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  1. Article ; Online: Ionic current driven by a viscosity gradient.

    Wiener, Benjamin / Stein, Derek

    Faraday discussions

    2023  Volume 246, Page(s) 47–59

    Abstract: Gradients of voltage, pressure, temperature, and salinity can transport objects in micro- and nanofluidic systems by well-known mechanisms. This paper explores the dynamics of particles in a viscosity gradient with numerical simulations. The different ... ...

    Abstract Gradients of voltage, pressure, temperature, and salinity can transport objects in micro- and nanofluidic systems by well-known mechanisms. This paper explores the dynamics of particles in a viscosity gradient with numerical simulations. The different stochastic rules used to integrate the random motion of Brownian particles affect the steady-state distribution of particles in a diffusivity gradient. Importantly, the simulations illuminate the important role that the boundary conditions play, disallowing a steady-state flux when the boundary conditions mimic those of a closed container, but allowing flux when they mimic electrodes. These results provide an interpretation for measurements of a steady ionic current flowing between electrodes separated by a nanofluidic channel with a liquid viscosity gradient.
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article
    ISSN 1364-5498
    ISSN (online) 1364-5498
    DOI 10.1039/d3fd00053b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Drug-related physician continuing medical education requirements, 2010-2020.

    Davis, Corey S / Carr, Derek H / Stein, Bradley D

    Journal of substance use and addiction treatment

    2024  Volume 161, Page(s) 209356

    Abstract: Introduction: The crisis of drug-related harm in the United States continues to worsen. While prescription-related overdoses have fallen dramatically, they are still far above pre-2010 levels. Physicians can reduce the risk of overdose and other drug- ... ...

    Abstract Introduction: The crisis of drug-related harm in the United States continues to worsen. While prescription-related overdoses have fallen dramatically, they are still far above pre-2010 levels. Physicians can reduce the risk of overdose and other drug-related harms by improving opioid prescribing practices and ensuring that patients are able to easily access medications for substance use disorder treatment. Most physicians received little or no training in those subjects in medical school. It is possible that continuing medical education can improve physician knowledge of appropriate prescribing and substance use disorder treatment and patient outcomes.
    Methods: Descriptive legal review. Laws in all 50 states and the District of Columbia were searched for provisions that require all or most physicians to receive either one-time or continuing medical education regarding controlled substance prescribing, pain management, or substance use disorder treatment.
    Results: There has been a rapid increase in the number of states with relevant requirements, from three states at the end of 2010 to 42 at the end of 2020. The frequency and duration of required education varied substantially across states. In all states, the number of hours required in relevant topics is a small fraction of overall required continuing education, an average of 1 h per year. Despite recent shifts in the substances driving overdose, most requirements remain focused on opioids.
    Conclusion: While most states have now adopted continuing education requirements regarding controlled substance prescribing, pain management, or substance use disorder treatment, these requirements comprise a small component of the required post-training education requirements. Research is needed to determine whether this training translates into reductions in drug-related harm.
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 2949-8759
    ISSN (online) 2949-8759
    DOI 10.1016/j.josat.2024.209356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nanopore Sequencing: Forcing Improved Resolution.

    Stein, Derek

    Biophysical journal

    2015  Volume 109, Issue 10, Page(s) 2001–2002

    MeSH term(s) Avidin/metabolism ; DNA, Single-Stranded/metabolism ; Motion ; Porins/metabolism ; Temperature
    Chemical Substances DNA, Single-Stranded ; Porins ; Avidin (1405-69-2)
    Language English
    Publishing date 2015-04-29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2015.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A descriptive study of syphilis testing in Manitoba, Canada, 2015-2019.

    Shaw, Souradet / Plourde, Pierre / Klassen, Penny / Stein, Derek

    Canada communicable disease report = Releve des maladies transmissibles au Canada

    2022  Volume 48, Issue 2-3, Page(s) 95–101

    Abstract: Background: In 2018, Manitoba had the highest reported rate of infectious syphilis in Canada, at over three times the national average. Infectious syphilis in Manitoba is centred on young, marginalized heterosexual couples in Winnipeg's inner-city. ... ...

    Abstract Background: In 2018, Manitoba had the highest reported rate of infectious syphilis in Canada, at over three times the national average. Infectious syphilis in Manitoba is centred on young, marginalized heterosexual couples in Winnipeg's inner-city. Subsequently, a public health crisis involving congenital syphilis emerged in Manitoba, just prior to the coronavirus disease 2019 pandemic. Testing and screening (in the case of pregnancy) for syphilis is thought to be an effective measure to reduce the incidence of syphilis and its sequelae. The aim of this study is to describe syphilis testing practices in the general population and amongst pregnant women, during a period of shifting syphilis epidemiology.
    Methods: We used population-based syphilis testing data from Cadham Provincial Laboratory (Winnipeg, Manitoba) for 2015 to 2019. Directly age-standardized rates are reported, and Poisson regression used to model the determinants of testing rates. Rates of prenatal screening are also reported.
    Results: From 2015 to 2019, a total of 386,350 individuals were tested for syphilis. The rate increased annually, from 462 per 10,000 population in 2015 to 704 per 100,000 in 2019, while the female-to-male ratio decreased from 1.8 to 1.6. Prior to 2019, the majority of pregnant women (approximately 60%) were screened once, during the first trimester; however, 2019 saw more women having more than two tests during the course of their pregnancy.
    Conclusion: An overall increase in the number of individuals tested was observed, reflecting the increased rate of syphilis in Manitoba. Prenatal screening patterns shifted in 2019, likely in response to rising congenital syphilis numbers.
    Language English
    Publishing date 2022-02-24
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 1146585-2
    ISSN 1188-4169
    ISSN 1188-4169
    DOI 10.14745/ccdr.v48i23a07
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Integrative analysis of pathogenic variants in glucose-6-phosphatase based on an AlphaFold2 model.

    Sinclair, Matt / Stein, Richard A / Sheehan, Jonathan H / Hawes, Emily M / O'Brien, Richard M / Tajkhorshid, Emad / Claxton, Derek P

    PNAS nexus

    2024  Volume 3, Issue 2, Page(s) pgae036

    Abstract: Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the ... ...

    Abstract Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions governing G6P binding as well as explore the perturbations imposed by disease-linked missense variants by subjecting an AlphaFold2 G6PC1 structural model to molecular dynamics simulations and in silico predictions of thermodynamic stability validated with robust in vitro and in situ biochemical assays. We identify a collection of side chains, including conserved residues from the signature phosphatidic acid phosphatase motif, that contribute to a hydrogen bonding and van der Waals network stabilizing G6P in the active site. The introduction of GSD type 1a mutations modified the thermodynamic landscape, altered side chain packing and substrate-binding interactions, and induced trapping of catalytic intermediates. Our results, which corroborate the high quality of the AF2 model as a guide for experimental design and to interpret outcomes, not only confirm the active-site structural organization but also identify previously unobserved mechanistic contributions of catalytic and noncatalytic side chains.
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ISSN 2752-6542
    ISSN (online) 2752-6542
    DOI 10.1093/pnasnexus/pgae036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dorfman pooling enhances SARS-CoV-2 large-scale community testing efficiency.

    Burtniak, Julian / Hedley, Adam / Dust, Kerry / Van Caeseele, Paul / Bullard, Jared / Stein, Derek R

    PLOS global public health

    2023  Volume 3, Issue 4, Page(s) e0001793

    Abstract: PCR-based analysis is the gold standard for detection of SARS-CoV-2 and was used broadly throughout the pandemic. However, heightened demand for testing put strain on diagnostic resources and the adequate amount of PCR-based testing required exceeded ... ...

    Abstract PCR-based analysis is the gold standard for detection of SARS-CoV-2 and was used broadly throughout the pandemic. However, heightened demand for testing put strain on diagnostic resources and the adequate amount of PCR-based testing required exceeded existing testing capacity. Pooled testing strategies presented an effective method to increase testing capacity by decreasing the number of tests and resources required for laboratory PCR analysis of SARS-CoV-2. We sought to conduct an analysis of SARS-CoV-2 pooling schemes to determine the sensitivity of various sized Dorfman pooling strategies and evaluate the utility of using such pooling strategies in diagnostic laboratory settings. Overall, a trend of decreasing sensitivity with larger pool sizes was observed, with modest sensitivity losses in the largest pools tested, and high sensitivity in all other pools. Efficiency data was then calculated to determine the optimal Dorfman pool sizes based on test positivity rate. This was correlated with current presumptive test positivity to maximize the number of tests saved, thereby increasing testing capacity and resource efficiency in the community setting. Dorfman pooling methods were evaluated and found to offer a high-throughput solution to SARS-CoV-2 clinical testing that improve resource efficiency in low-resource environments.
    Language English
    Publishing date 2023-04-18
    Publishing country United States
    Document type Journal Article
    ISSN 2767-3375
    ISSN (online) 2767-3375
    DOI 10.1371/journal.pgph.0001793
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Liposomal Bupivacaine Decreases Intravenous Opioid Use in Patients with Hip Fracture: A Modification to a Novel Pain Protocol.

    Stevenson, Kimberly L / Stein, Matthew K / Fryhofer, George W / Looby, Sean / Donegan, Derek / Mehta, Samir

    The Journal of the American Academy of Orthopaedic Surgeons

    2023  Volume 31, Issue 5, Page(s) e246–e255

    Abstract: Introduction: The aim of this study was to determine whether the administration of liposomal bupivacaine decreased opioid use and delirium in patients sustaining a hip fracture.: Methods: A retrospective review of patients with hip fracture from ... ...

    Abstract Introduction: The aim of this study was to determine whether the administration of liposomal bupivacaine decreased opioid use and delirium in patients sustaining a hip fracture.
    Methods: A retrospective review of patients with hip fracture from September 2018 to October 2019 was performed through our institution's hip fracture registry. A liposomal bupivacaine cocktail was administered intraoperatively. Opioid requirement was determined for postoperative days 1, 2, and 3. Delirium was identified through chart review. Visual analog scale pain scores were averaged for postoperative days 1, 2, and 3. Four groups were analyzed: patients who received liposomal bupivacaine and IV acetaminophen, patients who only received IV acetaminophen, patients who only received liposomal bupivacaine, and control patients whose data were collected before this intervention. Continuous data were compared using a one-way analysis of variance or Student t-test, as applicable. Categorical data were compared using the Fisher exact test. Significance was set at P < 0.05.
    Results: One hundred nine patients met the inclusion criteria for the study with a mean age of 81.2 years. Eighty-two patients (75.2%) received intraoperative liposomal bupivacaine during the study year. Intravenous opioid requirement was markedly different among all four groups in all postoperative days. Oral opioid requirement and pain scores were not different between groups on any postoperative day. A notable decrease in IV opioid requirement in all postoperative days was seen in the Intervention groups (day 1 P < 0.001, day 2 P = 0.002, and day 3 P = 0.030). There existed a trend toward decreased delirium rates in the Intervention groups compared with the No Intervention group (23.9% vs. 32.8%, P = 0.272).
    Conclusion: The inclusion of liposomal bupivacaine in our institution's novel pain protocol led to notable decreases in opioid requirement in all postoperative days studied with a trend toward decreased delirium rates as well.
    MeSH term(s) Humans ; Aged, 80 and over ; Analgesics, Opioid ; Bupivacaine ; Anesthetics, Local ; Pain, Postoperative/drug therapy ; Acetaminophen ; Pain Management/methods ; Opioid-Related Disorders ; Retrospective Studies ; Hip Fractures ; Delirium/chemically induced
    Chemical Substances Analgesics, Opioid ; Bupivacaine (Y8335394RO) ; Anesthetics, Local ; Acetaminophen (362O9ITL9D)
    Language English
    Publishing date 2023-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1200524-1
    ISSN 1940-5480 ; 1067-151X
    ISSN (online) 1940-5480
    ISSN 1067-151X
    DOI 10.5435/JAAOS-D-22-00493
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Dorfman pooling enhances SARS-CoV-2 large-scale community testing efficiency.

    Julian Burtniak / Adam Hedley / Kerry Dust / Paul Van Caeseele / Jared Bullard / Derek R Stein

    PLOS Global Public Health, Vol 3, Iss 4, p e

    2023  Volume 0001793

    Abstract: PCR-based analysis is the gold standard for detection of SARS-CoV-2 and was used broadly throughout the pandemic. However, heightened demand for testing put strain on diagnostic resources and the adequate amount of PCR-based testing required exceeded ... ...

    Abstract PCR-based analysis is the gold standard for detection of SARS-CoV-2 and was used broadly throughout the pandemic. However, heightened demand for testing put strain on diagnostic resources and the adequate amount of PCR-based testing required exceeded existing testing capacity. Pooled testing strategies presented an effective method to increase testing capacity by decreasing the number of tests and resources required for laboratory PCR analysis of SARS-CoV-2. We sought to conduct an analysis of SARS-CoV-2 pooling schemes to determine the sensitivity of various sized Dorfman pooling strategies and evaluate the utility of using such pooling strategies in diagnostic laboratory settings. Overall, a trend of decreasing sensitivity with larger pool sizes was observed, with modest sensitivity losses in the largest pools tested, and high sensitivity in all other pools. Efficiency data was then calculated to determine the optimal Dorfman pool sizes based on test positivity rate. This was correlated with current presumptive test positivity to maximize the number of tests saved, thereby increasing testing capacity and resource efficiency in the community setting. Dorfman pooling methods were evaluated and found to offer a high-throughput solution to SARS-CoV-2 clinical testing that improve resource efficiency in low-resource environments.
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 670
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Molecular mechanisms of catalytic inhibition for active site mutations in glucose-6-phosphatase catalytic subunit 1 linked to glycogen storage disease.

    Sinclair, Matt / Stein, Richard A / Sheehan, Jonathan H / Hawes, Emily M / O'Brien, Richard M / Tajkhorshid, Emad / Claxton, Derek P

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein G6PC1 regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. ... ...

    Abstract Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein G6PC1 regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 cause glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. Exploiting a computational model of G6PC1 derived from the groundbreaking structure prediction algorithm AlphaFold2 (AF2), we combine molecular dynamics (MD) simulations and computational predictions of thermodynamic stability with a robust
    Language English
    Publishing date 2023-08-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.13.532485
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Training Surgery Residents to be Leaders: Construction of a Resident Leadership Curriculum.

    Stein, Matthew K / Kelly, John D / Useem, Michael / Donegan, Derek J / Levin, L Scott

    Plastic and reconstructive surgery

    2022  Volume 149, Issue 3, Page(s) 765–771

    Abstract: Summary: Historically, the traditional pathways into plastic surgery required board eligibility in a surgical specialty such as general surgery, orthopedics, urology, neurosurgery, otolaryngology, or ophthalmology. This requirement resulted in plastic ... ...

    Abstract Summary: Historically, the traditional pathways into plastic surgery required board eligibility in a surgical specialty such as general surgery, orthopedics, urology, neurosurgery, otolaryngology, or ophthalmology. This requirement resulted in plastic surgery residents who had served as chief residents before plastic surgery training. Their maturity emotionally and surgically allowed them to immediately concentrate on the new language and principles of plastic surgery. They had led others and were capable of leading themselves in a new surgical discipline. Today, medical students typically match into surgical specialties directly out of medical school and need to spend their time learning basic surgical skills and patient care because of the contracted time afforded to them. Formal leadership training has historically been limited in surgical training. The authors set out to delineate the creation, implementation, and perceptions of a leadership program within a surgical residency and provide guideposts for the development of engaged, conscious, and dedicated leaders within the residencies they lead.
    MeSH term(s) Curriculum ; Humans ; Internship and Residency/methods ; Internship and Residency/organization & administration ; Leadership ; Pennsylvania ; Surgery, Plastic/education ; Surgery, Plastic/organization & administration
    Language English
    Publishing date 2022-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208012-6
    ISSN 1529-4242 ; 0032-1052 ; 0096-8501
    ISSN (online) 1529-4242
    ISSN 0032-1052 ; 0096-8501
    DOI 10.1097/PRS.0000000000008853
    Database MEDical Literature Analysis and Retrieval System OnLINE

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