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2.
Artículo en Inglés | MEDLINE | ID: mdl-39292571

RESUMEN

Despite the development of numerous visual analytics tools for event sequence data across various domains, including but not limited to healthcare, digital marketing, and user behavior analysis, comparing these domain-specific investigations and transferring the results to new datasets and problem areas remain challenging. Task abstractions can help us go beyond domain-specific details, but existing visualization task abstractions are insufficient for event sequence visual analytics because they primarily focus on multivariate datasets and often overlook automated analytical techniques. To address this gap, we propose a domain-agnostic multi-level task framework for event sequence analytics, derived from an analysis of 58 papers that present event sequence visualization systems. Our framework consists of four levels: objective, intent, strategy, and technique. Overall objectives identify the main goals of analysis. Intents comprises five high-level approaches adopted at each analysis step: augment data, simplify data, configure data, configure visualization, and manage provenance. Each intent is accomplished through a number of strategies, for instance, data simplification can be achieved through aggregation, summarization, or segmentation. Finally, each strategy can be implemented by a set of techniques depending on the input and output components. We further show that each technique can be expressed through a quartet of action-input-output-criteria. We demonstrate the framework's descriptive power through case studies and discuss its similarities and differences with previous event sequence task taxonomies.

3.
Pediatr Emerg Care ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39173273

RESUMEN

ABSTRACT: Distal forearm fractures are frequently encountered in the pediatric emergency department and often require reduction. Procedural sedation is commonly used to facilitate reduction of these injuries, although it can be associated with potentially severe complications, particularly in patients with cardiorespiratory comorbidities. The ultrasound-guided hematoma block has been gaining popularity as an analgesic alternative in adult patients, but literature supporting its use in pediatric patients is limited. We describe a point-of-care ultrasound-guided hematoma block used to facilitate successful reduction of a distal radius fracture in an adolescent patient with a history of a difficult airway for whom procedural sedation would have posed considerable risk.

4.
J Arthroplasty ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39127311

RESUMEN

BACKGROUND: Cementless total knee arthroplasty (TKA) is rising in popularity. The literature supporting its use over cemented TKA remains sparse. Using the Canadian Joint Replacement Registry (CJRR), we sought to investigate cementless versus cemented fixation in modern primary TKA and (1) determine whether there is an overall difference in revision by fixation, (2) perform a subanalysis of the most-commonly used cementless TKA brand in Canada, and (3) identify the reasons for revision. METHODS: The CJRR data was used to analyze TKA designs with cemented and cementless versions. Revision risk is reported as all-cause cumulative percent revision (CPR). Reasons for revision were analyzed. Cox proportional hazards models were used to report adjusted hazard ratios (HR) controlling for age, sex, patella resurfacing, and bearing constraints. We included 202,880 primary TKAs performed between 2012 and 2021. Of those, 9,163 (4.5%) were cementless. RESULTS: The CPR at 8 years was 4.49% for cementless and 3.14% for cemented implants. After adjusting for confounders, we did not detect a difference in revision risk overall (HR 0.87 [95% CI (confidence interval) 0.73 to 1.04], P = 0.128). However, the most commonly used cementless TKA brand demonstrated a CPR of 1.95% compared to 2.19% for its cemented version at 4 years. Furthermore, we detected a significantly lower revision risk compared to its cemented version after adjusting for confounders (HR 0.66 [95% CI 0.51 to 0.85], P = 0.001). The 4 most common reasons for revision in both groups were the following: (1) infection, (2) instability, (3) aseptic loosening, and (4) pain of unknown origin. CONCLUSIONS: Using CJRR data adjusted for confounding factors, no difference in revision risk was detected between cemented and cementless implants overall. However, for the most common brand of cementless TKA used in Canada, there was a lower risk of revision than its corresponding cemented version. The reasons for revision were similar.

5.
Can J Surg ; 67(4): E300-E305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39089818

RESUMEN

BACKGROUND: Patients aged 40-60 years who require total hip arthroplasty (THA) often first receive unindicated hip arthroscopy or magnetic resonance imaging (MRI). Our objective was to identify potentially inappropriate resource utilization before THA, specifically reporting on the proportion of patients aged 40-60 years who underwent hip arthroscopy or MRI in the year before THA. METHODS: We conducted a retrospective, population-based study at the provincial level. We retrieved data from the Canadian Institute for Health Information (CIHI). We included all Ontario residents who underwent an elective, primary THA for osteoarthritis between Apr. 1, 2004, and Mar. 31, 2016. We identified the rates and timing of patients who underwent an MRI or hip arthroscopy before their index THA. RESULTS: The percentage of patients who underwent an MRI before THA increased significantly over the study period, from 8.7% in 2004 to 23.8% in 2015. There was also a significant but variable trend in the percentage of patients who underwent a hip arthroscopy before THA. CONCLUSION: Our results demonstrate a high, gradually increasing proportion of patients who received a hip MRI and a low but increasing proportion of patients who received hip arthroscopy in close proximity to THA. Multidisciplinary collaboration may improve knowledge translation and help reduce the rate of clinically unnecessary diagnostic and therapeutic interventions in this population of patients who require THA.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroscopía , Imagen por Resonancia Magnética , Osteoartritis de la Cadera , Procedimientos Innecesarios , Humanos , Osteoartritis de la Cadera/cirugía , Persona de Mediana Edad , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Estudios Retrospectivos , Adulto , Femenino , Artroscopía/estadística & datos numéricos , Masculino , Ontario , Procedimientos Innecesarios/estadística & datos numéricos
6.
Orthop J Sports Med ; 12(8): 23259671241258429, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157023

RESUMEN

Background: Selecting an appropriate graft for anterior cruciate ligament (ACL) reconstruction requires consideration of a patient's preferences, goals, age, and physical demands alongside the risks and benefits of each graft choice. Purpose: To determine the most popular ACL reconstruction grafts among patients and the most important factors influencing their decisions. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients undergoing ACL reconstruction between October 2022 and April 2023 completed a survey either before (nonconsult group) or after (consult group) speaking with their surgeon, who provided an evidence-based description of the pros and cons of an allograft and the following autografts: bone-patellar tendon-bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT). Patient characteristics, graft choice, information influencing their graft choice, and surgeon recommendation were collected and compared between the groups. Results: Among the 100 included patients, 59.0% were male, and the mean age was 28.3 ± 10.4 years. The most popular grafts were the BPTB (56.0%), followed by the QT (29.0%), HT (8.0%), and allograft (7.0%). No significant difference was observed in the graft selection between the consult group (n = 60; BPTB, 46.7%; QT, 38.3%; HT, 8.3%; allograft, 6.7%) and nonconsult group (n = 40; BPTB, 70.0%; QT, 15.0%; HT, 7.5%; allograft, 7.5%) (P = .0757). In the consult group, 81.7% of patients selected the graft recommended to them by their surgeon. The top 2 graft selection reasons were usage in professional athletes and failure rates, while the top 2 ACL surgery concerns were returning to their desired level of athletics and graft failure risk. Among the 93 patients who researched their ACL graft options before their visit, the most popular information source was some form of media (72.0% [67/93]). Conclusion: The study findings underscore the importance of patient preference and surgeon recommendation in a patient's graft selection and highlight the need to be cognizant of the information sources available to patients when researching their graft options.

7.
Arthroplast Today ; 27: 101420, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38966329

RESUMEN

Background: Although there have been several studies describing risk factors for complications after outpatient total hip arthroplasty (THA), data describing the timing of such complications is lacking. Methods: Patients who underwent outpatient or inpatient primary THA were identified in the 2012-2019 National Surgical Quality Improvement Program database. For 9 different 30-day complications, the median postoperative day of diagnosis was determined. Multivariable regressions were used to compare the risk of each complication between outpatient vs inpatient groups. Multivariable Cox proportional hazards modeling was used to evaluate the differences in the timing of each adverse event between the groups. Results: After outpatient THA, the median day of diagnosis for readmission was 12.5 (interquartile range 5-22), surgical site infection 15 (2-21), urinary tract infection 13.5 (6-19.5), deep vein thrombosis 13 (8-21), myocardial infarction 4.5 (1-7), pulmonary embolism 15 (8-25), sepsis 16 (9-26), stroke 2 (0-7), and pneumonia 6.5 (3-10). On multivariable regressions, outpatients had a lower relative risk (RR) of readmission (RR = 0.73), surgical site infection (RR = 0.72), and pneumonia (RR = 0.1), all P < .05. On multivariable cox proportional hazards modeling, there were no statistically significant differences in the timing of each complication between outpatient vs inpatient procedures (P > .05). Conclusions: The timing of complications after outpatient THA was similar to inpatient procedures. Consideration should be given to lowering thresholds for diagnostic testing after outpatient THA for each complication during the at-risk time periods identified here. Although extremely rare, this is especially important for catastrophic adverse events, which tend to occur early after discharge.

8.
Front Allergy ; 5: 1417879, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076462

RESUMEN

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

9.
Arthroscopy ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38395270

RESUMEN

PURPOSE: To report return-to-sport rates, postoperative patient-reported outcomes (PROs), complication rates, and reoperation rates of a cohort of patients undergoing particulated juvenile articular cartilage (PJAC) allograft transplantation for patellofemoral articular cartilage defects. METHODS: We performed a single-institution retrospective review of all patients with patellofemoral articular cartilage defects who received PJAC allograft transplantation from 2014 to 2022. Baseline demographic characteristics and surgical data, including concomitant surgical procedures, were collected. Clinical outcomes recorded included return-to-sport rates, complications, reoperations, and the following PRO scores: Kujala knee score, Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference score, and PROMIS Physical Function score. RESULTS: Forty-one knees with a mean age of 23.4 ± 9.7 years and mean follow-up period of 30.3 months (range, 12-107 months) were included. The mean postoperative PROMIS Pain Interference, PROMIS Physical Function, and Kujala knee scores were 47.4 ± 7.7, 52.2 ± 10.8, and 81.7 ± 16.1, respectively, reflecting low residual anterior knee pain and a return to normal function. For patients playing organized sports at the high school and collegiate levels, the overall return-to-sport rate was 100% (17 of 17). During follow-up, complications developed in 12 knees (29.3%), the most common of which was anterior-based knee pain, and 6 knees (14.6%) required a total of 8 reoperations, which occurred from 6 to 32 months postoperatively. CONCLUSIONS: The 100% return-to-sport rate and satisfactory PRO scores in our study suggest that PJAC allograft transplantation can effectively address patellofemoral cartilage defects in many patients. The complication and reoperation rates of 29.3% and 14.6%, respectively, are consistent with the challenging and heterogeneous etiology and treatment of patellofemoral articular defects. LEVEL OF EVIDENCE: Level IV, case series.

10.
Arthroplast Today ; 25: 101285, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38261888

RESUMEN

Background: During the initial coronavirus pandemic lockdown period, remote hip and knee arthroplasty care was heavily employed out of necessity. However, data on patient satisfaction with telemedicine specific to hip and knee arthroplasty patients remains unknown. Methods: All patients who had a telemedicine visit in the hip and knee arthroplasty department and completed a telemedicine satisfaction survey at a specialty hospital from April 1, 2020, to December 31, 2020, were identified. Patient satisfaction with telemedicine, gauged through a series of questions, were analyzed and evaluated over time. Independent factors associated with high satisfaction, defined as the "Top Box" response to the survey question "Likelihood of your recommending our video visit service to others," were identified. Results: Overall, 29,003 patients who had an in-person or telemedicine visit in the hip and knee arthroplasty department during the study period were identified. During the initial coronavirus pandemic lockdown period, defined as April 1, 2020-May 31, 2020, rate of overall telemedicine utilization was approximately 84%. After the initial lockdown period, the rate of overall telemedicine utilization was approximately 8% of all visits per month. Average satisfaction scores for a series of 14 questions were consistently above 4.5 out of 5. Multivariable regression revealed younger age, particularly 18-64 years old, to be the only independent factor associated with high satisfaction with telemedicine. The rate of high satisfaction remained statistically similar throughout the study period (P > .05). Conclusions: Patient satisfaction with telemedicine was consistently high in various domains and remained high throughout the study period, regardless of loosened pandemic restrictions. This technology will most likely continue to be utilized, but perhaps it should be targeted at patients younger than 65 years of age.

11.
Spine (Phila Pa 1976) ; 49(3): 208-213, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36856548

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objectives of the present study were to (1) define telemedicine utilization rates during and after the initial height of the COVID-19 lockdown period and (2) determine patient satisfaction with telemedicine during and after the initial height of the COVID-19 lockdown period for spine patients at an orthopedic specialty hospital. SUMMARY OF BACKGROUND DATA: Previous studies have shown high patient satisfaction with telemedicine during the initial height of the COVID-19 pandemic. However, there exists limited data about spine telemedicine utilization and patient satisfaction after the reopening of in-person office visits and the easing of restrictions on elective surgical care. MATERIALS AND METHODS: All patients who had an in-person or telemedicine visit at an urban tertiary specialty hospital from April 1, 2020 to April 15, 2021 were identified. Rates of overall telemedicine utilization over time were delineated. Patient satisfaction with telemedicine, as assessed through a series of questionnaires, was also evaluated over time. RESULTS: Overall, 60,368 patients were identified. Of these, 19,568 patients (32.4%) had telemedicine visit. During the peak initial coronavirus lockdown period, the rate of overall telemedicine utilization, on average, was greater than 90%. After the peak period, the rate of overall telemedicine utilization on average was at ~29% of all visits per month. The percentage of patients who would have been definitely comfortable if the telemedicine visit had been in-person increased over the entire study period ( P <0.001). Despite this, patient satisfaction based on survey responses remained statistically similar throughout the study period ( P >0.05). CONCLUSION: The rate of telemedicine utilization in spine patients remains high, at ~one-third of all visits, even after the initial peak coronavirus lockdown period. In addition, patient satisfaction with telemedicine remained consistent throughout the study period, regardless of pandemic restrictions on in-person visits. LEVEL OF EVIDENCE: 3.


Asunto(s)
COVID-19 , Telemedicina , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Pandemias , Satisfacción del Paciente , Control de Enfermedades Transmisibles , Satisfacción Personal
12.
J Virol ; 97(12): e0133023, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37966249

RESUMEN

IMPORTANCE: The essential steps of successful gene delivery by recombinant adeno-associated viruses (rAAVs) include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.


Asunto(s)
Bronquios , Dependovirus , Epitelio , Técnicas de Transferencia de Gen , Vectores Genéticos , Transducción Genética , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , ADN , Epitelio/metabolismo , Epitelio/virología , Técnicas de Transferencia de Gen/tendencias , Terapia Genética/métodos , Vectores Genéticos/genética , Bronquios/metabolismo , Bronquios/virología , Transporte Activo de Núcleo Celular , Edición Génica/tendencias
13.
J Clin Ultrasound ; 51(9): 1622-1630, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37850556

RESUMEN

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.


Asunto(s)
Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Estados Unidos , Humanos , Ultrasonografía , Habilitación Profesional
14.
bioRxiv ; 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37808760

RESUMEN

Recombinant (r)AAV2.5T was selected from the directed evolution of an AAV capsid library in human airway epithelium (HAE). The capsid gene of rAAV2.5T is a chimera of the N-terminal unique coding sequence of AAV2 VP1 unique (VP1u) and the VP2- and VP3-coding sequence of AAV5 with a single amino acid mutation of A581T. We conducted two rounds of genome wide CRISPR gRNA library screening for host factors limiting rAAV2.5T transduction in HeLa S3 cells. The screen identified several genes that are critical for rAAV2.5T transduction in HeLa S3 cells, including previously reported genes KIAA0319L , TM9SF2 , VPS51 , and VPS54 , as well as a novel gene WDR63 . We verified the role of KIAA0319L and WDR63 in rAAV2.5T transduction of polarized HAE by utilizing CRISPR gene knockouts. Although KIAA0319L, a proteinaceous receptor for multiple AAV serotypes, played an essential role in rAAV2.5T transduction of polarized HAE either from apical or basolateral side, our findings demonstrated that the internalization of rAAV2.5T was independent of KIAA0319L. Importantly, we confirmed WDR63 is an important player in rAAV2.5T transduction of HAE, while not being involved in vector internalization and nuclear entry. Furthermore, we identified that the basal stem cells of HAE can be significantly transduced by rAAV2.5T. Significance: The essential steps of a successful gene delivery by rAAV include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63 , whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.

16.
bioRxiv ; 2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37163096

RESUMEN

A single gene may be regulated by multiple enhancers, but how they work in concert to regulate transcription is poorly understood. Prior studies have mostly examined enhancers at single loci and have reached inconsistent conclusions about whether epistatic-like interactions exist between them. To analyze enhancer interactions throughout the genome, we developed a statistical framework for CRISPR regulatory screens that utilizes negative binomial generalized linear models that account for variable guide RNA (gRNA) efficiency. We reanalyzed a single-cell CRISPR interference experiment that delivered random combinations of enhancer-targeting gRNAs to each cell and interrogated interactions between 3,808 enhancer pairs. We found that enhancers act multiplicatively with one another to control gene expression, but our analysis provides no evidence for interaction effects between pairs of enhancers regulating the same gene. Our findings illuminate the regulatory behavior of multiple enhancers and our statistical framework provides utility for future analyses studying interactions between enhancers.

17.
J Arthroplasty ; 38(7S): S83-S88.e2, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37100095

RESUMEN

BACKGROUND: Contemporary total hip arthroplasty (THA) has resolved many implant longevity concerns in younger patients. Patients in their fourth and fifth decades of life are projected to be the fastest-growing demographic of THA patients. We aimed to assess this demographic to: 1) evaluate the rate of THA over time; 2) evaluate the cumulative incidence of revision; and 3) identify risk factors for revision. METHODS: A retrospective population-based study of patients between 40 and 60 years old undergoing primary THA was conducted using administrative data from a large clinical data repository. A total of 28,414 patients were included for analysis with a mean age of 53 years (range, 40-60 years) and median follow-up of 9 years (range, 0-17 years). Linear regressions were used to assess annual rates of THA in this cohort over time. Kaplan-Meier analysis was used to determine cumulative incidence of revision. Multivariate Cox proportional hazards models were used to determine association of variables with revision risk. RESULTS: The annual rate of THA in our population increased by 60.7% over the study period (P < .0001). Cumulative incidence of revision was 2.9% at 5 years and 4.8% at 10 years. Younger age, women, non-osteoarthritis diagnosis, medical complications, and annual surgeon volume ≤ 60 THA were associated with increased revision risk. CONCLUSION: Demand for THA continues to dramatically increase in this cohort. Risk of revision was low but multiple risk factors were identified. Future studies will help delineate the effect of these variables on revision risk and assess implant survivorship beyond 10 years.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Humanos , Femenino , Persona de Mediana Edad , Adulto , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Estudios Retrospectivos , Falla de Prótesis , Reoperación/efectos adversos , Factores de Riesgo , Diseño de Prótesis , Resultado del Tratamiento
18.
Am J Hum Genet ; 110(4): 703-714, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36990085

RESUMEN

GATA3 is essential for T cell differentiation and is surrounded by genome-wide association study (GWAS) hits for immune traits. Interpretation of these GWAS hits is challenging because gene expression quantitative trait locus (eQTL) studies lack power to detect variants with small effects on gene expression in specific cell types and the genome region containing GATA3 contains dozens of potential regulatory sequences. To map regulatory sequences for GATA3, we performed a high-throughput tiling deletion screen of a 2 Mb genome region in Jurkat T cells. This revealed 23 candidate regulatory sequences, all but one of which is within the same topological-associating domain (TAD) as GATA3. We then performed a lower-throughput deletion screen to precisely map regulatory sequences in primary T helper 2 (Th2) cells. We tested 25 sequences with ∼100 bp deletions and validated five of the strongest hits with independent deletion experiments. Additionally, we fine-mapped GWAS hits for allergic diseases in a distal regulatory element, 1 Mb downstream of GATA3, and identified 14 candidate causal variants. Small deletions spanning the candidate variant rs725861 decreased GATA3 levels in Th2 cells, and luciferase reporter assays showed regulatory differences between its two alleles, suggesting a causal mechanism for this variant in allergic diseases. Our study demonstrates the power of integrating GWAS signals with deletion mapping and identifies critical regulatory sequences for GATA3.


Asunto(s)
Elementos de Facilitación Genéticos , Factor de Transcripción GATA3 , Hipersensibilidad , Secuencias Reguladoras de Ácidos Nucleicos , Linfocitos T , Humanos , Alelos , Factor de Transcripción GATA3/genética , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Hipersensibilidad/genética , Mapeo Cromosómico , Eliminación de Gen
19.
Sci Adv ; 9(2): eade0869, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36630517

RESUMEN

Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5-68 of minor capsid protein VP1 (VP1u5-68aa) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs. AXL gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity (KD = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.


Asunto(s)
Tirosina Quinasa del Receptor Axl , Eritema Infeccioso , Parvovirus B19 Humano , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Eritema Infeccioso/metabolismo , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/metabolismo , Unión Proteica , Tirosina Quinasa del Receptor Axl/metabolismo
20.
Am J Sports Med ; 51(10): 2758-2765, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-35749344

RESUMEN

BACKGROUND: Individual studies reporting the clinical outcomes of arthroscopic bony Bankart repair for anterior shoulder instability have reported excellent results but have been limited by their small sample sizes. No systematic review of the literature has been performed examining the clinical outcomes of arthroscopic bony Bankart repair. PURPOSE: To provide a systematic review of the literature to examine the functional outcomes, recurrence rate, and return to sports rate after arthroscopic bony Bankart repair for anterior instability of the shoulder. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the literature based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted using the Cochrane Database of Systematic Reviews, Ovid/Embase, PubMed, and Web of Science. Studies that examined clinical outcomes after arthroscopic bony Bankart repair for anterior shoulder instability were included. Data pertaining to study characteristics and design, patient demographic characteristics, and clinical results, including functional outcomes, recurrence rate, and return to sports, were collected. The results from the studies were pooled, and weighted means and overall rates were calculated. RESULTS: In total, 21 studies with 769 patients were included for analysis. Most patients were male (91.7%), the mean age was 26.7 years (range, 12-71 years), and the mean follow-up was 42.7 months (range, 6-120 months). The most commonly reported functional outcome score was the Rowe score (12 studies), which improved on average from 41.9 preoperatively to 90.8 postoperatively. The rate of recurrent instability was reported by all 21 studies, and the overall recurrence rate was 11.9% (88/738). Return to sports after arthroscopic bony Bankart repair was reported by 11 studies, with a pooled return to sports rate of 91.0% (264/290). CONCLUSION: Arthroscopic bony Bankart repair for anterior shoulder instability resulted in improvements in functional outcomes, a low rate of recurrent instability, and a high rate of return to sports. Although these findings are extremely promising, future prospective studies with larger sample sizes are needed to further evaluate the clinical outcomes of arthroscopic bony Bankart repair.


Asunto(s)
Lesiones de Bankart , Inestabilidad de la Articulación , Luxación del Hombro , Articulación del Hombro , Humanos , Masculino , Adulto , Femenino , Hombro , Articulación del Hombro/cirugía , Luxación del Hombro/cirugía , Inestabilidad de la Articulación/cirugía , Estudios Prospectivos , Artroscopía/métodos , Recurrencia , Estudios Retrospectivos , Lesiones de Bankart/cirugía
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