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1.
Br Dent J ; 236(9): 688-692, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38730157

RESUMO

Referrals are defined as 'a process in which a health worker at one level of the health system, having insufficient resources (drugs, equipment, skills) to manage a clinical condition, seeks the help of a better or differently resourced facility at the same or higher level to assist in patient management'. Within the UK, the NHS dental service is divided into nationally defined levels of care, which provide treatment based upon complexity and patient modifying factors. Having a sound knowledge of these levels will help general dental practitioners (GDPs) make appropriate and efficient onward referrals to the correct service.This article aims to outline the key information required for all strong GDP referrals, as well as highlighting information that may be specific to each speciality. This is with the hope of creating a key list for GDPs to use on clinic when writing referrals to reduce the incidence of missed information and subsequent rejection. The article also aims to outline the levels of NHS dental care and what factors and treatments are suitable for each to aid GDPs during their referral decision-making process.


Assuntos
Correspondência como Assunto , Encaminhamento e Consulta , Humanos , Reino Unido , Assistência Odontológica/normas , Odontólogos , Odontologia Geral
2.
Res Sq ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38766032

RESUMO

Prostate cancer (PCa) is the most common cancer diagnosed in men worldwide and the second leading cause of cancer-related deaths in US males in 2022. Prostate cancer also represents the second highest cancer mortality disparity between non-Hispanic blacks and whites. However, there is a relatively small number of prostate normal and cancer cell lines compared to other cancers. To identify the molecular basis of PCa progression, it is important to have prostate epithelial cell (PrEC) lines as karyotypically normal as possible. Our lab recently developed a novel methodology for the rapid and efficient immortalization of normal human PrEC that combines simultaneous CRISPR-directed inactivation of CDKN2A exon 2 (which directs expression of p16INK4A and p14ARF) and ectopic expression of an hTERT transgene. To optimize this methodology to generate immortalized lines with minimal genetic alterations, we sought to target exon 1α of the CDKN2A locus so that p16INK4A expression is ablated while p14ARF expression remains unaltered. Here we describe the establishment of two cell lines: one with the above-mentioned p16INK4A only loss, and a second line targeting both products in the CDKN2A locus. We characterize the potential lineage origin of these new cell lines along with our previously obtained clones, revealing distinct gene expression signatures. Based on the analyses of protein markers and RNA expression signatures, these cell lines are most closely related to a subpopulation of basal prostatic cells. Given the simplicity of this one-step methodology and the fact that it uses only the minimal genetic alterations necessary for immortalization, it should also be suitable for the establishment of cell lines from primary prostate tumor samples, an urgent need given the limited number of available prostate cancer cell lines.

3.
Leuk Lymphoma ; : 1-9, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648559

RESUMO

The FLT3 inhibitor quizartinib has been shown to improve overall survival when added to intensive induction chemotherapy ("7 + 3") in patients 18-75 years old with newly diagnosed AML harboring a FLT3-ITD mutation. However, the health economic implications of this approval are unknown. We evaluated the cost-effectiveness of quizartinib using a partitioned survival analysis model. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, the addition of quizartinib to 7 + 3 resulted in incremental costs of $289,932 compared with 7 + 3 alone. With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.

4.
medRxiv ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38633805

RESUMO

Importance: Large language models (LLMs) possess a range of capabilities which may be applied to the clinical domain, including text summarization. As ambient artificial intelligence scribes and other LLM-based tools begin to be deployed within healthcare settings, rigorous evaluations of the accuracy of these technologies are urgently needed. Objective: To investigate the performance of GPT-4 and GPT-3.5-turbo in generating Emergency Department (ED) discharge summaries and evaluate the prevalence and type of errors across each section of the discharge summary. Design: Cross-sectional study. Setting: University of California, San Francisco ED. Participants: We identified all adult ED visits from 2012 to 2023 with an ED clinician note. We randomly selected a sample of 100 ED visits for GPT-summarization. Exposure: We investigate the potential of two state-of-the-art LLMs, GPT-4 and GPT-3.5-turbo, to summarize the full ED clinician note into a discharge summary. Main Outcomes and Measures: GPT-3.5-turbo and GPT-4-generated discharge summaries were evaluated by two independent Emergency Medicine physician reviewers across three evaluation criteria: 1) Inaccuracy of GPT-summarized information; 2) Hallucination of information; 3) Omission of relevant clinical information. On identifying each error, reviewers were additionally asked to provide a brief explanation for their reasoning, which was manually classified into subgroups of errors. Results: From 202,059 eligible ED visits, we randomly sampled 100 for GPT-generated summarization and then expert-driven evaluation. In total, 33% of summaries generated by GPT-4 and 10% of those generated by GPT-3.5-turbo were entirely error-free across all evaluated domains. Summaries generated by GPT-4 were mostly accurate, with inaccuracies found in only 10% of cases, however, 42% of the summaries exhibited hallucinations and 47% omitted clinically relevant information. Inaccuracies and hallucinations were most commonly found in the Plan sections of GPT-generated summaries, while clinical omissions were concentrated in text describing patients' Physical Examination findings or History of Presenting Complaint. Conclusions and Relevance: In this cross-sectional study of 100 ED encounters, we found that LLMs could generate accurate discharge summaries, but were liable to hallucination and omission of clinically relevant information. A comprehensive understanding of the location and type of errors found in GPT-generated clinical text is important to facilitate clinician review of such content and prevent patient harm.

5.
Clin Res Hepatol Gastroenterol ; 48(5): 102337, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609048

RESUMO

BACKGROUND: Cryptococcal disease (CD) confers a higher mortality in cirrhotic patients compared to non-cirrhotic patients. Factor association for CD in cirrhotic patients is poorly understood. Our aim was to determine the incidence, demographic, and comorbidities associated with CD among cirrhotic patients in the United States (US). METHOD: Retrospective analysis of admissions of cirrhotic patients, with or without CD, using the National Inpatient Sample (NIS) database from 2005 to 2014. The number of admissions were reported in raw and weighted frequencies. The trends of CD among cirrhotic patients and overall CD were evaluated. Rao-Scott chi-square, t-tests, and multivariate logistic regressions were performed to evaluate variables and CD among cirrhotic patients. RESULTS: There were 886,962 admissions for cirrhosis, and 164 of these with CD. By adjusted odds ratio (AOR), CD was more often associated with cirrhosis in Southern (2.95; 95 % CI 1.24, 7.02) and Western regions (4.45; 95 % CI 1.91, 10.37), Hispanic patients (1.80; 95 % CI 1.01, 3.20), and patients with chronic kidney disease (CKD) (3.13; 95 % CI 2.09, 4.69). Of note, CD in cirrhotic patients was associated with higher inpatient mortality (AOR of 3.89, 95 % CI 2.53, 5.99), longer length of stay (9.87 vs. 4.88 days), and a higher total charge ($76,880 vs. $ 37,227) when compared to cirrhotic patients without CD. DISCUSSION: Patients with cirrhosis admitted with CD have a high inpatient mortality. The geographical location and CKD were important factors associated with CD among cirrhotic patients. Autoimmune liver diseases and immunosuppression did not appear to increase the risk of CD.


Assuntos
Criptococose , Cirrose Hepática , Humanos , Cirrose Hepática/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Criptococose/complicações , Criptococose/epidemiologia , Estados Unidos/epidemiologia , Idoso , Adulto , Incidência , Fatores de Risco , Pacientes Internados/estatística & dados numéricos
7.
Am J Ophthalmol ; 262: 206-212, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38373583

RESUMO

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.


Assuntos
Migração do Implante de Lente Intraocular , Implante de Lente Intraocular , Lentes Intraoculares , Esclera , Humanos , Esclera/cirurgia , Estudos Transversais , Implante de Lente Intraocular/métodos , Feminino , Masculino , Idoso , Migração do Implante de Lente Intraocular/cirurgia , Migração do Implante de Lente Intraocular/fisiopatologia , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Idoso de 80 Anos ou mais , Facoemulsificação
8.
Innov Aging ; 8(1): igad126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250746

RESUMO

Background and Objectives: Unprecedented social restrictions during the coronavirus disease 2019 (COVID-19) pandemic have provided a new lens for considering the interrelationship between social isolation and loneliness in later life. We present these interrelationships before and during the COVID-19 restrictions and investigate to what extent demographic, socioeconomic, and health factors associated with such experiences differed during the pandemic. Research Design and Methods: We used data from four British longitudinal population-based studies (1946 NSHD, 1958 NCDS, 1970 BCS, and ELSA, N = 12,129). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the interrelationships between these experiences are elucidated in both periods. Results: Across the Four studies, prepandemic proportions reporting social isolation ranged from 15% to 54%, with higher rates in older ages (e.g., 32% of individuals aged 70-79 years and 54% of those more than 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The interrelationship between social isolation and loneliness did not change. Associations between sociodemographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with higher economic precarity (females, nonhomeowners, unemployed, illness, and greater financial stress). Discussion and Implications: There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening extent and inequalities in these. The concepts of loneliness and social isolation are not interchangeable, and clarity is needed in how they are conceptualized, operationalized, and interpreted. Given many older adults experience high levels of social isolation, there should be greater emphasis on reducing social isolation and the inequalities observed in who experiences greater isolation and loneliness.

9.
Data Brief ; 52: 109812, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38076473

RESUMO

This paper describes a dataset acquired from 41 volunteers performing 16 Activities of daily livings (ADLs) and 8 Falls repeated 5 times. This data was collected using a custom wrist-worn end device. The dataset has data collected from Inertial measurement unit (IMU) and heart-rate sensors. The end device is built using Qualcomm Snapdragon 820c System on Chip (SoC) interfaced to the sensors via Interconnect Integrated Circuit (I2C) protocol. The data was sampled for every activity at a rate of 20 Hz for the motion sensors and at a rate of 1 Hz for the heart-rate sensor. The motion sensor comprised of a triaxial accelerometer, triaxial gyroscope, triaxial magnetometer and a linear accelerometer. The heart-rate sensor was medical grade and all sensors were calibrated for the wrist -worn position. The dataset is available on this website https://shamanx86.github.io/fall_detection_data/ and https://doi.org/10.5281/zenodo.10013090.

10.
Small ; : e2306361, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38109121

RESUMO

Artificial van der Waals heterostructures, obtained by stacking two-dimensional (2D) materials, represent a novel platform for investigating physicochemical phenomena and applications. Here, the electrochemistry at the one-dimensional (1D) edge of a graphene sheet, sandwiched between two hexagonal boron nitride (hBN) flakes, is reported. When such an hBN/graphene/hBN heterostructure is immersed in a solution, the basal plane of graphene is encapsulated by hBN, and the graphene edge is exclusively available in the solution. This forms an electrochemical nanoelectrode, enabling the investigation of electron transfer using several redox probes, e.g., ferrocene(di)methanol, hexaammineruthenium, methylene blue, dopamine and ferrocyanide. The low capacitance of the van der Waals edge electrode facilitates cyclic voltammetry at very high scan rates (up to 1000 V s-1 ), allowing voltammetric detection of redox species down to micromolar concentrations with sub-second time resolution. The nanoband nature of the edge electrode allows operation in water without added electrolyte. Finally, two adjacent edge electrodes are realized in a redox-cycling format. All the above-mentioned phenomena can be investigated at the edge, demonstrating that nanoscale electrochemistry is a new application avenue for van der Waals heterostructures. Such an edge electrode will be useful for studying electron transfer mechanisms and the detection of analyte species in ultralow sample volumes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38109667

RESUMO

PURPOSE: To illustrate a patient with orbital compartment syndrome following scleral buckle placement that was successfully treated with canthotomy and cantholysis. METHODS: Observational case report. RESULTS: A 26-year-old male underwent a primary scleral buckle repair for a chronic rhegmatogenous retinal detachment. On post-operative day four, the patient presented to the emergency room with pain and increased intraocular pressure (IOP). Initial treatment with conservative IOP lowering agents was unsuccessful. The patient was diagnosed with delayed orbital compartment syndrome and was successfully managed with lateral canthotomy and inferior cantholysis in addition to aggressive steroid and antibiotic medical management. CONCLUSION: Following scleral buckle placement with sub-tenon's anesthesia block, there may be a delayed presentation of orbital compartment syndrome. Recognition and management of this rare complication is important for preventing irreversible blindness.

12.
Life (Basel) ; 13(10)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37895393

RESUMO

Artificial intelligence (AI) has been an important topic within radiology. Currently, AI is used clinically to assist with the detection of lesions through detection systems. However, a number of recent studies have demonstrated the increased value of neural networks in radiology. With an increasing number of screening requirements for cancers, this review aims to study the accuracy of the numerous AI models used in the detection and diagnosis of breast, lung, and prostate cancers. This study summarizes pertinent findings from reviewed articles and provides analysis on the relevancy to clinical radiology. This study found that whereas AI is showing continual improvement in radiology, AI alone does not surpass the effectiveness of a radiologist. Additionally, it was found that there are multiple variations on how AI should be integrated with a radiologist's workflow.

13.
Neuropharmacology ; 240: 109705, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37683886

RESUMO

Volatile anesthetics alter presynaptic function through effects on Ca2+ influx and neurotransmitter release. These actions are proposed to play important roles in their pleiotropic neurophysiological effects including immobility, unconsciousness and amnesia. Nitric oxide and cyclic guanosine monophosphate (NO/cGMP) signaling has been implicated in presynaptic mechanisms, and disruption of NO/cGMP signaling has been shown to alter sensitivity to volatile anesthetics in vivo. We investigated volatile anesthetic actions NO/cGMP signaling in relation to presynaptic function in cultured rat hippocampal neurons using pharmacological tools and genetically encoded biosensors and sequestering probes of cGMP levels. Using the fluorescent cGMP biosensor cGull, we found that electrical stimulation-evoked NMDA-type glutamate receptor-independent presynaptic cGMP transients were inhibited 33.2% by isoflurane (0.51 mM) and 26.4% by sevoflurane (0.57 mM) (p < 0.0001) compared to control stimulation without anesthetic. Stimulation-evoked cGMP transients were blocked by the nonselective inhibitor of nitric oxide synthase N-ω-nitro-l-arginine, but not by the selective neuronal nitric oxide synthase inhibitor N5-(1-imino-3-butenyl)-l-ornithine. Isoflurane and sevoflurane inhibition of stimulation-evoked increases in presynaptic Ca2+ concentration, measured with synaptophysin-GCaMP6f, and of synaptic vesicle exocytosis, measured with synaptophysin-pHlourin, was attenuated in neurons expressing the cGMP scavenger protein sponge (inhibition of exocytosis reduced by 54% for isoflurane and by 53% for sevoflurane). The anesthetic-induced reduction in presynaptic excitability was partially occluded by inhibition of HCN channels, a cGMP-modulated excitatory ion channel that can facilitate glutamate release. We propose that volatile anesthetics depress presynaptic cGMP signaling and downstream effectors like HCN channels that are essential to presynaptic function and excitability. These findings identify novel mechanisms by which volatile anesthetics depress synaptic transmission via second messenger signaling involving the NO/cGMP pathway in hippocampal neurons.


Assuntos
Anestésicos Inalatórios , Isoflurano , Ratos , Animais , Isoflurano/farmacologia , Sinaptofisina/metabolismo , Sevoflurano/farmacologia , Ratos Sprague-Dawley , Neurônios , Anestésicos Inalatórios/farmacologia , Ácido Glutâmico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Hipocampo , GMP Cíclico/farmacologia
14.
eNeuro ; 10(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37591734

RESUMO

Volatile anesthetics reduce excitatory synaptic transmission by both presynaptic and postsynaptic mechanisms which include inhibition of depolarization-evoked increases in presynaptic Ca2+ concentration and blockade of postsynaptic excitatory glutamate receptors. The presynaptic sites of action leading to reduced electrically evoked increases in presynaptic Ca2+ concentration and Ca2+-dependent exocytosis are unknown. Endoplasmic reticulum (ER) of Ca2+ release via ryanodine receptor 1 (RyR1) and uptake by SERCA are essential for regulation intracellular Ca2+ and are potential targets for anesthetic action. Mutations in sarcoplasmic reticulum (SR) release channels mediate volatile anesthetic-induced malignant hyperthermia (MH), a potentially fatal pharmacogenetic condition characterized by unregulated Ca2+ release and muscle hypermetabolism. However, the impact of MH mutations on neuronal function are unknown. We used primary cultures of postnatal hippocampal neurons to analyze volatile anesthetic-induced changes in ER Ca2+ dynamics using a genetically encoded ER-targeted fluorescent Ca2+ sensor in both rat and mouse wild-type (WT) neurons and in mouse mutant neurons harboring the RYR1 T4826I MH-susceptibility mutation. The volatile anesthetic isoflurane reduced both baseline and electrical stimulation-evoked increases in ER Ca2+ concentration in neurons independent of its depression of presynaptic cytoplasmic Ca2+ concentrations. Isoflurane and sevoflurane, but not propofol, depressed depolarization-evoked increases in ER Ca2+ concentration significantly more in mouse RYR1 T4826I mutant neurons than in wild-type neurons. The RYR1 T4826I mutant neurons also showed markedly greater isoflurane-induced reductions in presynaptic cytosolic Ca2+ concentration and synaptic vesicle (SV) exocytosis. These findings implicate RyR1 as a molecular target for the effects of isoflurane on presynaptic Ca2+ handling.


Assuntos
Isoflurano , Hipertermia Maligna , Ratos , Camundongos , Animais , Cálcio , Isoflurano/farmacologia , Hipertermia Maligna/genética , Canal de Liberação de Cálcio do Receptor de Rianodina , Roedores , Retículo Endoplasmático , Neurônios , Hipocampo
15.
BMJ Ment Health ; 26(1)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37562853

RESUMO

BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Saúde Mental , Pandemias , Registros Eletrônicos de Saúde , Ambiente Domiciliar , Estudos Prospectivos , Reino Unido/epidemiologia
16.
Retina ; 43(10): 1732-1737, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37267632

RESUMO

PURPOSE: Long-acting injectable steroids are changing the treatment paradigm for patients with chronic intraocular inflammation and cystoid macular edema (CME). We report the use of the fluocinolone implant 0.18 mg in patients with chronic postsurgical CME after pars plana vitrectomy. METHODS: This is a retrospective case series of 24 vitrectomized eyes which received fluocinolone implant for the management postsurgical CME. Clinical outcomes and requirement for rescue therapy were studied. RESULTS: Median length of follow-up was 19.3 months (range 8.3-23.2 months). There was an improvement in median central subfield thickness from 412 µ m (range 167-806 µ m) to 311 µ m (range 157-686 µ m) after fluocinolone implant ( P < 0.001). The injection burden decreased significantly after study treatment ( P < 0.001); however, there was no significant change in visual acuity ( P = 0.334). Eighteen eyes had control of CME that did not require additional intravitreal therapy. Four eyes had initially controlled but recurrent CME requiring intravitreal steroid therapy at median of 7.8 months (range 7.6-15.4 months). One eye never attained sufficient inflammatory control despite rescue therapy. CONCLUSION: Fluocinolone implant can be an effective treatment in vitrectomized patients with chronic postsurgical CME and can help decrease the overall injection burden.


Assuntos
Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Glucocorticoides , Estudos Retrospectivos , Fluocinolona Acetonida
17.
STAR Protoc ; 4(2): 102148, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37074907

RESUMO

Serine/threonine protein phosphatase 2 (PP2A) forms heterotrimeric holoenzymes, where a scaffold subunit bridges the PP2A catalytic subunit to a B regulatory subunit, e.g., B55α. The PP2A/B55α holoenzyme plays key roles in signaling and cell-cycle control targeting multiple substrates. Here, we describe semiquantitative approaches to determine PP2A/B55α substrate specificity. Parts I and II detail approaches to assess PP2A/B55α-mediated dephosphorylation of immobilized substrate peptide variants. Parts III and IV detail methods to assess PP2A/B55α-substrate-binding specificity. These approaches are adaptable to other serine/threonine phosphatases. For complete details on the use and execution of this protocol, please refer to Fowle et al..1.

18.
Life (Basel) ; 13(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37109491

RESUMO

The Coronavirus Disease 2019 (COVID-19) pandemic ushered in rapid changes in healthcare, including radiology, globally. This review discusses the impact of the pandemic on various radiology departments globally. We analyze the implications of the COVID-19 pandemic on the imaging volumes, finances, and clinical operations of radiology departments in 2020. Studies from health systems and outpatient imaging centers were analyzed, and the activity throughout 2020 was compared to the pre-pandemic activity, including activity during similar timeframes in 2019. Imaging volumes across modalities, including MRI and CT scans, were compared, as were the Relative Value Units (RVUs) for imaging finances. Furthermore, we compared clinical operations, including staffing and sanitation procedures. We found that imaging volumes in private practices and academic centers decreased globally. The decreases in volume could be attributed to delayed patient screenings, as well as the implementation of protocols, such as the deep cleaning of equipment between patients. Revenues from imaging also decreased globally, with many institutions noting a substantial decline in RVUs and revenue compared with pre-COVID-19 levels. Our analysis thus found significant changes in the volumes, finances, and operations of radiology departments due to the COVID-19 pandemic.

19.
Global Spine J ; : 21925682231170612, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081603

RESUMO

STUDY DESIGN: Retrospective Upright MRI Study. OBJECTIVES: Determine the relationship between lumbar disc herniation and presence of the nerve root sedimentation sign on upright kinematic MRI patients. METHODS: T2-weighted axial upright kMRI images of 100 patients with the presence of disc herniation in at least 1 lumbar disc between L1/L2 and L5/S1 were obtained. Sedimentation sign, spinal canal anterior-posterior (AP) diameter, disc height, disc herniation size, type of herniation, and zone of herniation were evaluated. A positive sedimentation sign was defined as having either the majority of nerve roots running ventrally or centrally in the canal or conglomeration of the nerve roots at the mid-disc level. Herniation types were defined as either no herniation, disc bulge, protrusion, extrusion, or sequestration. Zones of herniation were categorized as either central, lateral, or far lateral. RESULTS: The kappa value of intra-observer reliability was .915. The kappa value of disc levels with a negative sedimentation sign were seen more frequently (n = 326, 65.2%) than those with a positive sedimentation sign (n = 174, 34.8%). The spinal canal AP diameter was significantly decreased at the L3/L4 and L4/L5 level in patients with a positive sedimentation sign. Discs with a positive sedimentation sign had a larger average size of disc herniation compared to those with a negative sign at all levels. A relationship between positivity of the sedimentation sign and disc herniation type was significant at L2/L3, L3/L4, and L4/L5. CONCLUSIONS: Patients with a positive sedimentation sign were seen to have larger disc herniations and more severely degenerated discs.

20.
Cureus ; 15(3): e36342, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37082497

RESUMO

With an increasing global incidence in children younger than the age of five, respiratory syncytial virus (RSV) is one of the most common viral respiratory infections worldwide. Despite the increasing number of cases among infants and young children, RSV can infect any age group; however, some individuals are more high risk than others. Premature infants, young children, elderly, and immunocompromised individuals are the most likely to suffer a more severe presentation of RSV in comparison to healthy adults. RSV is transmitted through respiratory droplets via direct contact with an infected individual or with contaminated surfaces. The viral genome of RSV consists of 11 proteins. Out of these 11, two proteins allow for the attachment of the virus to the respiratory epithelial cells and fusion with host cells. Upon fusion, the viral material transfers to the host cell, where viral replication occurs. It is important to acknowledge that an individual is considered infectious and can transmit the virus even before the symptomatic presentation of RSV begins. As long as the individual is shedding the virus, he or she is considered infectious. The length of viral shedding also differs depending on the severity of the infection, who is infected, and the underlying immune status of an individual. Currently, there is no definitive treatment for RSV; however, supportive therapy is considered the mainstay treatment. Some pharmaceutical treatments such as ribavirin have been FDA-approved; however, the administration is typically limited to children and infants. Palivizumab is also administered as an immune prophylaxis; however, both therapies are constantly at the end of a cost-effective debate due to their extensively expensive nature and questionable adverse effect profiles. Supportive therapy includes hydration, supplemental oxygen, and mechanical ventilation in hospitalized cases; however, most RSV cases can be treated as outpatient cases. Prevention techniques such as hand washing and maintaining social distancing are imperative to minimize the transmission of the virus as much as remotely possible.

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