Publications by authors named "R Stephen Smith"

21,178 Publications

  • Page 1 of 1

HIRA contributes to zygote formation in mice and is implicated in human 1PN zygote phenotype.

Reproduction 2021 Apr 1. Epub 2021 Apr 1.

C Lin, Centre for Reproductive Health, The University of Edinburgh MRC Centre for Reproductive Health, Edinburgh, United Kingdom of Great Britain and Northern Ireland.

Elucidating the mechanisms underpinning fertilisation is essential to optimising IVF procedures. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. HIRA is the main H3.3 chaperone governing this protamine-to-histone exchange. Failure of this step results in abnormally fertilised zygotes containing only 1 pronucleus (1PN), in contrast to normal two-pronuclei (2PN) zygotes. 1PN zygotes are frequently observed in IVF treatments, but the genotype-phenotype correlation remains elusive. We investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1, in mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed an abnormal 1PN zygote phenotype. We then studied human 1PN zygotes and found that the HIRA complex was absent in 1PN zygotes that lacked the male pronucleus. This shows that the role of the HIRA complex in male pronucleus formation potentially has coherence from mice to humans. Furthermore, rescue experiments in mouse showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of HIRA. We have demonstrated that HIRA complex regulates male pronucleus formation in mice and is implicated in humans, that both CABIN1 and UBN1 components of the HIRA complex are equally essential for male pronucleus formation, and that rescue is feasible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/REP-20-0636DOI Listing
April 2021

Paid platelet donors: Points to consider.

Transfusion 2021 Apr;61(4):1000-1003

American Red Cross, Biomedical Services Headquarters, Washington, District of Columbia, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16329DOI Listing
April 2021

Simvastatin loaded chitosan guided bone regeneration membranes stimulate bone healing.

J Periodontal Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Biomedical Engineering, University of Memphis, Memphis, TN, USA.

Background And Objective: Electrospun chitosan membranes (ESCM) modified with short-chain fatty acids have the ability to control the release of simvastatin (SMV), an anti-cholesterol drug with osteogenic potential, for guided bone regeneration (GBR) applications. This study evaluated in vivo osteogenic effects of rapid short release of SMV (4 weeks) vs long sustained release (8 weeks) from acetic anhydride (AA)-and hexanoic anhydride (HA)-modified ESCMs, respectively.

Methods: AA ESCMs loaded with 10 or 50 µg SMV and HA ESCMs loaded with 50 µg SMV were evaluated for biocompatibility and bone formation at 4 and 8 weeks, in 5 mm critical size rat calvarial defects, using histological evaluation and micro-CT analysis.

Results: No severe inflammatory response was noticed around the ESCMs. Less hydrophobic AA membranes showed signs of resorption by week 4 and were almost completely resorbed by week 8 whereas the more hydrophobic HA membranes resorbed slowly, remaining intact over 8 weeks. In micro-CT analysis, 10 µg SMV-loaded AA membranes did not show significant bone formation as compared to non-loaded AA membranes at either evaluation time points. 50 µg SMV-loaded AA membranes stimulated significantly more bone formation than non-loaded AA membranes by week 4 (%bone = 31.0 ± 5.9% (AA50) vs 18.5 ± 13.7% (AA0)) but showed no difference at week 8. HA membranes with 50 µg SMV showed significantly more bone formation as compared to corresponding non-loaded membranes by week 8 (%bone = 61.7 ± 8.9% (HA50) vs 33.9 ± 29.7% (HA0)), though such an effect was not significant at week 4.

Conclusion: These results indicate that modified ESCMs may be used to control the release of SMV and promote bone healing in GBR applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jre.12883DOI Listing
April 2021

Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic.

J Child Neurol 2021 Apr 8:8830738211001209. Epub 2021 Apr 8.

Simons Foundation, New York, NY, USA.

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers' reported impact on their dependent's services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported "feeling stressed but able to deal with problems as they arise," and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08830738211001209DOI Listing
April 2021

An imaging refractometer for density fluctuation measurements in high energy density plasmas.

Rev Sci Instrum 2021 Mar;92(3):033521

Blackett Laboratory, Imperial College, London SW7 2AZ, United Kingdom.

We report on a recently developed laser-probing diagnostic, which allows direct measurements of ray-deflection angles in one axis while retaining imaging capabilities in the other axis. This allows us to measure the spectrum of angular deflections from a laser beam, which passes through a turbulent high-energy-density plasma. This spectrum contains information about the density fluctuations within the plasma, which deflect the probing laser over a range of angles. We create synthetic diagnostics using ray-tracing to compare this new diagnostic with standard shadowgraphy and schlieren imaging approaches, which demonstrates the enhanced sensitivity of this new diagnostic over standard techniques. We present experimental data from turbulence behind a reverse shock in a plasma and demonstrate that this technique can measure angular deflections between 0.06 and 34 mrad, corresponding to a dynamic range of over 500.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0040919DOI Listing
March 2021

The histone modification H3K4me3 is altered at the locus in Alzheimer's disease brain.

Future Sci OA 2021 Feb 9;7(4):FSO665. Epub 2021 Feb 9.

University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.

Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n = 59) or low (n = 29) Alzheimer's disease pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2144/fsoa-2020-0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015672PMC
February 2021

Knowing when to talk? Plant genome editing as a site for pre-engagement institutional reflexivity.

Public Underst Sci 2021 Apr 3:963662521999796. Epub 2021 Apr 3.

UK Research and Innovation, UK.

Citizen and stakeholder engagement is frequently portrayed as vital for socially accountable science policy but there is a growing understanding of how institutional dynamics shape engagement exercises in ways that prevent them from realising their full potential. Limited attention has been devoted to developing the means to expose institutional features, allow policy-makers to reflect on how they will shape engagement and respond appropriately. Here, therefore, we develop and test a methodological framework to facilitate pre-engagement institutional reflexivity with one of the United Kingdom's eminent science organisations as it grappled with a new, high-profile and politicised technology, genome editing. We show how this approach allowed policy-makers to reflect on their institutional position and enrich decision-making at a time when they faced pressure to legitimate decisions with engagement. Further descriptions of such pre-engagement institutional reflexivity are needed to better bridge theory and practice in the social studies of science.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963662521999796DOI Listing
April 2021

Tube-load model: A clinically applicable pulse contour analysis method for estimation of cardiac stroke volume.

Comput Methods Programs Biomed 2021 Mar 26;204:106062. Epub 2021 Mar 26.

Department of Mechanical Engineering, University of Canterbury, New Zealand.

Background And Objectives: Accurate, reproducible, and reliable real-time clinical measurement of stroke volume (SV) is challenging. To accurately estimate arterial mechanics and SV by pulse contour analysis, accounting for wave reflection, such as by a tube-load model, is potentially important. This study tests for the first time whether a dynamically identified tube-load model, given a single peripheral arterial input signal and pulse transit time (PTT), provides accurate SV estimates during hemodynamic instability.

Methods: The model is tested for 5 pigs during hemodynamic interventions, using either an aortic flow probe or admittance catheter for a validation SV measure. Performance is assessed using Bland-Altman and polar plot analysis for a series of long-term state-change and short-term dynamic events.

Results: The overall median bias and limits of agreement (2.5th, 97.5th percentile) from Bland-Altman analysis were -10% [-49, 36], and -1% [-28,20] for state-change and dynamic events, respectively. The angular limit of agreement (maximum of 2.5th, 97.5th percentile) from polar-plot analysis for state-change and dynamic interventions was 35.6, and 35.2, respectively.

Conclusion: SV estimation agreement and trending performance was reasonable given the severity of the interventions. This simple yet robust method has potential to track SV within acceptable limits during hemodynamic instability in critically ill patients, provided a sufficiently accurate PTT measure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmpb.2021.106062DOI Listing
March 2021

N-3 Polyunsaturated fatty acid ethyl esters decrease the invasion, but not the proliferation, of human colorectal cancer cells via a PI3K-dependent mechanism in vitro.

Prostaglandins Leukot Essent Fatty Acids 2021 Mar 24;167:102273. Epub 2021 Mar 24.

Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, 601 University Dr., San Marcos, TX, USA, 78666. Electronic address:

N-3 polyunsaturated fatty acid (PUFA) ethyl esters have been approved by the FDA for the treatment of dyslipidemia and are promising cancer therapeutics. The study objectives were to determine if and how n-3 PUFA ethyl esters affected the proliferation and invasion of colorectal cancer cells. SW620 and HCT-116 parental and HCT-116 mutant cells isogenic for constitutively active PI3K were treated with free or ethyl esterified n-3 PUFAs and counted 72 h later. Cells were also administered n-3 PUFA ethyl esters to determine if these compounds decreased invasion through Boyden chambers and PI3K activity via western blot analysis of phosphorylated Akt. Free and n-3 PUFA ethyl esters decreased the proliferation of all cell lines. The invasion and Akt phosphorylation of both parental cell lines was decreased following treatment but this did not occur in mutant cells. The ability of n-3 PUFA ethyl esters to decrease proliferation and invasion in vitro indicates these compounds may be effective in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plefa.2021.102273DOI Listing
March 2021

Eltrombopag Improves Erythroid Differentiation in a Human Induced Pluripotent Stem Cell Model of Diamond Blackfan Anemia.

Cells 2021 Mar 26;10(4). Epub 2021 Mar 26.

Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Diamond Blackfan Anemia (DBA) is a congenital macrocytic anemia associated with ribosomal protein haploinsufficiency. Ribosomal dysfunction delays globin synthesis, resulting in excess toxic free heme in erythroid progenitors, early differentiation arrest, and pure red cell aplasia. In this study, DBA induced pluripotent stem cell (iPSC) lines were generated from blood mononuclear cells of DBA patients with inactivating mutations in RPS19 and subjected to hematopoietic differentiation to model disease phenotypes. In vitro differentiated hematopoietic cells were used to investigate whether eltrombopag, an FDA-approved mimetic of thrombopoietin with robust intracellular iron chelating properties, could rescue erythropoiesis in DBA by restricting the labile iron pool (LIP) derived from excessive free heme. DBA iPSCs exhibited RPS19 haploinsufficiency, reduction in the 40S/60S ribosomal subunit ratio and early erythroid differentiation arrest in the absence of eltrombopag, compared to control isogenic iPSCs established by CRISPR/Cas9-mediated correction of the RPS19 point mutation. Notably, differentiation of DBA iPSCs in the presence of eltrombopag markedly improved erythroid maturation. Consistent with a molecular mechanism based on intracellular iron chelation, we observed that deferasirox, a clinically licensed iron chelator able to permeate into cells, also enhanced erythropoiesis in our DBA iPSC model. In contrast, erythroid maturation did not improve substantially in DBA iPSC differentiation cultures supplemented with deferoxamine, a clinically available iron chelator that poorly accesses LIP within cellular compartments. These findings identify eltrombopag as a promising new therapeutic to improve anemia in DBA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10040734DOI Listing
March 2021

Virtual Reality Warm-up Before Robot-assisted Surgery: A Randomized Controlled Trial.

J Surg Res 2021 Mar 30;264:107-116. Epub 2021 Mar 30.

University of Washington, Department of Urology, Seattle, Washington.

Trial Design: This was a randomized controlled trial.

Background: Intraoperative errors correlate with surgeon skill and skill declines with intervals of inactivity. The goals of this research were to identify the optimal virtual reality (VR) warm-up curriculum to prime a surgeon's technical skill and validate benefit in the operating room.

Materials And Methods: Surgeons were randomized to receive six trial sessions of a designated set of VR modules on the da Vinci Skills Simulator to identify optimal VR warm-up curricula to prime technical skill. After performing their curricula, warm-up effect was assessed based on performance on a criterion task. The optimal warm-up curriculum was chosen from the group with the best task time and video review-based technical skill. Robot-assisted surgery-experienced surgeons were then recruited to either receive or not receive warm-up before surgery. Skill in the first 15 min of surgery was assessed by blinded surgeon and crowdworker review as well as tool motion metrics. The intervention was performing VR warm-up before human robot-assisted surgery. Warm-up effect was measured using objective performance metrics and video review using the Global Evaluative Assessment of Robotic Skills tool. Linear mixed effects models with a random intercept for each surgeon and nonparametric modified Friedman tests were used for analysis.

Results: The group performing only a Running Suture task on the simulator was on average 31.3 s faster than groups performing other simulation tasks and had the highest Global Evaluative Assessment of Robotic Skills scores from 41 surgeons who participated. This was chosen as the optimal curriculum. Thereafter, 34 surgeons completed 347 surgeries with corresponding video and tool motion data. No statistically significant differences in skill were observed with the warm-up intervention.

Conclusions: We conclude that a robotic VR warm-up before performing the early stages of surgery does not impact the technical skill of the surgeon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2021.01.037DOI Listing
March 2021

Validation of the Injured Trauma Survivor Screen (ITSS): An AAST Multi-Institutional Trial.

J Trauma Acute Care Surg 2021 Mar 26. Epub 2021 Mar 26.

Milwaukee VA Medical Center Mental Health Division Medical College of Wisconsin Department of Surgery Medical College of Wisconsin Department of Surgery Medical College of Wisconsin Department of Surgery Virginia Commonwealth University Department of Psychiatry Virginia Commonwealth University Department of Psychiatry Emory University School of Medicine Department of Surgery Oregon Health & Science University Department of Surgery Oregon Health & Science University Department of Surgery Medical College of Wisconsin Comprehensive Injury Center Medical College of Wisconsin Department of Surgery Oregon Health & Science University Department of Surgery Medical College of Wisconsin Department of Surgery Medical College of Wisconsin Department of Surgery

Background: Psychological distress is common following a traumatic injury event. The Injured Trauma Survivor Screen (ITSS) was developed at a Level 1 trauma center to assess for posttraumatic stress disorder (PTSD) and major depressive episode (MDE) following admission for a traumatic injury. The ITSS sensitivity and specificity were analyzed 1-3 and 6-9 months post-injury to test the validity across trauma centers.

Method: Four Level 1 trauma centers from the East, Midwest, South and West in the United States recruited 375 eligible adult inpatients. (Excluded participants included those with moderate or severe TBI, whose injury was self-inflicted, were non-communicative, or were non-English speaking.) Baseline sample (63.2% White/Caucasian, 62.4% male, mean age = 45 (17.11) years, 42.4% injured by motor vehicle collision) measurements were conducted during index hospitalization. At first follow-up, 69.6% (N = 261) were retained; at second follow-up, 61.3% (N = 230) were retained. Measurements included the ITSS, PTSD Checklist for DSM-5 (PCL-5), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and Clinician-Administered PTSD Scaled for DSM 5 (CAPS-5).

Results: At follow-up 1 the ITSS PTSD subscale had a sensitivity of 75% and specificity of 78.8% and the MDE subscale had a sensitivity of 80.4% and specificity 65.6%. At follow-up two, the PTSD subscale had a sensitivity of 72.7% and specificity of 83.1% and the MDE subscale had a sensitivity of 76.1% and specificity 68.3%. A combined risk group using two symptom based measures administered at baseline produced increased specificity.

Conclusions: The 9-item ITSS continues to be an efficient and effective risk screen for PTSD and MDE following traumatic injury requiring hospitalization. This multi-institutional validation study creates a solid foundation for further exploration of the generalizability of this screen's psychometric properties in distinct populations.Prognostic Study, Evidence Level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000003079DOI Listing
March 2021

Outcomes of an interprofessional SBIRT training program: Knowledge attainment and perceived competence for practice.

Subst Abus 2021 Apr 2:1-9. Epub 2021 Apr 2.

College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

Background: One way to address substance misuse is to train health professional students in Screening, Brief Intervention, and Referral to Treatment (SBIRT), an early intervention strategy. This study evaluated a semester-long, 50-hour elective SBIRT training that blended online coursework with interprofessional experiences. Medicine, nursing, pharmacy, and social work students completed an interprofessional standardized patient experience and completed a minimum of two interprofessional SBIRT experiences at community agencies. We analyzed longitudinal data from 197 students using structural equation modeling to examine gains in knowledge and perceived competence, as well as to test if background variables predicted 30-day application of SBIRT knowledge and skills, 30-day satisfaction' 12-month frequencies of care for performing SBIRT; and number of SBIRT clients/patients served directly. Overall, student SBIRT knowledge and perceived competence both increased by more than a standard deviation during the course. Students who experienced larger gains in perceived competence rated the course significantly higher in terms of relevance and usefulness and, in turn, served significantly more SBIRT clients/patients during the following year. We did not find evidence that intra-individual growth in knowledge impacted the degree to which students ultimately applied SBIRT components. Finally, students who had more previous training and experience related to substance abuse ultimately reported greater application of SBIRT knowledge and skills. Interprofessional differences included: At baseline, medicine students had significantly lower substance abuse education knowledge as compared to the other disciplines. Pharmacy and social work students were more likely to have had previous experience with motivational interviewing. Baseline perceived competence in applying SBIRT was higher in social work and nursing. Upon completion, pharmacy and medicine students had lower satisfaction with the course. These findings suggest that SBIRT courses can increase knowledge and perceived competence; moreover, student background characteristics, work settings, and experiences may have important effects on learning SBIRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08897077.2021.1900982DOI Listing
April 2021

Evaluation of the CYP2D6 haplotype activity scores based on metabolic ratios of 4,700 patients treated with three different CYP2D6 substrates.

Clin Pharmacol Ther 2021 Mar 31. Epub 2021 Mar 31.

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, Stockholm, Sweden.

The metabolic activity of the polymorphic CYP2D6 enzyme is dependent on the CYP2D6 genotype; however, the guidelines for translating the genotype into phenotype, which are of relevance for adequate drug dose personalization, are ambiguous. In the present study, retrospective therapeutic drug monitoring data from 4,700 CYP2D6 genotyped patients treated with risperidone, venlafaxine, and/or aripiprazole were analyzed to quantify the effect of CYP2D6 genotype on the CYP2D6 metabolic activities, as measured by metabolic ratios of these substrates. The patients were categorized into diplotypes based on the presence of normal function (CYP2D6Norm), nonfunctional (CYP2D6Nonf) and decreased function (CYP2D6Decr i.e. CYP2D6*9, CYP2D6*10, and CYP2D6*41) CYP2D6 haplotypes. Significant correlations between the metabolic ratios were observed in patients (n=77-103) co-treated with risperidone and venlafaxine, risperidone and aripiprazole, or venlafaxine and aripiprazole (ρ = 0.874, 0.785, and 0.644, respectively; p<0.001 for all). Relative metabolic CYP2D6 diplotype activity was calculated based on that the metabolic ratios, where median values for CYP2D6Nonf/Nonf and CYP2D6Norm/Norm subgroups were set to 0% and 100%, respectively. The relative CYP2D6 activities were: 7.0% for CYP2D6Nonf/*41, 16.7% for CYP2D6Nonf/*9-10, 13.2% for CYP2D6*41/*41, 24.9% for CYP2D6*41/*9-10, 33.1% for CYP2D6*9-10/*9-10, 41.3% for CYP2D6Nonf/Norm, 55.0% for CYP2D6*41/Norm, 58.9% for CYP2D6*9-10/Norm, and 149.2% for CYP2D6Norm/Normx2. Compared to the CYP2D6Norm alleles, the activity scores of CYP2D6*41 and CYP2D6*9-10 alleles were estimated to be one sixth and one third, respectively. The results of this highly powered study provide a solid basis for the translation of the CYP2D6 genotype into a drug metabolic phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpt.2246DOI Listing
March 2021

Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

What Is Already Known About This Topic?: Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period.

What Is Added By This Report?: We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency.

What Are The Implications For Public Health Practice?: RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.03.19.21253964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010751PMC
March 2021

Hyperspectral autofluorescence characterization of drusen and sub-RPE deposits in age-related macular degeneration.

Ann Eye Sci 2021 Mar 15;6. Epub 2021 Mar 15.

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Soft drusen and basal linear deposit (BLinD) are two forms of the same extracellular lipid rich material that together make up an Oil Spill on Bruch's membrane (BrM). Drusen are focal and can be recognized clinically. In contrast BLinD is thin and diffusely distributed, and invisible clinically, even on highest resolution OCT, but has been detected on hyperspectral autofluorescence (AF) imaging . We sought to optimize histologic hyperspectral AF imaging and image analysis for recognition of drusen and sub-RPE deposits (including BLinD and basal laminar deposit), for potential clinical application.

Methods: Twenty locations specifically with drusen and 12 additional locations specifically from fovea, perifovea and mid-periphery from RPE/BrM flatmounts from 4 AMD donors underwent hyperspectral AF imaging with 4 excitation wavelengths (λ 436, 450, 480 and 505 nm), and the resulting image cubes were simultaneously decomposed with our published non-negative matrix factorization (NMF). Rank 4 recovery of 4 emission spectra was chosen for each excitation wavelength.

Results: A composite emission spectrum, sensitive and specific for drusen and presumed sub-RPE deposits (the SDr spectrum) was recovered with peak at 510-520 nm in all tissues with drusen, with greatest amplitudes at excitations λ 436, 450 and 480 nm. The RPE spectra of combined sources Lipofuscin (LF)/Melanolipofuscin (MLF) were of comparable amplitude and consistently recapitulated the spectra S1, S2 and S3 previously reported from all tissues: tissues with drusen, foveal and extra-foveal locations.

Conclusions: A clinical hyperspectral AF camera, with properly chosen excitation wavelengths in the blue range and a hyperspectral AF detector, should be capable of detecting and quantifying drusen and sub-RPE deposits, the earliest known lesions of AMD, before any other currently available imaging modality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/aes-20-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009528PMC
March 2021

Additional Feeding Reveals Differences in Immune Recognition and Growth of Parasites in the Mosquito Host.

mSphere 2021 03 31;6(2). Epub 2021 Mar 31.

Department of Entomology, Iowa State University, Ames, Iowa, USA

Mosquitoes may feed multiple times during their life span in addition to those times needed to acquire and transmit malaria. To determine the impact of subsequent blood feeding on parasite development in , we examined parasite infection with or without an additional noninfected blood meal. We found that an additional blood meal significantly reduced immature oocyst numbers, yet had no effect on the human parasite These observations were reproduced when mosquitoes were fed an artificial protein meal, suggesting that parasite losses are independent of blood ingestion. We found that feeding with either a blood or protein meal compromises midgut basal lamina integrity as a result of the physical distention of the midgut, enabling the recognition and lysis of immature oocysts by mosquito complement. Moreover, we demonstrate that additional feeding promotes oocyst growth, suggesting that human malaria parasites exploit host resources provided with blood feeding to accelerate their growth. This is in contrast to experiments with , where the size of surviving oocysts is independent of an additional blood meal. Together, these data demonstrate distinct differences in species in evading immune detection and utilizing host resources at the oocyst stage, representing an additional, yet unexplored component of vectorial capacity that has important implications for the transmission of malaria. Mosquitoes must blood feed multiple times to acquire and transmit malaria. However, the impact of an additional mosquito blood meal following malaria parasite infection has not been closely examined. Here, we demonstrate that additional feeding affects mosquito vector competence; namely, additional feeding significantly limits infection, yet has no effect on infection of the human parasite Our experiments support that these killing responses are mediated by the physical distension of the midgut and by temporary damage to the midgut basal lamina that exposes immature oocysts to mosquito complement, while human malaria parasites are able to evade these killing mechanisms. In addition, we provide evidence that additional feeding promotes oocyst growth. This is in contrast to , where oocyst size is independent of an additional blood meal. This suggests that human malaria parasites are able to exploit host resources provided by an additional feeding to accelerate their growth. In summary, our data highlight distinct differences in malaria parasite species in evading immune recognition and adapting to mosquito blood feeding. These observations have important, yet previously unexplored, implications for the impact of multiple blood meals on the transmission of malaria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSphere.00136-21DOI Listing
March 2021

Social determinants of COVID-19 incidence and outcomes: A rapid review.

PLoS One 2021 31;16(3):e0248336. Epub 2021 Mar 31.

Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.

Early reports indicate that the social determinants of health are implicated in COVID-19 incidence and outcomes. To inform the ongoing response to the pandemic, we conducted a rapid review of peer-reviewed studies to examine the social determinants of COVID-19. We searched Ovid MEDLINE, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from December 1, 2019 to April 27, 2020. We also searched the bibliographies of included studies, COVID-19 evidence repositories and living evidence maps, and consulted with expert colleagues internationally. We included studies identified through these supplementary sources up to June 25, 2020. We included English-language peer-reviewed quantitative studies that used primary data to describe the social determinants of COVID-19 incidence, clinical presentation, health service use and outcomes in adults with a confirmed or presumptive diagnosis of COVID-19. Two reviewers extracted data and conducted quality assessment, confirmed by a third reviewer. Forty-two studies met inclusion criteria. The strongest evidence was from three large observational studies that found associations between race or ethnicity and socioeconomic deprivation and increased likelihood of COVID-19 incidence and subsequent hospitalization. Limited evidence was available on other key determinants, including occupation, educational attainment, housing status and food security. Assessing associations between sociodemographic factors and COVID-19 was limited by small samples, descriptive study designs, and the timeframe of our search. Systematic reviews of literature published subsequently are required to fully understand the magnitude of any effects and predictive utility of sociodemographic factors related to COVID-19 incidence and outcomes. PROSPERO: CRD4202017813.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248336PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011781PMC
April 2021

Growing Neonatal Advanced Practice Providers via Mentorship Can Fill the Need: Program Description and Tool Kit.

Adv Neonatal Care 2021 Mar 25. Epub 2021 Mar 25.

Seattle Children's Hospital, Seattle, Washington.

Background: The need for neonatal advanced practice providers (APPs) has been described. Hospital training programs for neonatal physician assistants (PAs) have been developed by physicians. No publications exist about programs administered by neonatal APPs for both new graduate neonatal nurse practitioners (NNPs) and neonatal PAs.

Purpose: The purpose of this work was to mentor, train, and hire neonatal APPs in a program administered by neonatal APPs.

Methods: We developed a 2-pronged approach to attract PAs and new graduate NNPs. Marketing strategies included receptions, information, and mentorship. A 12-month neonatal PA fellowship program included clinical mentorship and weekly didactics. Case-based presentations were provided by neonatal APPs, neonatologists, and allied professionals. The new graduate NNP program included clinical mentorship and monthly meetings with peer support, lectures, and case presentations. Neonatal APPs were clinical mentors. Team-building activities supported mentorship and collaboration among all care providers.

Findings: In less than 5 years, 10 PAs and 11 new graduate NNPs have been trained and hired, as well as experienced neonatal APPs hired for this regional neonatology program. For the first time in years, locum tenens neonatal APPs are not required. We have developed a "tool kit" of content, activities, exercises, and evaluations to support successful attainment of expected competencies.

Implication For Research: Future studies can measure retention, satisfaction, and clinical outcomes.

Implication For Practice: A successful training program has been implemented to meet the growing demand. We support the values of integrity, collaboration, and equity to facilitate this successful paradigm shift among all neonatal professional team members.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ANC.0000000000000847DOI Listing
March 2021

Use of Predictive Modeling to Tailor Molecular Testing Utilization for Thyroid Nodules.

Otolaryngol Head Neck Surg 2021 Mar 30:1945998211004155. Epub 2021 Mar 30.

Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA.

Objective: Various risk stratification systems for cytologically indeterminate thyroid nodules are available. However, malignancy risk assessment data, such as ultrasound features, are not always used when the decision is to order molecular testing or not. Our aim was to investigate the utility of molecular testing after incorporating an algorithm with ultrasound-based risk of malignancy (ROM) estimation.

Study Design: Diagnostic/prognostic study.

Setting: Single-institution urban tertiary care center.

Methods: We performed a single-institution retrospective chart review of all thyroid nodules that had undergone molecular testing. A web-based Malignancy Risk Estimation System for Thyroid Nodules was utilized with ultrasound findings to stratify malignancy risk according to the Korean Thyroid Imaging Reporting and Data System (TI-RADS), French TI-RADS, American Association of Clinical Endocrinology guideline, and American Thyroid Association guideline. A novel algorithm for utilizing molecular testing at our institution was developed with the Korean TI-RADS and with recommendations from the American Thyroid Association and National Comprehensive Cancer Network.

Results: The Korean TI-RADS performed best in our population (area under the curve = 0.83). A positive molecular test result had a positive association with a higher ROM according to all 4 models ( < .05). Use of our algorithm prior to molecular testing would have prevented 38% of benign/low-ROM negative nodules (n = 28) from being tested.

Conclusion: In patients with indeterminate thyroid nodules, an algorithm built on pre- and posttest probability to guide molecular testing might reduce unnecessary testing of benign and low-risk nodules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/01945998211004155DOI Listing
March 2021

Factors predicting positive CT mesenteric angiography results in lower gastrointestinal haemorrhage prior to consideration of intra-arterial angio-embolisation.

J Med Imaging Radiat Oncol 2021 Mar 28. Epub 2021 Mar 28.

Dandenong and Districts Hospital, Monash Health, Dandenong, Victoria, Australia.

Introduction: Lower gastrointestinal haemorrhage (LGIH) is a challenging phenomenon in a comorbid, elderly population. CT mesenteric angiography (CTMA) allows localisation of the site of haemorrhage, and provides a target for interventional techniques, but the intermittent nature of LGIH makes it challenging to reliably demonstrate extravasation. This study aimed to identify objective factors that may predict scan outcomes.

Methods: In this retrospective cohort study, all patients undergoing CTMA for LGIH at Monash Health from January 2011 to December 2019 (n = 854) were included. Baseline patient characteristics included age, bowel resection/endoscopic intervention within the past 14 days, known bowel malignancy, anticoagulant/antiplatelet use, duration of symptoms, vital signs, transfusion requirements in the past 24 h and investigation results (recent haemoglobin levels, platelet count, international normalised ratio and creatinine levels). Univariate analysis was performed, and significant factors were entered into a multivariate model.

Results: The final multivariate model was statistically significant (P < 0.001) and consisted of bowel resection/endoscopic intervention within the past 14 days (OR = 2.15), use of antiplatelet agents (OR = 2.03), blood transfusion requirement greater than 3 units per 24 h (OR = 1.79), systolic blood pressure less than 100 mmHg (OR = 1.56) and heart rate greater than 100 beats per minute (OR = 1.52).

Conclusion: The factors identified above are objective, independently associated with positive scan outcomes, readily available to radiologists and are useful for more judicious patient selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1754-9485.13176DOI Listing
March 2021

Computed Tomography and Magnetic Resonance Imaging are Similarly Reliable in the Assessment of Glenohumeral Arthritis and Glenoid Version.

Arch Bone Jt Surg 2021 Jan;9(1):64-69

University of Tennessee-Campbell Clinic Department of Orthopaedic Surgery and Biomedical Engineering, Memphis, Tennessee, USA.

Background: The purpose of this study was to compare the intraobserver and interobserver reliability of CT and T2-weighted MRI for evaluation of the severity of glenoid wear, glenohumeral subluxation, and glenoid version.

Methods: Sixty-one shoulders with primary osteoarthritis had CT and MRI scans before shoulder arthroplasty. All slices were blinded and randomized before evaluation. Two fellowship-trained shoulder surgeons and three orthopaedic surgery trainees reviewed the images to classify glenoid wear (Walch and Mayo classifications) and glenohumeral subluxation (Mayo classification). Glenoid version was measured using Friedman's technique. After a minimum two-week interval, the process was repeated.

Results: Intraobserver reliability was good for the CT group and fair-to-good for the MRI group for the Walch, Mayo glenoid, and Mayo subluxation classifications; interobserver reliability was poor for the CT and fair-to-poor for the MRI group. For the measurement of glenoid version, intraobserver reliability was good for the CT and substantial for the MRI group; interobserver agreement was good for both groups. There were no significant differences in reliability between staff surgeons and trainees for any of the classifications or measurements.

Conclusion: CT and MRI appear similarly reliable for the classification of glenohumeral wear patterns. For the measurement of glenoid version, MRI was slightly more reliable than CT within observers. Differences in training level did not produce substantial differences in agreement, suggesting these systems can be applied by observers of different experience levels with similar reliability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/abjs.2020.38922.2035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957105PMC
January 2021

Abilities, Motivations, and Opportunities of Furloughed Employees in the Context of Covid-19: Preliminary Evidence From the UK.

Front Psychol 2021 11;12:635144. Epub 2021 Mar 11.

Huddersfield Business School, University of Huddersfield, Huddersfield, United Kingdom.

The Covid-19 global pandemic is a crisis like no other, forcing governments to implement prolonged national lockdowns in an effort to limit the spread of the disease. As organizations aim to adapt and remain operational, employers can suspend or reduce work activity for events related to Covid-19 and claim government support to subsidize employee wages. In this way, some employees are placed on furlough (i.e., temporary unemployment) as opposed to being made redundant. While the impact of such schemes on global economy attracted much attention, their micro-level impact on individual employees is still unknown. Building on the (AMO) framework, this pilot study explores how employees' perceptions of abilities, motivation, and opportunities are affected as a result of furlough. Rapid ethnography including interviews, observations, and document analysis in a British organization provided insights into the perceptions and experiences of employees put on furlough and highlighted that all three elements of AMO are affected by the current situation, either positively or negatively. We identify theoretical contributions and suggest a number of AMO enhancing practices in the context of furlough.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.635144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991597PMC
March 2021

Day at the Races: Comparing BioFire FilmArray Blood Culture ID Panels to Verigene Blood Culture in Gram-negative Bloodstream Infections using DOOR-MAT Analysis.

Clin Infect Dis 2021 Mar 27. Epub 2021 Mar 27.

Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Three RDT platforms (Verigene BC-GN, BioFire® BCID, and BCID 2 (RUO)) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR -MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels different organism and resistance detection. BioFire BCID (RUO) had the best mean DOOR-MAT scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab262DOI Listing
March 2021

Phone call success.

Br Dent J 2021 Mar;230(6):326

By email, St Helens, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41415-021-2860-zDOI Listing
March 2021

IV treatment increase?

Br Dent J 2021 Mar;230(6):324

By email, St Helens, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41415-021-2847-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995384PMC
March 2021

Older lesbian, gay, bisexual, transgender, queer and intersex peoples' experiences and perceptions of receiving home care services in the community: A systematic review.

Int J Nurs Stud 2021 Feb 25;118:103907. Epub 2021 Feb 25.

Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, North Holmes Road, Canterbury, Kent CT1 1QU, United Kingdom.

Background: Numbers of older lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI+) people are increasing worldwide in line with the ageing populations of many countries. Most LGBTQI+ people want to remain in their own homes as they age, making it important to understand their experiences and perceptions of receiving home care. This systematic review aimed to examine older (over 60 years) LGBTQI+ people's perceptions and experiences of using formal home care services in the community.

Methods: The following six electronic databases were searched from the date of their first records until the first week of March 2020: MEDLINE; PsycINFO; Social Policy and Practice; CINAHL; SSCI; and ASSIA. Hand searches of the reference lists of the included studies and relevant reviews were also conducted. Only peer reviewed research published in English was included. There were no restrictions on study design. Findings were analysed using narrative synthesis. The PROSPERO protocol registration identification number is: CRD42020168443.

Results: Seven studies involving 169 participants were included in the synthesis. All were qualitative. Most participants were either lesbian women or gay men, with no studies investigating home care for transgender, queer, intersex or other sexual minorities. Fear of accessing home care services due to the perceived threat of homophobia and past negative experiences of discrimination were common. Some concealed any LGBTQI+ materials in their homes to try and hide their sexuality from home care workers. Despite fear of discrimination, lesbian women and gay men reported wanting and expecting the same level of care, dignity and respect as their heterosexual counterparts. Mandatory LGBTQI+ sensitivity training for home care workers was identified for reducing homophobia and increasing the inclusivity of service providers.

Conclusion: Older lesbian women and gay men fear or experience discrimination from home care workers, with some choosing to hide their sexuality causing stress and anxiety. Sensitivity training in the needs of older LGBTQI+ people should be considered by home care service providers as a way of reducing homophobic attitudes which may exist among some home care workers. Due to the paucity of studies and their focus on older lesbian women and gay men, more research is needed to explore the experiences of other sexual minorities receiving home care services who are represented by the LGBTQI+ umbrella term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijnurstu.2021.103907DOI Listing
February 2021

No pain, all gain? Interim analyses from a longitudinal, observational study examining the impact of medical cannabis treatment on chronic pain and related symptoms.

Exp Clin Psychopharmacol 2021 Mar 25. Epub 2021 Mar 25.

Cognitive and Clinical Neuroimaging Core.

Previous studies have demonstrated improvements in pain following short-term medical cannabis (MC) use, suggesting long-term MC treatment may alleviate symptoms associated with chronic pain. The goal of this observational and longitudinal study was to examine patients using MC to treat chronic pain pre versus post MC treatment. These interim analyses included 37 patients with chronic pain evaluated prior to initiation of MC treatment and following 3 and 6 months of MC use; pain, clinical state, sleep, quality of life, and conventional medication use were assessed. Correlation analyses examined the relationship between changes in pain and other clinical measures, assessed the impact of cannabinoid exposure on pain and clinical ratings, and assessed whether baseline cannabis expectancies influenced outcome variables. Additionally, a pilot group of treatment-as-usual patients (n = 9) who did not use MC were examined at baseline and 3 months later. Relative to baseline, following 3 and 6 months of treatment, MC patients exhibited improvements in pain which were accompanied by improved sleep, mood, anxiety, and quality of life, and stable conventional medication use. Reduced pain was associated with improvements in aspects of mood and anxiety. The results generally suggest increased THC exposure was related to pain-related improvement, while increased CBD exposure was related to improved mood. Cannabis expectancies were not related to observed improvements. Pilot analyses revealed that treatment-as-usual patients do not demonstrate the same pattern of improvement. Findings highlight the potential efficacy of MC treatment for pain and underscore the unique impact of individual cannabinoids on specific aspects of pain and comorbid symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/pha0000435DOI Listing
March 2021