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2.
Ophthalmol Glaucoma ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697359

RESUMEN

PURPOSE: To compare surgical outcomes of phacoemulsification combined with Baerveldt implantation (phaco-tube) or trabeculectomy with mitomycin-C (MMC) (phaco-trab) in patients without prior incisional ocular surgery. DESIGN: Single-center, retrospective, comparative case series. PARTICIPANTS: A total of 90 patients underwent surgical treatment, including 45 patients in the phaco-tube group and 45 patients in the phaco-trab group. METHODS: Eligible patients were identified using current procedural terminology (CPT) codes, and their medical records were retrospectively reviewed. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of surgical failure (IOP ≤5 mmHg or >21 mmHg or reduced <20% from baseline on 2 consecutive study visits after 3 months, reoperations for glaucoma, or experienced loss of light perception vision). Patients who had successful surgical outcomes without use of glaucoma medications were classified as complete successes, while those who used glaucoma medications were classified as qualified successes. Secondary outcome measures were visual acuity (VA), visual field mean deviation (VFMD), intraocular pressure (IOP), glaucoma medication use, and complications. RESULTS: The cumulative probability of failure was 6.7% in the phaco-tube group and 32.8% in the phaco-trab group after 3 years (P = 0.005; Restricted Mean Survival Time = 5.9 months, 95% CI = 1.4-10.4 months). The IOP was 13.1 ± 3.4 mmHg in the phaco-tube group and 13.3 ± 6.2 mmHg in the phaco-trab group at 3 years (P = 0.90), and the number of glaucoma medications was 2.6 ± 1.5 in the phaco-tube group and 1.7 ± 1.3 in the phaco-trab group (P = 0.015). The logarithm of the minimum angle of resolution VA was 0.39 ± 0.58 in the phaco-tube group and 0.43 ± 0.73 in the phaco-trab group at 3 years (P = 0.82), and VFMD was -18.3 ± 9.0 dB in the phaco-tube group and -14.1 ± 7.0 dB in the phaco-trab group (P = 0.16). Postoperative complications developed in 21 patients (47%) in the phaco-tube group and 15 patients (33%) in the phaco-trab group (P = 0.28). CONCLUSIONS: Phaco-tubes had a significantly lower rate of surgical failure compared to phaco-trabs after 3 years of follow-up. However, phaco-trabs used significantly fewer glaucoma medications at multiple postoperative timepoints and had a higher proportion of complete success. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

3.
Ophthalmol Retina ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38641006

RESUMEN

PURPOSE: Swept-source OCT angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross sectional and en face imaging strategies. DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30, 2022. PARTICIPANTS: Patients with AMD. METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. MAIN OUTCOME MEASURES: Swept-source OCT angiography imaging of AMD at different stages of disease progression. RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

4.
bioRxiv ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38405733

RESUMEN

During cell movement, cortical actin balances mechanical and osmotic forces to maintain cell function while providing the scaffold for cell shape. Migrating CD4+ T cells have a polarized structure with a leading edge containing dynamic branched and linear F-actin structures that bridge intracellular components to surface adhesion molecules. These actin structures are complemented with a microtubular network beaded with membrane bound organelles in the trailing uropod. Disruption of actin structures leads to dysregulated migration and changes in morphology of affected cells. In HIV-1 infection, CD4+ T cells have dysregulated movement. However, the precise mechanisms by which HIV-1 affects CD4+ T cell movement are unknown. Here, we show that HIV-1 infection of primary CD4+ T cells causes at least four progressive morphological differences as a result of virally induced cortical cytoskeleton disruption, shown by ultrastructural and time lapse imaging. Infection with a ΔNef virus partially abrogated the dysfunctional phenotype in infected cells and partially restored a wild-type shape. The pathological morphologies after HIV-1 infection phenocopy leukocytes which contain genetic determinants of specific T cell Inborn Errors of Immunity (IEI) or Primary Immunodeficiencies (PID) that affect the actin cytoskeleton. To identify potential actin regulatory pathways that may be linked to the morphological deformities, uninfected CD4+ T cell morphology was characterized following addition of small molecule chemical inhibitors. The ARP2/3 inhibitor CK-666 recapitulated three of the four abnormal morphologies we observed in HIV-1 infected cells. Restoring ARP2/3 function and cortical actin integrity in people living with HIV-1 infection is a new avenue of investigation to eradicate HIV-1 infected cells from the body.

5.
Am J Prev Med ; 66(6): 999-1007, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38311192

RESUMEN

INTRODUCTION: This study develops a practical method to triage Army transitioning service members (TSMs) at highest risk of homelessness to target a preventive intervention. METHODS: The sample included 4,790 soldiers from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in 1 of 3 Army STARRS 2011-2014 baseline surveys followed by the third wave of the STARRS-LS online panel surveys (2020-2022). Two machine learning models were trained: a Stage-1 model that used administrative predictors and geospatial data available for all TSMs at discharge to identify high-risk TSMs for initial outreach; and a Stage-2 model estimated in the high-risk subsample that used self-reported survey data to help determine highest risk based on additional information collected from high-risk TSMs once they are contacted. The outcome in both models was homelessness within 12 months after leaving active service. RESULTS: Twelve-month prevalence of post-transition homelessness was 5.0% (SE=0.5). The Stage-1 model identified 30% of high-risk TSMs who accounted for 52% of homelessness. The Stage-2 model identified 10% of all TSMs (i.e., 33% of high-risk TSMs) who accounted for 35% of all homelessness (i.e., 63% of the homeless among high-risk TSMs). CONCLUSIONS: Machine learning can help target outreach and assessment of TSMs for homeless prevention interventions.


Asunto(s)
Personas con Mala Vivienda , Aprendizaje Automático , Personal Militar , Humanos , Personas con Mala Vivienda/estadística & datos numéricos , Personal Militar/estadística & datos numéricos , Masculino , Estados Unidos , Adulto , Femenino , Estudios Longitudinales , Adulto Joven , Prevalencia , Encuestas y Cuestionarios
6.
Ophthalmol Sci ; 4(3): 100424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38284102

RESUMEN

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

7.
Cell Stem Cell ; 31(2): 196-211.e6, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38237586

RESUMEN

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.


Asunto(s)
COVID-19 , Células Madre Pluripotentes , Humanos , SARS-CoV-2 , Neuronas Dopaminérgicas , Sistema Nervioso Central
8.
Arthroscopy ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38266743

RESUMEN

PURPOSE: To intraoperatively evaluate the ability of anterior cruciate ligament (ACL) primary repair (ACLPR) to restore anterior tibial translation (ATT) at time zero and to assess the influence of additional suture augmentation (SA) on ATT. METHODS: Patients with proximal ACL tears undergoing arthroscopic ACLPR with dual-suture anchor fixation were included in this time-zero clinical study. Laxity measurements were taken with a digital arthrometer to evaluate ATT stability preoperatively in the office (T0) as a standardized diagnostic tool, preoperatively under anesthesia (T1), at time zero intraoperatively after ACLPR but prior to SA fixation (T2), and after SA fixation (T3). RESULTS: A total of 27 patients (mean age ± standard deviation [SD], 35.1 ± 12.0 years) with proximal ACL tears and significant preoperative (T0) ATT side-to-side differences (SSDs) (mean ± SD, 4.1 ± 1.5 mm) were evaluated. ACLPR was shown to restore ATT SSD at time zero (mean ± SD, 0.2 ± 1.1 mm) given that a significant reduction in ATT SSD (mean difference ± standard error, -4.7 ± 0.21 mm; P < .001) was achieved when comparing preoperative and intraoperative measurements after separate refixation of both ACL bundles with suture anchors. Additional SA fixation did not further decrease ATT when comparing measurements of the ipsilateral leg after ACL refixation and after SA fixation (mean difference ± SD, 0.03 ± 0.22 mm; P = .496). CONCLUSIONS: ACLPR with dual-suture anchor fixation restores time-zero ATT laxity in adults with proximal ACL tears. Additional SA fixation in full knee extension does not further decrease ATT. CLINICAL RELEVANCE: This study provides important information about the effectiveness of ACLPR in restoring ATT. SA with the knee fixed in full knee extension does not further decrease ATT; therefore, augmentation may not lead to overconstraint of the knee or stress shielding of the repaired ACL.

9.
J Glaucoma ; 33(1): 15-23, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37647317

RESUMEN

PRCIS: Monitoring visual fields (VFs) through virtual reality devices proved to have good inter-test and test-retest reliability, as well as easy usability, when self-administered by individuals with and without VF defects in a remote setting. PURPOSE: To assess the reliability of remote, self-administered VF monitoring using a virtual reality VF (VRVF) device in individuals without ocular disease and with stable VF defects. MATERIALS AND METHODS: Individuals without ocular disease and with stable defects were recruited. All participants had a baseline standard automated perimetry (SAP) test. Participants tested remotely on a VRVF device for 4 weeks (examinations V 1 , V 2 , V 3 , and V 4 ), with the last 3 unassisted. The mean sensitivities of VRVF results were compared with each other and to SAP results for reliability. RESULTS: A total of 42 eyes from 21 participants were tested on the VRVF device. Participants tested consistently although external factors impacted outcomes. VRVF results were in reasonable agreement with the baseline SAP. Examinations performed by the cohort with stable defects evinced better agreement with SAP examinations (V2, P = 0.79; V3, P = 0.39; V4, P = 0.35) than those reported by the cohort without ocular disease (V2, P = 0.02; V3, P = 0.15; V4, P = 0.22), where the null hypothesis is that the instruments agree. Fixation losses were high and variable in VRVF examinations compared with those of SAP, particularly in certain test takers. Participants considered the device comfortable and easy to use. CONCLUSIONS: Self-administered, remote VF tests on a VRVF device showed satisfactory test-retest reliability, good inter-test agreement with SAP, and acceptability by its users. External factors may impact at-home testing and age and visual impairment may hinder fixation. Future studies to expand the sample size and understand inconsistencies in fixation losses are recommended.


Asunto(s)
Telemedicina , Baja Visión , Humanos , Pruebas del Campo Visual/métodos , Campos Visuales , Proyectos Piloto , Reproducibilidad de los Resultados , Presión Intraocular , Estudios Prospectivos , Trastornos de la Visión/diagnóstico
10.
Ophthalmol Retina ; 8(1): 62-71, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37531996

RESUMEN

PURPOSE: Patients with clinically significant carotid artery stenosis (CAS) undergoing carotid artery endarterectomy (CEA) were imaged with swept-source OCT angiography (SS-OCTA) imaging protocol to determine if there were changes in choroidal blood flow after surgery. DESIGN: Prospective observational study. PARTICIPANTS: Patients with clinically significant CAS undergoing unilateral CEA. METHODS: All participants underwent SS-OCTA imaging using a 6 × 6-mm scan pattern on both eyes before CEA and within 1 week after CEA. Previously validated automated algorithms were used to measure the mean choroidal thickness (MCT) and choroidal vascular index (CVI) within 2.5-mm and 5-mm circles centered on the fovea. Multivariable regression analysis was conducted to evaluate the impact of various baseline factors including age, mean arterial blood pressure, and degree of stenosis, on both baseline of MCT and CVI, and the changes in MCT and CVI. MAIN OUTCOME MEASURES: Changes in MCT and CVI. RESULTS: One hundred sixteen eyes from 60 patients with a mean age of 71.57 ± 7.37 years were involved in the study. At baseline, MCT in both the 2.5-mm and 5-mm circles was significantly thinner on the surgical side compared with the nonsurgical side (P = 0.03), while no significant differences were seen in the CVI at baseline between the 2 sides (2.5-mm circle: P = 0.24; 5-mm circle: P = 0.09). Within 1 week after CEA, there were significant increases in the MCT on the surgical side, as compared with the nonsurgical side, in both the 2.5-mm (P < 0.001) and the 5-mm (P < 0.001) circles. No significant change in mean CVI was noted before and after CEA on the surgical side versus the nonsurgical side (2.5-mm circle: P = 0.30; 5-mm circle: P = 0.97). Multivariable regression analysis revealed that baseline MCT before CEA significantly decreased with age on both the surgical (P < 0.001) and nonsurgical sides (P = 0.003) while the changes in MCT and CVI after CEA were not associated with age, mean arterial blood pressure, or degree of stenosis. CONCLUSION: A rapid and significant increase in MCT was observed on the ipsilateral side of CEA, suggesting an improvement in choroidal perfusion within 1 week after surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Humanos , Persona de Mediana Edad , Anciano , Constricción Patológica , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/cirugía , Fóvea Central , Perfusión
11.
Soc Psychiatry Psychiatr Epidemiol ; 59(2): 261-271, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37291331

RESUMEN

BACKGROUND: Identifying predictors of suicidal ideation (SI) is important to inform suicide prevention efforts, particularly among high-risk populations like military veterans. Although many studies have examined the contribution of psychopathology to veterans' SI, fewer studies have examined whether experiencing good psychosocial well-being with regard to multiple aspects of life can protect veterans from SI or evaluated whether SI risk prediction can be enhanced by considering change in life circumstances along with static factors. METHODS: The study drew from a longitudinal population-based sample of 7141 U.S. veterans assessed throughout the first three years after leaving military service. Machine learning methods (cross-validated random forests) were applied to examine the predictive utility of static and change-based well-being indicators to veterans' SI, as compared to psychopathology predictors. RESULTS: Although psychopathology models performed better, the full set of well-being predictors demonstrated acceptable discrimination in predicting new-onset SI and accounted for approximately two-thirds of cases of SI in the top strata (quintile) of predicted risk. Greater engagement in health promoting behavior and social well-being were most important in predicting reduced SI risk, with several change-based predictors of SI identified but stronger associations observed for static as compared to change-based indicator sets as a whole. CONCLUSIONS: Findings support the value of considering veterans' broader well-being in identifying individuals at risk for suicidal ideation and suggest the possibility that well-being promotion efforts may be useful in reducing suicide risk. Findings also highlight the need for additional attention to change-based predictors to better understand their potential value in identifying individuals at risk for SI.


Asunto(s)
Ideación Suicida , Veteranos , Humanos , Veteranos/psicología , Factores de Riesgo , Prevención del Suicidio , Psicopatología
12.
Clin Exp Ophthalmol ; 52(1): 10-21, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37953685

RESUMEN

BACKGROUND: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.


Asunto(s)
Síndromes de Ojo Seco , Síndrome de Fatiga Crónica , Veteranos , Humanos , Masculino , Estados Unidos/epidemiología , Persona de Mediana Edad , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/epidemiología , Estudios Transversales , Estudios Prospectivos , Guerra del Golfo , Canadá , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/epidemiología , Dolor
13.
Invest Ophthalmol Vis Sci ; 64(15): 42, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38153750

RESUMEN

Purpose: The impact of carotid endarterectomy (CEA) on choriocapillaris (CC) perfusion was investigated using swept-source optical coherence tomography angiography (SS-OCTA) imaging before and after surgery in patients with clinically significant carotid artery stenosis (CAS). Methods: In this prospective observational study, patients with clinically significant CAS undergoing unilateral CEA had SS-OCTA imaging performed in both eyes before and within 1 week after surgery. The percent CC flow deficits (CC FD%) and CC thickness were assessed using previously validated algorithms. Multivariable regression analysis was conducted to evaluate the impact of variables on the change in CC measurements. Results: A total of 112 eyes from 56 patients with an average age of 72.6 ± 6.9 years were enrolled. At baseline, significantly higher CC FD% and thinner CC thickness were observed on the surgical side (eyes ipsilateral to the side of CEA) versus the nonsurgical side (eyes contralateral to the side of CEA) (P = 0.001 and P = 0.03, respectively). Following CEA, a significant reduction in CC FD% and a significant increase in CC thickness were detected on the surgical as compared with the nonsurgical side (P = 0.008 and P = 0.01, respectively). Smoking status positively affected CC FD% change (coefficient of variation [CV] = 0.84, P = 0.01) on the surgical side and negatively affected CC thickness change on both the surgical side (CV = -0.382, P = 0.009) and the nonsurgical side (CV = -0.321, P = 0.04). The degree of stenosis demonstrated a positive influence on CC FD% change (CV = 0.040, P = 0.02) on the surgical side. Conclusions: Unilateral CEA on the side of clinically significant CAS increases carotid blood flow, which further results in improved CC perfusion.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Humanos , Anciano , Perfusión , Coroides , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Algoritmos
14.
Cell Rep ; 42(11): 113371, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37938972

RESUMEN

Senescent cells are a major contributor to age-dependent cardiovascular tissue dysfunction, but knowledge of their in vivo cell markers and tissue context is lacking. To reveal tissue-relevant senescence biology, we integrate the transcriptomes of 10 experimental senescence cell models with a 224 multi-tissue gene co-expression network based on RNA-seq data of seven tissues biopsies from ∼600 coronary artery disease (CAD) patients. We identify 56 senescence-associated modules, many enriched in CAD GWAS genes and correlated with cardiometabolic traits-which supports universality of senescence gene programs across tissues and in CAD. Cross-tissue network analyses reveal 86 candidate senescence-associated secretory phenotype (SASP) factors, including COL6A3. Experimental knockdown of COL6A3 induces transcriptional changes that overlap the majority of the experimental senescence models, with cell-cycle arrest linked to modulation of DREAM complex-targeted genes. We provide a transcriptomic resource for cellular senescence and identify candidate biomarkers, SASP factors, and potential drivers of senescence in human tissues.


Asunto(s)
Senescencia Celular , Transcriptoma , Humanos , Transcriptoma/genética , Senescencia Celular/genética , Fenotipo , Biomarcadores , Colágeno , Colágeno Tipo VI/genética
15.
Viruses ; 15(11)2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38005849

RESUMEN

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel "block-lock-stop" approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.


Asunto(s)
Retrovirus Endógenos , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Latencia del Virus , Provirus/genética , Seropositividad para VIH/genética , Linfocitos T CD4-Positivos
16.
Orthop J Sports Med ; 11(9): 23259671231187442, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37786478

RESUMEN

Background: Anterior cruciate ligament (ACL) reconstruction (ACLR) is associated with postoperative pain and necessitates using perioperative nerve blocks and multimodal analgesic plans. Purpose: To assess postoperative pain and daily opioid use after ACL repair versus ACLR and to assess whether ACL repair could be performed successfully without using long-acting nerve blocks. Study Design: Cohort study; Level of evidence, 2. Methods: All eligible patients who underwent ACL surgery between 2019 and 2022 were prospectively enrolled. Patients were treated with primary repair if proximal tears with sufficient tissue quality were present; otherwise, they underwent single-bundle ACLR with either hamstring tendon or quadriceps tendon autograft. The patients were divided into 3 groups: ACLR with adductor canal nerve block (up to 20 mL of 0.25% bupivacaine with 2 mg dexamethasone), primary repair with nerve block, and primary repair without nerve block. Pain visual analog scale and number of opioids used were recorded during the first 14 postoperative days (PODs). Furthermore, patients completed the Quality of Recovery-15 (QoR-15) survey, and range of motion was assessed. Group differences were compared using Mann-Whitney U test and chi-square test. Results: Seventy-eight patients were included: 30 (39%) underwent ACLR, 19 (24%) ACL repair with nerve block, and 29 (37%) ACL repair without nerve block. Overall, the ACL repair group used significantly fewer opioids than the ACLR group on POD 1 (1 vs 3, P = .027) and POD 2 (1 vs 3, P = .014) while also using fewer opioids in total (3 vs 8, P = .038). This difference was even more marked when only analyzing those patients who received postoperative nerve blocks (1 vs 8, P = .029). Repair patients had significantly higher QoR-15 scores throughout the first postoperative week, and they had greater range of motion (all P < .05). There were no significant differences in pain scores, opioid usage, or QoR-15 scores between patients who underwent repair with versus without nerve block. Conclusion: The ACL repair group experienced less postoperative pain during the first 2 weeks after surgery and used significantly fewer opioids than the ACLR group. Furthermore, they had improved knee function and higher recovery quality than patients who underwent ACLR during the initial postoperative period. Postoperative nerve blocks may not be necessary after ACL repair.

17.
Arthrosc Sports Med Rehabil ; 5(6): 100799, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37822672

RESUMEN

Purpose: To assess the clinical and patient-reported outcome measures (PROMs) of acute superficial medial collateral ligament (sMCL) repair with suture augmentation (SA) in the setting of a multiligamentous injured knees (MLIKs) at 2-year follow-up. Methods: A retrospective analysis of consecutive patients with MLIK with grade III sMCL injuries who underwent acute (<6 weeks) sMCL repair with SA was conducted. Clinical follow-up was performed at minimum 1-year postoperatively, and PROMs were collected at the latest follow-up (minimum 2 years' postoperatively). Continuous variables were reported in median with interquartile range (IQR). Results: A total of 20 patients (41.4 [28.5-47.9] years of age) with grade III sMCL injury and additional injury to 1 cruciate ligament (KDI-M; n = 13) or bicruciate (KDIII-M; n = 7) were enrolled with a median follow-up of 4.3 (3.6-5.2) years. In total, 90% (n = 18) of patients with MLIK treated with acute sMCL repair and early range of motion rehabilitation protocol demonstrated negative valgus laxity stress testing in 0 and 30° flexion and low reoperation rates (n = 1, 5%) due to stiffness. In addition, good-to-excellent subjective outcomes were reported at final follow-up: median International Knee Documentation Committee 82.2 (78.7-90.8), Lysholm 95.0 (90.0-100.0), modified Cincinnati Score 89.0 (83.3-96.0), Single Assessment Numeric Evaluation 90.0 (83.8-95.0), Forgotten Joint Score 79.2 (62.5-91.7), Tegner 5.0 (IQR 4.0-6.0), and ACL-Return to Sport after Injury Scale 78.3 (IQR 66.7-90.0). Conclusions: In this study, 20 heterogenous patients with MLIKs treated with acute percutaneous sMCL repair with SA had excellent stability, low rates of postoperative stiffness, and good-to-excellent PROMs at short-term follow-up. Level of Evidence: Level IV, therapeutic case series.

18.
Invest Ophthalmol Vis Sci ; 64(13): 16, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37819744

RESUMEN

Purpose: Choroidal changes before and after anti-VEGF therapy were investigated in eyes with exudative AMD to determine if there was a difference between eyes with macular neovascularization (MNV) that arises from the choroid (type 1 or 2) versus the retinal circulation (type 3). Methods: Patients with treatment-naïve AMD were imaged with swept-source optical coherence tomography angiography using a 12 × 12-mm scan pattern. The mean choroidal thickness and choroidal vascularity index (CVI) were measured within 5-mm and 11-mm fovea-centered circles before, at the onset of, and after anti-VEGF therapy. Results: Forty-one eyes of 37 patients were included; 24 eyes with type 1 MNV, 4 eyes with type 2 MNV, and 13 eyes with type 3 MNV. Within the 5-mm and 11-mm circles, the mean choroidal thickness and CVI measurements increased from pretreatment to the onset of exudation (P ≤ 0.03). The mean choroidal thickness and CVI measurements decreased from the onset of exudation to after treatment (P < 0.001). No significant changes in mean choroidal thickness or CVI were observed when comparing measurements before or after treatment (P ≥ 0.38). No significant differences in mean choroidal thickness or CVI measurements were observed between eyes with type 1 or 2 MNV and type 3 MNV. Conclusions: In treatment-naïve AMD eyes with MNV, the choroidal thickness and vascularity increased at the onset of exudation and then decreased after anti-VEGF therapy. This finding suggests that these choroidal changes develop in response to the proangiogenic milieu before treatment and in response to treatment, regardless of the site of origin for the MNV.


Asunto(s)
Neovascularización Coroidal , Tomografía de Coherencia Óptica , Humanos , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Coroides , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/tratamiento farmacológico , Retina
19.
Plast Reconstr Surg Glob Open ; 11(10): e5355, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37850204

RESUMEN

Background: Breast-conserving therapy with oncoplastic reduction is a useful strategy for partial mastectomy defect reconstruction. The most recently published systematic review of oncoplastic breast reduction outcomes from 2015 showed wound dehiscence in 4.3%, hematoma in 0.9%, infection in 2.8%, and nipple necrosis in 0.9% of patients. We performed a systematic review of oncoplastic breast reduction literature, comparing outcomes and complication rates reported over the past 8 years. Methods: Studies describing the use of oncoplastic breast reduction and discussion of postoperative complications were included. The primary outcome assessed was the postoperative complication rate; secondary outcomes analyzed were rates of margin expansion, completion mastectomy, and delays in adjuvant therapy due to complications. Results: Nine articles met inclusion criteria, resulting in 1715 oncoplastic breast reduction patients. The mean rate of hematoma was 3%, nipple necrosis was 2%, dehiscence was 4%, infection was 3%, and seroma was 2%. The need for re-excision of margins occurred in 8% of patients, and completion mastectomy in 2%. Finally, delay in adjuvant treatment due to a postoperative complication occurred in 4% of patients. Conclusions: Oncoplastic breast reduction is an excellent option for many patients undergoing breast-conserving therapy; however, postoperative complications can delay adjuvant radiation therapy. Results of this systematic literature review over the past 8 years showed a slight increase in complication rate compared to the most recent systematic review from 2015. With increased popularity and surgeon familiarity, oncoplastic breast reduction remains a viable option for reconstruction of partial mastectomy defects despite a slight increase in complication rate.

20.
Biomedicines ; 11(10)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37892982

RESUMEN

CD4+ T cells have orchestrated and regulated immunity since the introduction of jawed vertebrates, yet our understanding of CD4+ T cell evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and high-resolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi-omics data that can be used as a reference atlas and index to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.

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