functions of RON in regulating wound healing and our analysis of RON expression patterns in human intestinal tissue, these data suggest that decreased RON activity may impact the efficiency of epithelial repair and thus underlie the increased IBD susceptibility associated with the MSP 689C allele.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and ...3 immunotherapy clinical trials and clinical care. Additionally, investigational tools—including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents—offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles ...outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.
Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required.
Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals.
Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.