Publications by authors named "A Whitney Moses"

711 Publications

Meningeal blood-brain barrier disruption in acute traumatic brain injury.

Brain Commun 2020 9;2(2):fcaa143. Epub 2020 Sep 9.

Acute Cerebrovascular Diagnostics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

The meninges serve as a functional barrier surrounding the brain, critical to the immune response, and can be compromised following head trauma. Meningeal enhancement can be detected on contrast-enhanced MRI in patients presenting with acute traumatic brain injury, even when head CT is negative. Following head trauma, gadolinium-based contrast appears to extravasate from the vasculature, enhancing the dura within minutes, and later permeates the subarachnoid space. The aims of this study were to characterize the initial kinetics of the uptake of contrast agent after injury and the delayed redistribution of contrast enhancement in the subarachnoid space in hyperacute patients. Neuroimaging was obtained prospectively in two large ongoing observational studies of patients aged 18 years or older presenting to the emergency department with suspected acute head injury. Dynamic contrast-enhanced MRI studies in a cohort of consecutively enrolling patients with mild traumatic brain injury ( = 36) determined that the kinetic half-life of dural-related meningeal enhancement was 1.3 ± 0.6 min (95% enhancement within 6 min). The extravasation of contrast into the subarachnoid space was investigated in a cohort of CT negative mild traumatic brain injury patients initially imaged within 6 h of injury (hyperacute) who subsequently underwent a delayed MRI, with no additional contrast administration, several hours after the initial MRI. Of the 32 patients with delayed post-contrast imaging, 18 (56%) had conspicuous expansion of the contrast enhancement into the subarachnoid space, predominantly along the falx and superior sagittal sinus. Patients negative for traumatic meningeal enhancement on initial hyperacute MRI continued to have no evidence of meningeal enhancement on the delayed MRI. These studies demonstrate that (i) the initial enhancement of the traumatically injured meninges occurs within minutes of contrast injection, suggesting highly permeable meningeal vasculature, and that (ii) contrast in the meninges redistributes within the subarachnoid space over the period of hours, suggesting a compromise in the blood-brain and/or blood-cerebrospinal barriers. Data from the parent study indicate that up to one in two patients with mild traumatic brain injury have traumatic brain injury on acute (<48 h) MRI, with a higher prevalence seen in patients with moderate or severe traumatic brain injury. The current study's findings of traumatic meningeal enhancement and the subsequent delayed extravasation of contrast into the subarachnoid spaces indicate that a substantial percentage of patients with even mild traumatic brain injury may have a transient disruption in barriers separating the vasculature from the brain.
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http://dx.doi.org/10.1093/braincomms/fcaa143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869431PMC
September 2020

Application of artificial neural network modeling techniques to signal strength computation.

Heliyon 2021 Mar 18;7(3):e06047. Epub 2021 Mar 18.

Department of Physics, Federal University of Technology, P.M.B. 65, Minna, Niger State, Nigeria.

This paper presents development of artificial neural network (ANN) models to compute received signal strength (RSS) for four VHF (very high frequency) broadcast stations using measured atmospheric parameters. The network was trained using Levenberg-Marquardt back-propagation (LMBP) algorithm. Evaluation of different effects of activation functions at the hidden and output layers, variation of number of neurons in the hidden layer and the use of different types of data normalisation were systematically applied in the training process. The mean and variance of calculated MSE (mean square error) for ten different iterations were compared for each network. From the results, the ANN model performed reasonably well as computed signal strength values had a good fit with the measured values. The computed MSE were very low with values ranging between 0.0027 and 0.0043. The accuracy of the trained model was tested on different datasets and it yielded good results with MSE of 0.0069 for one dataset and 0.0040 for another dataset. The measured field strength was also compared with ANN and ITU-R P. 526 diffraction models and a strong correlation was found to exist between the measured field strength and ANN computed signals, but no correlation existed between the measured field strength and the predicted field strength from diffraction model. ANN has thus proved to be a useful tool in computing signal strength based on atmospheric parameters.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005760PMC
March 2021

Exploring Relationships Between Genito-Pelvic Pain/Penetration Disorder, Sex Guilt, and Religiosity Among College Women in the U.S.

J Sex Med 2021 Mar 20. Epub 2021 Mar 20.

Emory University, Atlanta, GA, USA.

Introduction: Despite a growing body of research on psychosocial factors in Genito-Pelvic Pain/Penetration Disorder (GPPPD) during sexual intercourse, there are few studies examining adolescent and young adult women's experiences with painful sex and the effects of religiosity, sexual education, and sex guilt.

Aim: The purpose of the study was to examine the occurrence of GPPPD among sexually active female college students, including psychosocial factors of religiosity and religious practice, sexual education, sex guilt, and sexual distress.

Methods: Data were collected from 974 college women from a university in the Northeastern U.S. We limited our sample to sexually active women (n = 593, 60.9%; mean age: 18.96) who responded to the questionnaire item, "In general, do you feel pain with sexual intercourse?" Participants completed the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), Revised Mosher Sex Guilt Scale, Abbreviated Santa Clara Strength of Religious Faith Questionnaire, 10-item Gender Role Beliefs Scale, and measures on sexual wellness and practice and sexual education experiences. Data were analyzed using standard bivariate and regression analyses as well as path analysis.

Main Outcome Measures: Women were asked, "In general, do you feel pain with sexual intercourse?" and categorized into one of three pain groups: occasional (10%-25% of the time), frequent (50% or more), and no pain (less than 10%).

Results: GPPPD with sex was prevalent among young college women, with 113 (19.1%) reporting frequent pain and 143 (24.1%) occasional pain (control n = 337, 56.8%). Numerous statistically significant factors were identified, including frequency of sex, ability to orgasm, sensations during intercourse, presence of a steady sexual partner, expectations of painful sex, sex guilt, and sexual distress. Sex guilt acted as full mediator between religiosity and painful sex.

Implications: Healthcare providers should proactively initiate conversations with young female patients about painful intercourse to identify issues and normalize language on pain with sex. Educators are urged to teach evidence-based information on pain-free and guilt-free sexual experiences inside and outside religious contexts.

Conclusion: Painful sex affects adolescent and young adult women at a similar rate as non-college adult women and while religiosity does not directly impact young women's GPPPD, religiosity does lead to painful sex if it causes sex guilt. Further research is needed into the mechanisms of religion-based sexual shaming and among religiously conservative women who practice abstinence until marriage. Azim KA, Happel-Parkins A, Moses A, et al. Exploring Relationships Between Genito-Pelvic Pain/Penetration Disorder, Sex Guilt, and Religiosity Among College Women in the U.S. J Sex Med 2021;xxx:xxx-xxx.
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http://dx.doi.org/10.1016/j.jsxm.2021.02.003DOI Listing
March 2021

A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells.

Genome Res 2021 Apr 12;31(4):564-575. Epub 2021 Mar 12.

Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, M5S 3G5, Canada.

Transcriptional enhancers are critical for development and phenotype evolution and are often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. To examine the enhancer regulatory code for pluripotent stem cells, we identified genomic regions with conserved binding of multiple transcription factors in mouse and human embryonic stem cells (ESCs). Examination of these regions revealed that they contain on average 12.6 conserved transcription factor binding site (TFBS) sequences. Enriched TFBSs are a diverse repertoire of 70 different sequences representing the binding sequences of both known and novel ESC regulators. Using a diverse set of TFBSs from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. Site-directed mutagenesis of conserved TFBSs in endogenous enhancers or TFBS deletion from synthetic sequences revealed a requirement for 10 or more different TFBSs. Furthermore, specific TFBSs, including the POU5F1:SOX2 comotif, are dispensable, despite cobinding the POU5F1 (also known as OCT4), SOX2, and NANOG master regulators of pluripotency. These findings reveal that a TFBS sequence diversity threshold overrides the need for optimized regulatory grammar and individual TFBSs that recruit specific master regulators.
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http://dx.doi.org/10.1101/gr.272468.120DOI Listing
April 2021

Identifying molecular features that are associated with biological function of intrinsically disordered protein regions.

Elife 2021 Feb 22;10. Epub 2021 Feb 22.

Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.

In previous work, we showed that intrinsically disordered regions (IDRs) of proteins contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al., 2019). Here, we aim to use these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions. We find that the predictable functions are diverse. Examining the associated molecular features, we note some that are consistent with previous reports and identify others that were previously unknown. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.
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http://dx.doi.org/10.7554/eLife.60220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932695PMC
February 2021

Stochastic models for single-cell data: Current challenges and the way forward.

FEBS J 2021 Feb 11. Epub 2021 Feb 11.

Department of Cell & Systems Biology, University of Toronto, ON, Canada.

Although the quantity and quality of single-cell data have progressed rapidly, making quantitative predictions with single-cell stochastic models remains challenging. The stochastic nature of cellular processes leads to at least three challenges in building models with single-cell data: (a) because variability in single-cell data can be attributed to multiple different sources, it is difficult to rule out conflicting mechanistic models that explain the same data equally well; (b) the distinction between interesting biological variability and experimental variability is sometimes ambiguous; (c) the nonstandard distributions of single-cell data can lead to violations of the assumption of symmetric errors in least-squares fitting. In this review, we first discuss recent studies that overcome some of the challenges or set up a promising direction and then introduce some powerful statistical approaches utilized in these studies. We conclude that applying and developing statistical approaches could lead to further progress in building stochastic models for single-cell data.
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http://dx.doi.org/10.1111/febs.15760DOI Listing
February 2021

Responses to COVID-19: The role of governance, healthcare infrastructure, and learning from past pandemics.

J Bus Res 2021 Jan 10;122:597-607. Epub 2020 Sep 10.

Indian Institute of Management Ahmedabad, Ahmedabad, India.

The ongoing COVID-19 outbreak has revealed vulnerabilities in global healthcare responses. Research in epidemiology has focused on understanding the effects of countries' responses on COVID-19 spread. While a growing body of research has focused on understanding the role of macro-level factors on responses to COVID-19, we have a limited understanding of what drives countries' responses to COVID-19. We lean on organizational learning theory and the extant literature on rare events to propose that governance structure, investment in healthcare infrastructure, and learning from past pandemics influence a country's response regarding reactive and proactive strategies. With data collected from various sources and using an empirical methodology, we find that centralized governance positively affects reactive strategies, while healthcare infrastructure and learning from past pandemics positively influence proactive and reactive strategies. This research contributes to the literature on learning, pandemics, and rare events.
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http://dx.doi.org/10.1016/j.jbusres.2020.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834581PMC
January 2021

Pain Management Strategies After Anterior Cruciate Ligament Reconstruction: A Systematic Review With Network Meta-analysis.

Arthroscopy 2021 04 28;37(4):1290-1300.e6. Epub 2021 Jan 28.

Sports Medicine Division, Orthopaedic Surgery Department, NYU Langone Health, New York, New York, U.S.A.

Purpose: To systematically review randomized controlled trials (RCTs) evaluating various pain control interventions after anterior cruciate ligament reconstruction (ACLR) to determine the best-available evidence in managing postoperative pain and to optimize patient outcomes.

Methods: A systematic review of the literature was performed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A study was included if it was an RCT evaluating an intervention to reduce postoperative pain acutely after ACLR in one of the following areas: (1) nerve blocks, (2) nerve block adjuncts, (3) intra-articular injections, (4) oral medications, (5) intravenous medications, (6) tranexamic acid, and (7) compressive stockings and cryotherapy. Quantitative and qualitative statistics were carried out, and network meta-analysis was performed where applicable.

Results: Overall, 74 RCTs were included. Across 34 studies, nerve blocks were found to significantly reduce postoperative pain and opioid use, but there was no significant difference among the various nerve blocks in the network meta-analysis. Intra-articular injections consisting of bupivacaine and an adjunct were found to reduce reported postoperative pain scores up to 12 hours after ACLR, with significantly lower postoperative opioid use.

Conclusions: Nerve blocks and regional anesthesia are the mainstay treatment of postoperative pain after ACLR, with the commonly used nerve blocks being equally efficacious. Intra-articular injections consisting of bupivacaine and an adjunct were found to reduce reported postoperative pain scores up to 12 hours after ACLR, with significantly lower postoperative opioid use. There was promising evidence for the use of some oral and intravenous medications, tranexamic acid, and nerve block adjuncts, as well as cryotherapy, to control pain and reduce postoperative opioid use.

Level Of Evidence: Level II, systematic review and meta-analysis of RCTs.
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http://dx.doi.org/10.1016/j.arthro.2021.01.023DOI Listing
April 2021

Nanomedicines for Endometriosis: Lessons Learned from Cancer Research.

Small 2021 Feb 25;17(7):e2004975. Epub 2021 Jan 25.

College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.

Endometriosis is an incurable gynecological disease characterized by the abnormal growth of endometrium-like tissue, characteristic of the uterine lining, outside of the uterine cavity. Millions of people with endometriosis suffer from pelvic pain and infertility. This review aims to discuss whether nanomedicines that are promising therapeutic approaches for various diseases have the potential to create a paradigm shift in endometriosis management. For the first time, the available reports and achievements in the field of endometriosis nanomedicine are critically evaluated, and a summary of how nanoparticle-based systems can improve endometriosis treatment and diagnosis is provided. Parallels between cancer and endometriosis are also drawn to understand whether some fundamental principles of the well-established cancer nanomedicine field can be adopted for the development of novel nanoparticle-based strategies for endometriosis. This review provides the state of the art of endometriosis nanomedicine and perspective for researchers aiming to realize and exploit the full potential of nanoparticles for treatment and imaging of the disorder.
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http://dx.doi.org/10.1002/smll.202004975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928207PMC
February 2021

Automated Frailty Screening At-Scale for Pre-Operative Risk Stratification Using the Electronic Frailty Index.

J Am Geriatr Soc 2021 Jan 19. Epub 2021 Jan 19.

Center for Health Care Innovation, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Background: Frailty is associated with numerous post-operative adverse outcomes in older adults. Current pre-operative frailty screening tools require additional data collection or objective assessments, adding expense and limiting large-scale implementation.

Objective: To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post-operative outcomes for nonemergency surgeries.

Design: Retrospective cohort study.

Setting: Academic Medical Center.

Participants: Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019.

Exposures: Frailty as measured by a 54-item electronic frailty index (eFI).

Outcomes And Measurements: Inpatient length of stay, requirements for post-acute care, 30-day readmission, and 6-month all-cause mortality.

Results: Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre-frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post-acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36-2.08), higher rates of 30-day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72-3.52) and higher all-cause mortality (HR = 2.86; 95%CI = 1.84-4.44) over 6 months' follow-up.

Conclusions: The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre-operative frailty screening at scale.
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http://dx.doi.org/10.1111/jgs.17027DOI Listing
January 2021

Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis.

Isr J Health Policy Res 2021 01 15;10(1). Epub 2021 Jan 15.

Central Administration, Hadassah Hebrew University School of Medicine, Jerusalem, Israel.

Measles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018-2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient's status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient's condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.
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http://dx.doi.org/10.1186/s13584-020-00435-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809232PMC
January 2021

Effectiveness of a Nurse-Led Multidisciplinary Intervention vs Usual Care on Advance Care Planning for Vulnerable Older Adults in an Accountable Care Organization: A Randomized Clinical Trial.

JAMA Intern Med 2021 Mar;181(3):361-369

Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Importance: Advance care planning (ACP), especially among vulnerable older adults, remains underused in primary care. Additionally, many ACP initiatives fail to integrate directly into the electronic health record (EHR), resulting in infrequent and disorganized documentation.

Objective: To determine whether a nurse navigator-led ACP pathway combined with a health care professional-facing EHR interface improves the occurrence of ACP discussions and their documentation within the EHR.

Design, Setting, And Participants: This was a randomized effectiveness trial using the Zelen design, in which patients are randomized prior to informed consent, with only those randomized to the intervention subsequently approached to provide informed consent. Randomization began November 1, 2018, and follow-up concluded November 1, 2019. The study population included patients 65 years or older with multimorbidity combined with either cognitive or physical impairments, and/or frailty, assessed from 8 primary care practices in North Carolina.

Interventions: Participants were randomized to either a nurse navigator-led ACP pathway (n = 379) or usual care (n = 380).

Main Outcomes And Measures: The primary outcome was documentation of a new ACP discussion within the EHR. Secondary outcomes included the usage of ACP billing codes, designation of a surrogate decision maker, and ACP legal form documentation. Exploratory outcomes included incident health care use.

Results: Among 759 randomized patients (mean age 77.7 years, 455 women [59.9%]), the nurse navigator-led ACP pathway resulted in a higher rate of ACP documentation (42.2% vs 3.7%, P < .001) as compared with usual care. The ACP billing codes were used more frequently for patients randomized to the nurse navigator-led ACP pathway (25.3% vs 1.3%, P < .001). Patients randomized to the nurse navigator-led ACP pathway more frequently designated a surrogate decision maker (64% vs 35%, P < .001) and completed ACP legal forms (24.3% vs 10.0%, P < .001). During follow-up, the incidence of emergency department visits and inpatient hospitalizations was similar between the randomized groups (hazard ratio, 1.17; 95% CI, 0.92-1.50).

Conclusions And Relevance: A nurse navigator-led ACP pathway integrated with a health care professional-facing EHR interface increased the frequency of ACP discussions and their documentation. Additional research will be required to evaluate whether increased EHR documentation leads to improvements in goal-concordant care.

Trial Registration: ClinicalTrials.gov Identifier: NCT03609658.
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http://dx.doi.org/10.1001/jamainternmed.2020.5950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802005PMC
March 2021

High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy.

PLoS One 2020 28;15(12):e0244131. Epub 2020 Dec 28.

Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States of America.

Introduction: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course.

Methods: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses.

Results: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25).

Conclusions And Relevance: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769434PMC
January 2021

Phase Separation as a Missing Mechanism for Interpretation of Disease Mutations.

Cell 2020 Dec;183(7):1742-1756

Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:

It is unclear how disease mutations impact intrinsically disordered protein regions (IDRs), which lack a stable folded structure. These mutations, while prevalent in disease, are frequently neglected or annotated as variants of unknown significance. Biomolecular phase separation, a physical process often mediated by IDRs, has increasingly appreciated roles in cellular organization and regulation. We find that autism spectrum disorder (ASD)- and cancer-associated proteins are enriched for predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular processes. More generally, we hypothesize that combinations of small-effect IDR mutations perturb phase separation, potentially contributing to "missing heritability" in complex disease susceptibility.
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http://dx.doi.org/10.1016/j.cell.2020.11.050DOI Listing
December 2020

The use of bacterial DNA from saliva for the detection of GAS pharyngitis.

J Oral Microbiol 2020 May 27;12(1):1771065. Epub 2020 May 27.

Department of Microbiology and Infectious Diseases, Hadassah and Hebrew University Hospital, Jerusalem, Israel.

Background: Acute tonsillitis is a very common medical condition. Despite different methods of detection, all tests are based on GAS sampling using a throat swab. However, obtaining the swab can elicit vomiting and is often accompanied by fear and apprehension in children. The aim of this study was to find a non-invasive method for the detection of GAS pharyngitis.

Methods: A classic throat swab was obtained for culture, and a saliva sample was taken from 100 subjects recruited from Meuhedet Health Care Organization clinic. Real time PCR was performed to detect GAS dnaseB specific gene in the saliva samples.

Results: 56% of the throat cultures and 48% of the PCR samples were positive for GAS. The overall sensitivity and specificity of the saliva PCR method was 79% and 91% respectively; NPV and PPV were 77% and 92% respectively. When excluding patients who presented on the first day of fever, sensitivity and specificity increased to 90% and 100% respectively. No other anamnestic or clinical findings increased the yield of the test.

Conclusion: Saliva-based PCR amplification of GAS DNA method is effective in detection of GAS pharyngitis. Further studies are needed to achieve detection rates to replace the traditional throat swab-based approach.
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http://dx.doi.org/10.1080/20002297.2020.1771065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717604PMC
May 2020

The Generalizability of a Medication Administration Discrepancy Detection System: Quantitative Comparative Analysis.

JMIR Med Inform 2020 Dec 2;8(12):e22031. Epub 2020 Dec 2.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

Background: As a result of the overwhelming proportion of medication errors occurring each year, there has been an increased focus on developing medication error prevention strategies. Recent advances in electronic health record (EHR) technologies allow institutions the opportunity to identify medication administration error events in real time through computerized algorithms. MED.Safe, a software package comprising medication discrepancy detection algorithms, was developed to meet this need by performing an automated comparison of medication orders to medication administration records (MARs). In order to demonstrate generalizability in other care settings, software such as this must be tested and validated in settings distinct from the development site.

Objective: The purpose of this study is to determine the portability and generalizability of the MED.Safe software at a second site by assessing the performance and fit of the algorithms through comparison of discrepancy rates and other metrics across institutions.

Methods: The MED.Safe software package was executed on medication use data from the implementation site to generate prescribing ratios and discrepancy rates. A retrospective analysis of medication prescribing and documentation patterns was then performed on the results and compared to those from the development site to determine the algorithmic performance and fit. Variance in performance from the development site was further explored and characterized.

Results: Compared to the development site, the implementation site had lower audit/order ratios and higher MAR/(order + audit) ratios. The discrepancy rates on the implementation site were consistently higher than those from the development site. Three drivers for the higher discrepancy rates were alternative clinical workflow using orders with dosing ranges; a data extract, transfer, and load issue causing modified order data to overwrite original order values in the EHRs; and delayed EHR documentation of verbal orders. Opportunities for improvement were identified and applied using a software update, which decreased false-positive discrepancies and improved overall fit.

Conclusions: The execution of MED.Safe at a second site was feasible and effective in the detection of medication administration discrepancies. A comparison of medication ordering, administration, and discrepancy rates identified areas where MED.Safe could be improved through customization. One modification of MED.Safe through deployment of a software update improved the overall algorithmic fit at the implementation site. More flexible customizations to accommodate different clinical practice patterns could improve MED.Safe's fit at new sites.
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http://dx.doi.org/10.2196/22031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744260PMC
December 2020

A comparative evaluation of shear bond strength between feldspathic porcelain and lithium di silicate ceramic layered to a zirconia core- An study.

J Clin Exp Dent 2020 Nov 1;12(11):e1039-e1044. Epub 2020 Nov 1.

MDS, Prof & Head. Department of prosthodontics, Faculty of dentistry, Meenakshi Academy of Higher Education and Research, Chennai.

Background: The bond strength between the zirconia core and ceramic veneer is the weakest component in the layered structure. Delamination of veneering ceramic is reported as one of the most frequent problems associated with Veneered Zirconia restorations. The aim of this study is to compare the shear bond strength of lithium di silicate porcelain to that of feldspathic porcelain on a zirconia Substrate.

Material And Methods: Two groups (group A and B) of zirconia blocks with each group having 20 samples were fabricated according to Schmitz Schulmeyer method. Group A (n =20 ) samples were veneered with feldspathic veneering porcelain and Group B (n=20) samples were veneered with heat pressed lithium disilicate ceramic. The fabricated samples were then evaluated for shear bond strength in Universal Testing Machine. The values were then statistically analyzed using independent sample t-test.

Results: Results of the current study showed that mean shear bond strength of feldspathic porcelain 11.40±1.29 MPa is comparatively lower than the mean shear bond strength of the lithium disilicate group 18.81±1.76 MPa. The statistical analysis indicated that ( value<0.01) there is a statistically significant difference in the shear bond strength between the two groups.

Conclusions: The heat pressed lithium disilicate veneering materials has a better shear bond strength compared to feldspathic veneering ceramic material when layered to a zirconia core and it can be used as a viable alternative material to feldspathic porcelain layering material in bilayered zirconia restorations. Zirconia, bilayered ceramics, lithium disilicate , shear bond strength, ceramic chipping.
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http://dx.doi.org/10.4317/jced.57569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680571PMC
November 2020

Systemically Delivered Magnetic Hyperthermia for Prostate Cancer Treatment.

Pharmaceutics 2020 Oct 25;12(11). Epub 2020 Oct 25.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR 97201, USA.

Herein, we report a novel therapy for prostate cancer based on systemically delivered magnetic hyperthermia. Conventional magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites via intratumoral administration produce heat in the presence of an alternating magnetic field (AMF). To employ this therapy for prostate cancer tumors that are challenging to inject intratumorally, we designed novel nanoclusters with enhanced heating efficiency that reach prostate cancer tumors after systemic administration and generate desirable intratumoral temperatures upon exposure to an AMF. Our nanoclusters are based on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome the challenges associated with the poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL (methoxy poly(ethylene glycol)--poly(-caprolactone))-based polymeric nanoparticles. Animal studies demonstrated that, following intravenous injection into mice bearing prostate cancer grafts, the nanoclusters efficiently accumulated in cancer tumors within several hours and increased the intratumoral temperature above 42 °C upon exposure to an AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibited prostate cancer growth and did not exhibit any signs of toxicity.
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http://dx.doi.org/10.3390/pharmaceutics12111020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692290PMC
October 2020

What distinguishes positive deviance (PD) health professionals from their peers and what impact does a PD intervention have on behaviour change: a cross-sectional study of infection control and prevention in three Israeli hospitals.

Epidemiol Infect 2020 10 14;148:e259. Epub 2020 Oct 14.

Department of Clinical Microbiology and Infectious Diseases, Hadassah University Medical Center, Ein Kerem, Jerusalem, Israel.

Past studies using the positive deviance (PD) approach in the field of infection prevention and control (IPC) have primarily focused on impacts on healthcare-associated infection rates. This research aimed to determine if health professionals who exhibit PD behaviours have distinctive socio-cognitive profiles compared to non-PD professionals, and to examine the impact of a PD intervention on healthcare professionals' (HPs) behavioural changes in maintaining IPC guidelines. In a cross-sectional study among 135 HPs, respondents first filled out a socio-cognitive characteristics questionnaire, and after 5 months were requested to complete a self-reported behavioural change questionnaire. The main findings indicate that socio-cognitive variables such as external locus of control, perceived threat and social learning were significant predictors of a person exhibiting PD behaviours. Almost 70% of HPs reported behavioural change and creating social networks as a result of the PD intervention in maintaining IPC guidelines, 16.9% of them are a 'PD boosters' (a new group of HPs who have adopted the positive practices of PDs that were originally identified, and also added additional practices of their own). Social networks can contribute to internalizing and raising personal accountability even among non-PD professionals, by creating a mind map that makes each person believe they are an important node in the network, regardless of their status and role. Health intervention programmes should purposely make visible and prominent social network connections in the hospital system.
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http://dx.doi.org/10.1017/S0950268820002484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689599PMC
October 2020

Development of a hypoglycaemia risk score to identify high-risk individuals with advanced type 2 diabetes in DEVOTE.

Diabetes Obes Metab 2020 12;22(12):2248-2256

University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Aims: The ability to differentiate patient populations with type 2 diabetes at high risk of severe hypoglycaemia could impact clinical decision making. The aim of this study was to develop a risk score, using patient characteristics, that could differentiate between populations with higher and lower 2-year risk of severe hypoglycaemia among individuals at increased risk of cardiovascular disease.

Materials And Methods: Two models were developed for the risk score based on data from the DEVOTE cardiovascular outcomes trials. The first, a data-driven machine-learning model, used stepwise regression with bidirectional elimination to identify risk factors for severe hypoglycaemia. The second, a risk score based on known clinical risk factors accessible in clinical practice identified from the data-driven model, included: insulin treatment regimen; diabetes duration; sex; age; and glycated haemoglobin, all at baseline. Both the data-driven model and simple risk score were evaluated for discrimination, calibration and generalizability using data from DEVOTE, and were validated against the external LEADER cardiovascular outcomes trial dataset.

Results: Both the data-driven model and the simple risk score discriminated between patients at higher and lower hypoglycaemia risk, and performed similarly well based on the time-dependent area under the curve index (0.63 and 0.66, respectively) over a 2-year time horizon.

Conclusions: Both the data-driven model and the simple hypoglycaemia risk score were able to discriminate between patients at higher and lower risk of severe hypoglycaemia, the latter doing so using easily accessible clinical data. The implementation of such a tool (http://www.hyporiskscore.com/) may facilitate improved recognition of, and education about, severe hypoglycaemia risk, potentially improving patient care.
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http://dx.doi.org/10.1111/dom.14208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756403PMC
December 2020

Whence Blobs? Phylogenetics of functional protein condensates.

Biochem Soc Trans 2020 10;48(5):2151-2158

Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.

What do we know about the molecular evolution of functional protein condensation? The capacity of proteins to form biomolecular condensates (compact, protein-rich states, not bound by membranes, but still separated from the rest of the contents of the cell) appears in many cases to be bestowed by weak, transient interactions within one or between proteins. Natural selection is expected to remove or fix amino acid changes, insertions or deletions that preserve and change this condensation capacity when doing so is beneficial to the cell. A few recent studies have begun to explore this frontier of phylogenetics at the intersection of biophysics and cell biology.
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http://dx.doi.org/10.1042/BST20200355DOI Listing
October 2020

Harnessing technology and portability to conduct molecular epidemiology of endemic pathogens in resource-limited settings.

Trans R Soc Trop Med Hyg 2021 01;115(1):3-5

Coordinating Office for the Control of Trypanosomiasis in Uganda, Kampala, Uganda.

Improvements in genetic and genomic technology have enabled field-deployable molecular laboratories and these have been deployed in a variety of epidemics that capture headlines. In this editorial, we highlight the importance of building physical and personnel capacity in low and middle income countries to deploy these technologies to improve diagnostics, understand transmission dynamics and provide feedback to endemic communities on actionable timelines. We describe our experiences with molecular field research on schistosomiasis, trypanosomiasis and rabies and urge the wider tropical medicine community to embrace these methods and help build capacity to benefit communities affected by endemic infectious diseases.
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http://dx.doi.org/10.1093/trstmh/traa086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788292PMC
January 2021

Feasibility of Mobile Technology to Identify and Address Patients' Unmet Social Needs in a Primary Care Clinic.

Popul Health Manag 2020 Sep 14. Epub 2020 Sep 14.

Department of Internal Medicine and Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Mobile health tools may overcome barriers to social needs screening; however, there are limited data on the feasibility of using these tools in clinical settings. The objective was to determine the feasibility of using a mobile health system to screen for patients' social needs. In one large primary care clinic, the authors tested a tablet-based system that screens patients for social needs, transmits results to the electronic health record, and alerts providers. All adult patients presenting for a nonurgent visit were eligible. The authors evaluated the feasibility of the system and conducted follow-up surveys to determine acceptability and if patients accessed resources through the process. All providers were surveyed. Of the 252 patients approached, 219 (86.9%) completed the screen. Forty-three (19.6%) required assistance with the tablet, and 150 (68.5%) screened positive for at least 1 unmet need (food, housing, or transportation). Of the 150, 103 (68.7%) completed a follow-up survey. The majority agreed that people would learn to use the tablet quickly. Forty-eight patients (46.6%) reported contacting at least 1 community organization through the process. Of the 27 providers, 23 (85.2%) completed a survey and >70% agreed the system would result in patients having better access to resources. It was feasible to use a tablet-based system to screen for social needs. Clinics considering using mobile tools will need to determine how to screen patients who may need assistance with the tool and how to connect patients to resources through the system based on the burden of unmet needs.
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http://dx.doi.org/10.1089/pop.2020.0059DOI Listing
September 2020

Rituximab identified as an independent risk factor for severe PJP: A case-control study.

PLoS One 2020 11;15(9):e0239042. Epub 2020 Sep 11.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: Pneumocystis jirovecii pneumonia (PJP) was reported among immunosuppressed patients with deficits in cell-mediated immunity and in patients treated with immunomodulatory drugs. The aim of this study was to identify risk-factors for PJP in noninfected HIV patients.

Methods: This retrospective, test negative, case-control study was conducted in six hospitals in Israel, 2006-2016. Cases were hospitalized HIV-negative patients with pneumonia diagnosed as PJP by bronchoalveolar lavage. Controls were similar patients negative for PJP.

Results: Seventy-six cases and 159 controls were identified. Median age was 63.7 years, 65% males, 34% had hematological malignancies, 11% inflammatory diseases, 47% used steroids and 9% received antilymphocyte monoclonal antibodies. PJP was independently associated with antilymphocyte monoclonal antibodies (OR 11.47, CI 1.50-87.74), high-dose steroid treatment (OR 4.39, CI 1.52-12.63), lymphopenia (OR 8.13, CI 2.48-26.60), low albumin (OR 0.15, CI 0.40-0.54) and low BMI (OR 0.80, CI 0.68-0.93).

Conclusion: In conclusion, rituximab, which is prescribed for a wide variety of malignant and inflammatory disorders, was found to be significant risk-factor for PJP. Increased awareness of possible PJP infection in this patient population is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239042PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485893PMC
November 2020

Feasibility of Use of a Smart Speaker to Administer Snellen Visual Acuity Examinations in a Clinical Setting.

JAMA Netw Open 2020 08 3;3(8):e2013908. Epub 2020 Aug 3.

Department of Ophthalmology, Howard University College of Medicine, Washington, DC.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.13908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439105PMC
August 2020

Is it financially beneficial for hospitals to prevent nosocomial infections?

BMC Health Serv Res 2020 Jul 14;20(1):653. Epub 2020 Jul 14.

Critical Care Unit, Shaare Zedek Medical Center, Jerusalem, Israel.

Background: Financial incentives represent a potential mechanism to encourage infection prevention by hospitals. In order to characterize the place of financial incentives, we investigated resource utilization and cost associated with hospital-acquired infections (HAI) and assessed the relative financial burden for hospital and insurer according to reimbursement policies.

Methods: We conducted a prospective matched case-control study over 18 months in a tertiary university medical center. Patients with central-line associated blood-stream infections (CLABSI), Clostridium difficile infection (CDI) or surgical site infections (SSI) were each matched to three control patients. Resource utilization, costs and reimbursement (per diem for CLABSI and CDI, diagnosis related group (DRG) reimbursement for SSI) were compared between patients and controls, from both the hospital and insurer perspective.

Results: HAIs were associated with increased resource consumption (more blood tests, imaging, antibiotic days, hospital days etc.). Direct costs were higher for cases vs. controls (CLABSI: $6400 vs. $2376 (p < 0.001), CDI: $1357 vs $733 (p = 0.047) and SSI: $6761 vs. $5860 (p < 0.001)). However as admissions were longer following CLABSI and CDI, costs per-day were non-significantly different (USD/day, cases vs. controls: CLABSI, 601 vs. 719, (p = 0.63); CDI, 101 vs. 93 (p = 0.5)). For CLABSI and CDI, reimbursement was per-diem and thus the financial burden ($14,608 and $5430 respectively) rested on the insurer, not the hospital. For SSI, as reimbursement was per procedure, costs rested primarily on the hospital rather than the insurer.

Conclusion: Nosocomial infections are associated with both increased resource utilization and increased length of stay. Reimbursement strategy (per diem vs DRG) is the principal parameter affecting financial incentives to prevent hospital acquired infections and depends on the payer perspective. In the Israeli health care system, financial incentives are unlikely to represent a significant consideration in the prevention of CLABSI and CDI.
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http://dx.doi.org/10.1186/s12913-020-05428-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358996PMC
July 2020

Nonspecific wrist pain in pediatric patients: A systematic review.

J Orthop 2020 Nov-Dec;22:308-315. Epub 2020 Jun 13.

Howard University College of Medicine, Howard University Hospital, 520 W St NW, Washington, DC, 20059, USA.

Determining the cause of wrist pain is a challenge for clinicians due to the complex biomechanical characteristics of the multiple articulations which comprise the wrist, and the intricacies of the soft tissue supporting them. Patients presenting with wrist pain can be diagnosed by obtaining a detailed history, physical examination and radiographic images. For some patients, a diagnosis remains elusive even after a complete appropriate work up, and the pain may persist following conservative management. The aim of this systematic review was to analyze the effect that psychosocial factors have on the development chronic idiopathic wrist pain in children and adolescents.
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http://dx.doi.org/10.1016/j.jor.2020.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334546PMC
June 2020

Exploring whole-genome duplicate gene retention with complex genetic interaction analysis.

Science 2020 06;368(6498)

Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.

Whole-genome duplication has played a central role in the genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated, and factors that influence the retention of persisting duplicates remain poorly understood. We describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping of digenic interactions for a deletion mutant of each paralog, and of trigenic interactions for the double mutant, provides insight into their roles and a quantitative measure of their functional redundancy. Trigenic interaction analysis distinguishes two classes of paralogs: a more functionally divergent subset and another that retained more functional overlap. Gene feature analysis and modeling suggest that evolutionary trajectories of duplicated genes are dictated by combined functional and structural entanglement factors.
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http://dx.doi.org/10.1126/science.aaz5667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539174PMC
June 2020

Impact of bleeding after transcatheter aortic valve replacement in patients with chronic kidney disease.

Catheter Cardiovasc Interv 2021 Jan 22;97(1):E172-E178. Epub 2020 May 22.

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objective: In patients with chronic kidney disease (CKD) undergoing transcatheter aortic valve replacement (TAVR), this study aims to elucidate (a) the bleeding risks associated with CKD, (b) the association between bleeding and subsequent mortality, and (c) the pattern of antithrombotic therapy prescribed.

Background: Patients with CKD have a higher risk of bleeding following TAVR. It is unclear whether this risk persists beyond the periprocedural period and whether it negatively impacts mortality.

Methods: A retrospective review was performed on patients who underwent TAVR at Massachusetts General Hospital from 2008 to 2017. CKD was defined as estimated glomerular filtration rate less than 60 ml/min/1.73 m . Primary endpoints up to 1-year following TAVR included bleeding, all-cause mortality, and ischemic stroke. Outcomes for patients with and without CKD were compared using log-rank test, and Cox regression with age, sex, and diabetes as covariates. Bleeding was treated as a time-varying covariate, and Cox proportional hazard regression was utilized to model mortality.

Results: Of the 773 patients analyzed, 466 (60.3%) had CKD. At 1 year, CKD patients had higher rates of bleeding (9.2 vs. 4.9%, adjusted hazard ratios [aHR] = 1.91, p = .032) and all-cause mortality (13.7 vs. 9.1%, aHR = 1.57, p = .049), but not stroke (3.9 vs. 1.6% aHR = 0.073, p = .094). Bleeding was associated with an increased risk of subsequent mortality (aHR = 2.65, 95% CI: 1.25-5.63, p = .01). There were no differences in the antithrombotic strategy following TAVR between CKD and non-CKD patients.

Conclusion: CKD is associated with a higher risk of bleeding up to 1 year following TAVR. Long-term bleeding after TAVR is associated with increased subsequent mortality.
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http://dx.doi.org/10.1002/ccd.28989DOI Listing
January 2021

Impacts of host gender on Schistosoma mansoni risk in rural Uganda-A mixed-methods approach.

PLoS Negl Trop Dis 2020 05 13;14(5):e0008266. Epub 2020 May 13.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Background: The World Health Organization identified Uganda as one of the 10 highly endemic countries for schistosomiasis. Annual mass drug administration (MDA) with praziquantel has led to a decline in intensity of Schistosoma mansoni infections in several areas. However, as hotspots with high (re)infection rates remain, additional research on risk factors and implementing interventions to complement MDA are required to further reduce disease burden in these settings. Through a mixed-methods study we aimed to gain deeper understanding of how gender may impact risk and reinfection in order to inform disease control programmes and ascertain if gender-specific interventions may be beneficial.

Methodology/principal Findings: In Bugoto, Mayuge District, Eastern Uganda we conducted ethnographic observations (n = 16) and examined epidemiology (n = 55) and parasite population genetics (n = 16) in school-aged children (SAC), alongside a community-wide household survey (n = 130). Water contact was frequent at home, school and in the community and was of domestic, personal care, recreational, religious or commercial nature. Qualitative analysis of type of activity, duration, frequency, level of submersion and water contact sites in children showed only few behavioural differences in water contact between genders. However, survey data revealed that adult women carried out the vast majority of household tasks involving water contact. Reinfection rates (96% overall) and genetic diversity were high in boys (pre-He = 0.66; post-He = 0.67) and girls (pre-He = 0.65; post-He = 0.67), but no differences in reinfection rates (p = 0.62) or genetic diversity by gender before (p = 0.54) or after (p = 0.97) treatment were found.

Conclusions/significance: This mixed methods approach showed complementary findings. Frequent water exposure with few differences between boys and girls was mirrored by high reinfection rates and genetic diversity in both genders. Disease control programmes should consider the high reinfection rates among SAC in remaining hotspots of schistosomiasis and the various purposes and settings in which children and adults are exposed to water.
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http://dx.doi.org/10.1371/journal.pntd.0008266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219705PMC
May 2020