Clinician-Research Collaboration: Determining Research Interests and Needs of Clinicians in the Tri-Cities, TN

This research explores the disconnect between researchers and practicing clinicians on research collaboration, which is attributed to various barriers, therefore creating a researcher-clinician gap. Survey research was conducted and practicing clinicians in the Tri-Cities region of Tennessee acted as respondents. Results may contribute to establishing practicing clinician-research collaboration in this context

Young Adults with Cleft Lip and Palate: Personal Perspectives of Transition of Care

Children with cleft lip/palate receive team care which typically ends at eighteen. Young adults then need to transition into an adult-centered model of care. A paucity of literature exists regarding their perspective on transition of care experience. This research explores the experiences of young adults with CLP regarding their transition of care process, within the person-centered ICF framework

Barriers to managing childhood mental health problems: a systematic review of primary care practitioner's perceptions

Background: Mental health problems are common and typically have an early onset. Effective treatments for mental health problems in childhood and adolescence are available yet only a minority of affected children access them. This is of serious concern, considering the far-reaching and long-term negative consequences of such problems. Primary care is usually the first port of call for concerned parents so it is important to understand how primary care practitioners (PCPs) manage childhood mental health problems and the barriers they face. Aim: To ascertain PCP’s perceptions of barriers preventing effective management of childhood mental health problems Design: A systematic review of qualitative and quantitative literature Method: A database search of peer-reviewed articles using PsycInfo, MEDLINE, EMBASE and Web of Science, until October 2014, was conducted. Additional studies were identified through hand-searching and forward-citation searches. Studies needed to have at least one search term in four categories: (i) primary care, (ii) childhood/adolescence, (iii) mental health and (iv) barriers. Results: A total of 4151 articles were found, of which 43 were included (30 quantitative and 13 qualitative). The majority of the barriers related to identification, management and/or referral. Considerable barriers included a lack of providers and resources, extensive waiting lists and financial restrictions. Conclusion: The identification of a broad range of significant barriers highlights the need to strengthen the ability to deal with these common difficulties in primary care. There is a particular need for tools and training to aid accurate identification and management, and for more efficient access to specialist services

The druggable antimalarial target PfDXR : overproduction strategies and kinetic characterization

Plasmodium falciparum 1–deoxy–D–xylulose–5–phosphate reductoisomerase (PfDXR) is a key enzyme in the synthesis of isoprenoids in the malaria parasite, using a pathway that is absent in the human host. This enzyme is receiving attention as it has been validated as a promising drug target. However, an impediment to the characterisation of this enzyme has been the inability to obtain sufficient quantities of the enzyme in a soluble and functional form. The expression of PfDXR from the codon harmonised coding region, under conditions of strongly controlled transcription and induction, resulted in a yield of 2 – 4 mg/L of enzyme, which is 8 to 10–fold higher than previously reported yields. The kinetic parameters Km, Vmax and kcat were determined for PfDXR using an NADPH–dependent assay. Residues K295 and K297, unique to species of Plasmodium and located in the catalytic hatch region; and residues V114 and N115, essential for NADPH binding, were mutated to resemble those found in E. coli DXR. Interestingly, these mutations decreased the substrate affinity of PfDXR to values resembling that of E. coli DXR. PfDXR-K295N, K297S and PfDXR-V114A, N115G demonstrated a decreased ability to turnover substrate by 4–fold and 2-fold respectively in comparison to PfDXR. This study indicates a difference in the role of the catalytic hatch in capturing substrate by species of Plasmodium. The results of this study could contribute to the development of inhibitors of PfDXR.National Research Foundation Grant awarded to AB (Thuthuka Programme) and a SAMI Grant awarded to GLB. LSS was awarded a post–doctoral bursary by the South African Malaria Initiative programme; JG was awarded a PhD bursary by SAMI and National Research Foundation and HJ was awarded an Honours bursary by Rhodes University.http://www.eurekaselect.com/628/journal/protein-amp-peptide-lettershb201

Phenotypic diversity of circulating tumour cells in patients with metastatic castration‐resistant prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/1/bju13631_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/2/bju13631.pd

Allergic reactions to the Ad26.COV2.S vaccine in South Africa

BACKGROUND : The Janssen-Ad26.COV2.S vaccine is authorized for use in several countries, with more than 30 million doses administered. Mild and severe allergic adverse events following immunization (AEFI) have been reported. OBJECTIVE : We sought to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. METHODS : A single dose of the Ad26.COV2.S vaccine was administered to 4,77,234 South African health care workers between February 17 and May 17, 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy.” Anaphylaxis adjudication was performed using the Brighton Collaboration and National Institute of Allergy and Infectious Disease case definitions. RESULTS : Only 251 (0.052%) patients reported any allergic-type reaction (<1 in 2000), with 4 cases of adjudicated anaphylaxis (Brighton Collaboration level 1, n = 3) (prevalence of 8.4 per million doses). All anaphylaxis cases had a previous history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest nonanaphylatic reactions and included self-limiting, transient/localized rashes requiring no health care contact (n = 92) or isolated urticaria and/or angioedema (n = 70; median onset, 48 [interquartile range, 11.5-120] hours postvaccination) that necessitated health care contact (81%), antihistamine (63%), and/or systemic/topical corticosteroid (16%). All immediate (including adjudicated anaphylaxis) and most delayed AEFI (65 of 69) cases resolved completely. CONCLUSIONS : Allergic AEFI are rare following a single dose of Ad26.COV, with complete resolution in all cases of anaphylaxis. Although rare, isolated, delayed-onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.The Sinsonke Study is funded by the South African Medical Research Council. J.P.’s research is supported by a career development award and financial support from the National Institutes of Health; the European Developing Clinical Trials Partnership (EDCTP2 Program supported by the European Union; and the SA Medical Research Council and National Research Foundation.https://www.sciencedirect.com/journal/journal-of-allergy-and-clinical-immunology-globalhj2023Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

Measuring the Impact of Conservation : The Growing Importance of Monitoring Fauna, Flora and Funga

Many stakeholders, from governments to civil society to businesses, lack the data they need to make informed decisions on biodiversity, jeopardising efforts to conserve, restore and sustainably manage nature. Here we review the importance of enhancing biodiversity monitoring, assess the challenges involved and identify potential solutions. Capacity for biodiversity monitoring needs to be enhanced urgently, especially in poorer, high-biodiversity countries where data gaps are disproportionately high. Modern tools and technologies, including remote sensing, bioacoustics and environmental DNA, should be used at larger scales to fill taxonomic and geographic data gaps, especially in the tropics, in marine and freshwater biomes, and for plants, fungi and invertebrates. Stakeholders need to follow best monitoring practices, adopting appropriate indicators and using counterfactual approaches to measure and attribute outcomes and impacts. Data should be made openly and freely available. Companies need to invest in collecting the data required to enhance sustainability in their operations and supply chains. With governments soon to commit to the post-2020 global biodiversity framework, the time is right to make a concerted push on monitoring. However, action at scale is needed now if we are to enhance results-based management adequately to conserve the biodiversity and ecosystem services we all depend on.This paper was made possible by funding from the Swiss Network for International Studies to the University of Lausanne (L.F. and P.J.S.) and its partners under the project: "Unblocking the flow of biodiversity data for multi-stakeholder environmental sustainability management". The research was carried out, in part, by GNG at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). PAVB was supported by the project MACRISK-PTDC/BIA-CBI/0625/2021, through the FCT-FundacAo para a Ciencia e a Tecnologia. YNB acknowledges support from the Audemars-Watkins Foundation for the CBCR's protected area monitoring work featured in this paper.info:eu-repo/semantics/publishedVersio

Measuring the Impact of Conservation: The Growing Importance of Monitoring Fauna, Flora and Funga

Many stakeholders, from governments to civil society to businesses, lack the data they need to make informed decisions on biodiversity, jeopardising efforts to conserve, restore and sustainably manage nature. Here we review the importance of enhancing biodiversity monitoring, assess the challenges involved and identify potential solutions. Capacity for biodiversity monitoring needs to be enhanced urgently, especially in poorer, high-biodiversity countries where data gaps are disproportionately high. Modern tools and technologies, including remote sensing, bioacoustics and environmental DNA, should be used at larger scales to fill taxonomic and geographic data gaps, especially in the tropics, in marine and freshwater biomes, and for plants, fungi and invertebrates. Stakeholders need to follow best monitoring practices, adopting appropriate indicators and using counterfactual approaches to measure and attribute outcomes and impacts. Data should be made openly and freely available. Companies need to invest in collecting the data required to enhance sustainability in their operations and supply chains. With governments soon to commit to the post-2020 global biodiversity framework, the time is right to make a concerted push on monitoring. However, action at scale is needed now if we are to enhance results-based management adequately to conserve the biodiversity and ecosystem services we all depend on

千葉大学泌尿器科第1回同門会発表

BackgroundWhile programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity in a proportion of patients with advanced bladder cancer, strongly predictive and prognostic biomarkers are still lacking. In this study, we evaluated PD-L1 protein expression on circulating tumor cells (CTCs) isolated from patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer and explore the prognostic value of CTC PD-L1 expression on clinical outcomes.MethodsBlood samples from 25 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK)+ and (CK)-CTCs (CD45-, intact nuclei, morphologically distinct from WBCs) were enumerated. A subset of patient samples underwent genetic characterization by fluorescence in situ hybridization (FISH) and copy number variation (CNV) analysis.ResultsCTCs were detected in 20/25 (80 %) patients, inclusive of CK+ CTCs (13/25, 52 %), CK-CTCs (14/25, 56 %), CK+ CTC Clusters (6/25, 24 %), and apoptotic CTCs (13/25, 52 %). Seven of 25 (28 %) patients had PD-L1+ CTCs; 4 of these patients had exclusively CK-/CD45-/PD-L1+ CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH and CNV analysis, which revealed marked genomic instability. Although this study was not powered to evaluate survival, exploratory analyses demonstrated that patients with high PD-L1+/CD45-CTC burden and low burden of apoptotic CTCs had worse overall survival.ConclusionsCTCs are detectable in both MIBC and mBCa patients. PD-L1 expression is demonstrated in both CK+ and CK-CTCs in patients with mBCa, and genomic analysis of these cells supports their tumor origin. Here we demonstrate the ability to identify CTCs in patients with advanced bladder cancer through a minimally invasive process. This may have the potential to guide checkpoint inhibitor immune therapies that have been established to have activity, often with durable responses, in a proportion of these patients

Safety evaluation of the single-dose Ad26. COV2.S vaccine among healthcare workers in the Sisonke study in South Africa : a phase 3b implementation trial

Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data.Funding for the Sisonke Study was provided by: The National Department of Health through baseline funding to the South African Medical Research Council; the Solidarity Response Fund NPC; The Michael & Susan Dell Foundation; the ELMA Vaccines and Immunization Foundation; the ELMA Vaccines and Immunization Foundation; and the Bill & Melinda Gates Foundation.https://journals.plos.org/plosmedicinedm2022Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH