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1.
Eur Spine J ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965087

RESUMO

INTRODUCTION: Degenerative spondylolisthesis causes translational and angular malalignment, resulting in a loss of segmental lordosis. This leads to compensatory adjustments in adjacent levels to maintain balance. Lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF) are common techniques at L4-5. This study compares compensatory changes at adjacent L3-4 and L5-S1 levels six months post LLIF versus TLIF for grade 1 degenerative spondylolisthesis at L4-5. METHODS: A retrospective study included patients undergoing L4-5 LLIF or TLIF with posterior pedicle screw instrumentation (no posterior osteotomy) for grade 1 spondylolisthesis. Pre-op and 6-month post-op radiographs measured segmental lordosis (L3-L4, L4-L5, L5-S1), lumbar lordosis (LL), and pelvic incidence (PI), along with PI-LL mismatch. Multiple regressions were used for hypothesis testing. RESULTS: 113 patients (61 LLIF, 52 TLIF) were studied. TLIF showed less change in L4-5 lordosis (mean = 1.04°, SD = 4.34) compared to LLIF (mean = 4.99°, SD = 5.53) (p = 0.003). L4-5 angle changes didn't correlate with L3-4 changes, and no disparity between LLIF and TLIF was found (all p > 0.16). In LLIF, greater L4-5 lordosis change predicted reduced compensatory L5-S1 lordosis (p = 0.04), while no significant relationship was observed in TLIF patients (p = 0.12). CONCLUSION: LLIF at L4-5 increases lordosis at the operated level, with compensatory decrease at L5-S1 but not L3-4. This reciprocal loss at adjacent L5-S1 may explain inconsistent improvement in lumbar lordosis (PI-LL) post L4-5 fusion.

2.
Int J Mol Sci ; 24(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37047796

RESUMO

Gene expression profiling (GEP) is clinically validated to stratify the risk of metastasis by assigning uveal melanoma (UM) patients to two highly prognostic molecular classes: class 1 (low metastatic risk) and class 2 (high metastatic risk). However, GEP requires intraocular tumor biopsy, which is limited by small tumor size and tumor heterogeneity; furthermore, there are small risks of retinal hemorrhage, bleeding, or tumor dissemination. Thus, ocular liquid biopsy has emerged as a less-invasive alternative. In this study, we seek to determine the aqueous humor (AH) proteome related to the advanced GEP class 2 using diagnostic AH liquid biopsy specimens. Twenty AH samples were collected from patients with UM, grouped by GEP classes. Protein expression levels of 1472 targets were analyzed, compared between GEP classes, and correlated with clinical features. Significant differentially expressed proteins (DEPs) were subjected to analysis for cellular pathway and upstream regulator identification. The results showed that 45 DEPs detected in the AH could differentiate GEP class 1 and 2 at diagnosis. IL1R and SPRY2 are potential upstream regulators for the 8/45 DEPs that contribute to metastasis-related pathways. AH liquid biopsy offers a new opportunity to determine metastatic potential for patients in the absence of tumor biopsy.


Assuntos
Proteoma , Neoplasias Uveais , Humanos , Humor Aquoso/metabolismo , Neoplasias Uveais/genética , Biópsia por Agulha Fina , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização Intracelular
3.
World J Surg ; 46(12): 3043-3050, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36167834

RESUMO

INTRODUCTION: We performed Thyroseq v2 molecular testing on indeterminate thyroid nodules and evaluated whether they underwent a management change from the standard of thyroid lobectomy. METHODS: We conducted a retrospective analysis of all indeterminate thyroid nodules that underwent Thyroseq v2 molecular testing from 2014 to 2019 at a large academic center. Pathology was reviewed by thyroid cytopathologists. Thyroseq results were reported benign (malignancy probability less than 10%) or suspicious (malignancy probability greater than 30%). The primary endpoint was a management change from a diagnostic lobectomy. RESULTS: A total of 142 nodules were included: 113 (80%) Bethesda III and 29 (20%) Bethesda IV. Seventy-three nodules underwent surgical management and 69 did not. We noted a change in management in 64% (91/142) of nodules. Patients who underwent a change in management to no surgery had a significantly higher rate of benign Thyroseq result than those without a change (75.8% vs. 49.0%, p = 0.001). On logistic regression analysis, a benign Thyroseq result was a positive independent predictor of a change to no surgery (OR 3.87, 95% CI 1.69-8.89). Nodule size, multiple nodules, compressive symptoms, and history of hypothyroidism were not significant. Of the 91 patients who underwent a management change, 71% (65/91) did not undergo surgery. On follow-up (average 985 ± 615 days), 12% (8/65) of those nodules were growing or developed suspicious features requiring surgery. CONCLUSIONS: Molecular testing helped avoid surgery in almost half our population with indeterminate thyroid nodules, and benign results may help avoid surgery in asymptomatic patients with indeterminate thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Técnicas de Diagnóstico Molecular , Tomada de Decisões , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia
4.
J Artif Organs ; 25(1): 16-23, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33982206

RESUMO

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes.Field of research: Artificial lung/ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/cirurgia , Humanos , Sistema de Registros , Estudos Retrospectivos , Choque Cardiogênico/cirurgia , Resultado do Tratamento
5.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682905

RESUMO

Tumor biopsy can identify prognostic biomarkers for metastatic uveal melanoma (UM), however aqueous humor (AH) liquid biopsy may serve as an adjunct. This study investigated whether the AH of UM eyes has sufficient circulating tumor DNA (ctDNA) to perform genetic analysis. This is a case series of 37 AH samples, taken before or after radiation, and one tumor wash sample, from 12 choroidal and 8 ciliary body (CB) melanoma eyes. AH was analyzed for nucleic acid concentrations. AH DNA and one tumor wash sample underwent shallow whole-genome sequencing followed by Illumina sequencing to detect somatic copy number alterations (SCNAs). Four post-radiation AH underwent targeted sequencing of BAP1 and GNAQ genes. Post-radiation AH had significantly higher DNA and miRNA concentrations than paired pre-radiation samples. Highly recurrent UM SCNAs were identified in 0/11 post-radiation choroidal and 6/8 post-radiation CB AH. SCNAs were highly concordant in a CB post-radiation AH with its matched tumor (r = 0.978). BAP1 or GNAQ variants were detected in 3/4 post-radiation AH samples. AH is a source of ctDNA in UM eyes, particularly in post-radiation CB eyes. For the first time, UM SCNAs and mutations were identified in AH-derived ctDNA. Suggesting that AH can serve as a liquid biopsy for UM.


Assuntos
Melanoma , Neoplasias Uveais , Humor Aquoso , Humanos , Biópsia Líquida , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Mutação , Recidiva Local de Neoplasia , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/genética , Neoplasias Uveais/patologia
6.
Nutr Neurosci ; 22(10): 738-743, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29433376

RESUMO

Objectives: We tested whether supplementing with pomegranate polyphenols can enhance cognitive/functional recovery after stroke. Methods: In this parallel, block-randomized clinical trial, we administered commercially-available pomegranate polyphenol or placebo pills twice per day for one week to adult inpatients in a comprehensive rehabilitation setting starting approximately 2 weeks after stroke. Pills contained 1 g of polyphenols derived from whole pomegranate, equivalent to levels in approximately 8 oz of juice. Placebo pills were similar to the pomegranate pills except that they contained only lactose. Of the 163 patients that were screened, 22 were eligible and 16 were randomized (8 per group). We excluded one subject per group from the neuropsychological analyses since they were lost to follow-up, but we included all subjects in the analysis of functional data since outcome data were available. Clinicians and subjects were blinded to group assignment. Neuropsychological testing (primary outcome: Repeatable Battery for the Assessment of Neuropsychological Status) and functional independence scores were used to determine changes in cognitive and functional ability. Results: Pomegranate-treated subjects demonstrated more neuropsychological and functional improvement and spent less time in the hospital than placebo controls. Discussion: Pomegranate polyphenols enhanced cognitive and functional recovery after stroke, justifying pursuing larger clinical trials.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Cognição/efeitos dos fármacos , Polifenóis/administração & dosagem , Punica granatum , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
7.
Cardiol Young ; 29(11): 1391-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31554530

RESUMO

BACKGROUND: The resection of a subaortic membrane remains far from a curative operation. We sought to examine factors associated with reoperation and the degree of aortic valve regurgitation as a potential long-term source for reoperation. METHODS: All patients who underwent resection of an isolated subaortic membrane between 1995 and 2018 were included. Patients who underwent other procedures were excluded. Paired categorical data were compared using McNemar's test. Univariate time-to-event analyses were performed using Kaplan-Meier methods with log-rank tests for categorical variables and univariate Cox models for continuous variables. RESULTS: A total of 84 patients (median age 6.6, 31% females) underwent resection of isolated subaortic membrane. At a median follow-up of 9.3 years (interquartile range 0.6-22.5), 12 (14%) patients required one reoperation and 1 patient required two reoperations. Median time to first reoperation was 4.6 years. The degree of aortic valve regurgitation improved post-operatively from pre-operatively (p = 0.0007); however, the degree of aortic valve regurgitation worsened over the course of follow-up (p = 0.010) to equivalence with pre-operative aortic valve regurgitation (p = 0.18). Performance of a septal myectomy was associated with longer freedom from reoperation (p = 0.004). CONCLUSIONS: In patients with isolated subaortic membranes, performance of a septal myectomy can minimise risk for reoperation. Patients should be serially monitored for degradation of the aortic valve, even if aortic regurgitation is not present post-operatively.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Estenose Subaórtica Fixa/cirurgia , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Criança , Pré-Escolar , Estenose Subaórtica Fixa/diagnóstico , Ecocardiografia , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
8.
Biophys J ; 112(7): 1431-1443, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28402885

RESUMO

To better understand animal cell plasma membranes, we studied simplified models, namely four-component lipid bilayer mixtures. Here we describe the domain size transition in the region of coexisting liquid-disordered (Ld) + liquid-ordered (Lo) phases. This transition occurs abruptly in composition space with domains increasing in size by two orders of magnitude, from tens of nanometers to microns. We measured the line tension between coexisting Ld and Lo domains close to the domain size transition for a variety of lipid mixtures, finding that in every case the transition occurs at a line tension of ∼0.3 pN. A computational model incorporating line tension and dipole repulsion indicated that even small changes in line tension can result in domains growing in size by several orders of magnitude, consistent with experimental observations. We find that other properties of the coexisting Ld and Lo phases do not change significantly in the vicinity of the abrupt domain size transition.


Assuntos
Fenômenos Biofísicos , Bicamadas Lipídicas/química , Transição de Fase , Espectroscopia de Ressonância de Spin Eletrônica , Simulação de Dinâmica Molecular , Difração de Nêutrons , Espalhamento a Baixo Ângulo
9.
JACC Adv ; 3(5): 100916, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38939630

RESUMO

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known. Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation. Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m2 and systemic vascular resistance <800 dyne/s/cm5, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed. Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index. Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.

10.
J Am Chem Soc ; 135(10): 3796-9, 2013 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23448269

RESUMO

The ruthenium(0) catalyst generated from Ru3(CO)12 and tricyclohexylphosphine or BIPHEP promotes successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons across the diol, hydroxyketone, and dione oxidation levels to form products of [4 + 2] cycloaddition. A mechanism involving diene-carbonyl oxidative coupling followed by intramolecular carbonyl addition from the resulting allylruthenium intermediate is postulated.


Assuntos
Álcoois/química , Aldeídos/química , Alcadienos/química , Hidrocarbonetos Aromáticos/síntese química , Cetonas/química , Rutênio/química , Catálise , Ciclização , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Oxirredução
11.
Nat Genet ; 36(2): 138-45, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14716315

RESUMO

Centromeres are the last frontiers of complex eukaryotic genomes, consisting of highly repetitive sequences that resist mapping, cloning and sequencing. The centromere of rice Chromosome 8 (Cen8) has an unusually low abundance of highly repetitive satellite DNA, which allowed us to determine its sequence. A region of approximately 750 kb in Cen8 binds rice CENH3, the centromere-specific H3 histone. CENH3 binding is contained within a larger region that has abundant dimethylation of histone H3 at Lys9 (H3-Lys9), consistent with Cen8 being embedded in heterochromatin. Fourteen predicted and at least four active genes are interspersed in Cen8, along with CENH3 binding sites. The retrotransposons located in and outside of the CENH3 binding domain have similar ages and structural dynamics. These results suggest that Cen8 may represent an intermediate stage in the evolution of centromeres from genic regions, as in human neocentromeres, to fully mature centromeres that accumulate megabases of homogeneous satellite arrays.


Assuntos
Centrômero/genética , Oryza/genética , Cromossomos Artificiais Bacterianos , DNA Satélite , Genes , Dados de Sequência Molecular , Fases de Leitura Aberta , Retroelementos
12.
J La State Med Soc ; 165(1): 26-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23550394

RESUMO

An anaplastic large cell lymphoma (ALCL) arising from the breast tissue is an extremely rare cancer possibly associated with breast implants. According to the FDA database, there are only approximately 60 reported cases of ALCLs in women with breast implants worldwide, and there is the possibility that some of those are duplicate reports of a single case. Here, we present a case of ALCL in a woman who had breast implants for more than 10 years. We discuss preoperative imaging and intraoperative findings, along with the histopathology features and the postoperative management. We suggest that the possibility of late presentation of ALCL be discussed with the patients when we offer and consent them for implant reconstructions following breast surgeries. Increased awareness of the patients and the physicians would make the diagnosis of this entity less of a challenge.


Assuntos
Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Adulto , Neoplasias da Mama/diagnóstico por imagem , Feminino , Educação em Saúde , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ultrassonografia
13.
J Voice ; 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36038478

RESUMO

OBJECTIVES: The COVID-19 pandemic expanded the use of telemedicine, but there is no literature exploring both patient and provider satisfaction specifically in the provision of voice therapy. This study aims to investigate patient and provider satisfaction with virtual voice therapy, its associated factors, and any correlation between the two. METHODS: Cross-sectional study. Participants included 226 adults who underwent voice therapy delivered via telepractice at the USC Voice Center between April and October 2020. Patients and providers self-reported their level of satisfaction on a visual analog scale (VAS; range 0-100). Patient satisfaction was additionally measured using a previously validated Telemedicine Satisfaction Questionnaire (TSQ; range 1-5), and a binary question about their desire to choose telemedicine over in-person therapy in the future. Three speech-language pathologists rated provider satisfaction for all 226 patients. Patient satisfaction survey was completed by 55 patients. Multivariable linear regression analyses and linear mixed-effects models were used to assess the results. RESULTS: Patient and provider mean (SD) VAS satisfaction scores were 86.8 (18.6) and 80.6 (19.7), respectively. The mean (SD) TSQ score was 4.4 (0.6). In a multivariable model, patient satisfaction levels were significantly higher for hypofunctional than for hyperfunctional dysphonia diagnoses. Forty-four (73%) patients reported they would prefer telemedicine voice therapy over in-person appointments, which was significantly correlated with internet reliability (P = 0.04). For providers, satisfaction was significantly lower for patients whose diagnosis had changed after initiation of voice therapy (Δ = -16.0 [95% CI: -28.7 to -3.2]) and for encounters with Asian patients compared to White patients (Δ = -11.6 [95% CI: -18.9 to -4.2]). Patient and provider satisfaction scores were weakly correlated (r = 0.19). CONCLUSIONS: Our findings suggest that virtual voice therapy is not simply an alternative to in-person service, but rather an effective method useful beyond the current pandemic with proper diagnosis and technical support.

14.
Sci Rep ; 12(1): 11416, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794145

RESUMO

Direct cell reprogramming represents a promising new myocardial regeneration strategy involving in situ transdifferentiation of cardiac fibroblasts into induced cardiomyocytes. Adult human cells are relatively resistant to reprogramming, however, likely because of epigenetic restraints on reprogramming gene activation. We hypothesized that modulation of the epigenetic regulator gene p63 could improve the efficiency of human cell cardio-differentiation. qRT-PCR analysis demonstrated significantly increased expression of a panel of cardiomyocyte marker genes in neonatal rat and adult rat and human cardiac fibroblasts treated with p63 shRNA (shp63) and the cardio-differentiation factors Hand2/Myocardin (H/M) versus treatment with Gata4, Mef2c and Tbx5 (GMT) with or without shp63 (p < 0.001). FACS analysis demonstrated that shp63+ H/M treatment of human cardiac fibroblasts significantly increased the percentage of cells expressing the cardiomyocyte marker cTnT compared to GMT treatment with or without shp63 (14.8% ± 1.4% versus 4.3% ± 1.1% and 3.1% ± 0.98%, respectively; p < 0.001). We further demonstrated that overexpression of the p63-transactivation inhibitory domain (TID) interferes with the physical interaction of p63 with the epigenetic regulator HDAC1 and that human cardiac fibroblasts treated with p63-TID+ H/M demonstrate increased cardiomyocyte marker gene expression compared to cells treated with shp63+ H/M (p < 0.05). Whereas human cardiac fibroblasts treated with GMT alone failed to contract in co-culture experiments, human cardiac fibroblasts treated with shp63+ HM or p63-TID+ H/M demonstrated calcium transients upon electrical stimulation and contractility synchronous with surrounding neonatal cardiomyocytes. These findings demonstrate that p63 silencing provides enhanced rat and human cardiac fibroblast transdifferentiation into induced cardiomyocytes compared to a standard reprogramming strategy. p63-TID overexpression may be a useful reprogramming strategy for overcoming epigenetic barriers to human fibroblast cardio-differentiation.


Assuntos
Miócitos Cardíacos , Proteínas com Domínio T , Animais , Reprogramação Celular , Epigênese Genética , Fibroblastos/metabolismo , Humanos , Proteínas de Membrana/genética , Miócitos Cardíacos/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ratos , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Neuron ; 56(4): 621-39, 2007 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-18031681

RESUMO

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.


Assuntos
Córtex Cerebral/anormalidades , Córtex Cerebral/citologia , Dendritos/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas do Tecido Nervoso/genética , Células Piramidais/citologia , Animais , Diferenciação Celular/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Dendritos/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Proteína 4 Homóloga a Disks-Large , Potenciais Pós-Sinápticos Excitadores/genética , Feminino , Guanilato Quinases , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Vias Neurais/anormalidades , Vias Neurais/citologia , Vias Neurais/metabolismo , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Células Piramidais/metabolismo , Transmissão Sináptica/genética
16.
Int J Med Stud ; 9(1): 37-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35782466

RESUMO

Background: The cost of eyeglasses is variably covered by medical insurance and thus is a significant barrier for patients in lower socioeconomic classes. We evaluated the efficacy of Recycle Vision (RV) at LAC+USC Medical Center, a monthly clinic run by volunteer medical students that provides free donated eyeglasses. Methods: A convenience sample of 30 patients was surveyed from August 1, 2019 to December 31, 2019. Patients' prescriptions were matched with available eyeglasses based on spherical equivalent and axis of astigmatism using Winglasses software algorithm; patients selected glasses from these options based on subjective improvement of vision. All participants consented to a phone follow-up survey 1 month after initial visit to gauge satisfaction with glasses and rate difficulty in completing daily activities pre- and post-RV visit on a scale of 1 to 5 (5 being the greatest), with a 100% response rate. Results: Of the 30 study participants, 90% received eyeglasses from RV, with reported improvement in ease of daily activities of 3.96. 67% of respondents stated that if RV clinic did not exist, they would not have obtained glasses elsewhere; cost was the most commonly (70%) cited barrier. Upon follow-up, average likelihood of patients referring friends/family to RV was 4.07 (SD 1.14). Conclusion: The majority of RV patients received free eyeglasses and had subsequent improvement in their quality of life. This pilot study demonstrates that programs offering free eyeglasses can effectively correct refractive error and can offer a practical public health solution to improve functionality for underserved populations.

17.
Cells ; 10(8)2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34440893

RESUMO

The heartbeat is initiated by pacemaker cells residing in the sinoatrial node (SAN). SAN cells generate spontaneous action potentials (APs), i.e., normal automaticity. The sympathetic nervous system increases the heart rate commensurate with the cardiac output demand via stimulation of SAN ß-adrenergic receptors (ßAR). While SAN cells reportedly represent a highly heterogeneous cell population, the current dogma is that, in response to ßAR stimulation, all cells increase their spontaneous AP firing rate in a similar fashion. The aim of the present study was to investigate the cell-to-cell variability in the responses of a large population of SAN cells. We measured the ßAR responses among 166 single SAN cells isolated from 33 guinea pig hearts. In contrast to the current dogma, the SAN cell responses to ßAR stimulation substantially varied. In each cell, changes in the AP cycle length were highly correlated (R2 = 0.97) with the AP cycle length before ßAR stimulation. While, as expected, on average, the cells increased their pacemaker rate, greater responses were observed in cells with slower basal rates, and vice versa: cells with higher basal rates showed smaller responses, no responses, or even decreased their rate. Thus, ßAR stimulation synchronized the operation of the SAN cell population toward a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of ßAR-driven fight-or-flight responses among individual pacemaker cells.


Assuntos
Potenciais de Ação/fisiologia , Animais , Cobaias , Frequência Cardíaca/fisiologia , Miócitos Cardíacos/fisiologia , Nó Sinoatrial/metabolismo , Nó Sinoatrial/fisiologia
18.
J Vis Exp ; (175)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34570090

RESUMO

There is significant potential clinical utility for the application of a liquid biopsy platform for retinoblastoma, given that direct tumor biopsy is prohibited in these patients. The aqueous humor (AH) forms in a separate compartment from the tumor but is enclosed within the same ocular space. Thus, it is an enriched source of eye-specific tumoral genomic information that can be used as a liquid biopsy or surrogate to tumor biopsy for this disease. This manuscript details a methodology for safely extracting the AH from retinoblastoma eyes via clear corneal paracentesis. Additionally, the steps for genomic analysis, including cell-free DNA isolation and purification, next-generation sequencing, somatic copy number alteration (SCNA) analysis, RB1 single nucleotide variant (SNV) mutation identification, and tumor fraction estimation are presented. The pre-analytical, analytical, and early clinical validity of the AH liquid biopsy platform have been evaluated; however, it is not without limitations. These are largely a consequence of the quantity of cell-free DNA that is required for certain steps of the assay. Compared to other blood-based liquid biopsy platforms currently under investigation for retinoblastoma, an AH-based platform is limited by the volume of biofluid (and thus the quantity of DNA) that can be extracted from the eye; the benefit is that AH is eye-specific. The platform discussed here is unique in that it detects circulating tumor DNA in the AH via two mechanisms (SCNAs and RB1 SNVs), yielding a higher sensitivity for identifying tumoral genomic information. The AH liquid biopsy has the potential for direct clinical application to precision oncology for retinoblastoma patients, with particular importance for patients with bilateral disease as the AH is specific to the tumors in each eye. There is ongoing research with applications of this platform to patients with other ocular tumors as well.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humor Aquoso , Genômica , Humanos , Biópsia Líquida , Paracentese , Medicina de Precisão , Neoplasias da Retina/genética , Retinoblastoma/genética
19.
OTO Open ; 5(4): 2473974X211059081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805720

RESUMO

OBJECTIVE: In patients with a history of lymphoma who demonstrate palatine tonsil uptake on posttreatment PET/CT (positron emission tomography/computed tomography), tonsillectomy is often performed to evaluate for lymphoma recurrence. However, predictive clinical and imaging factors for true tonsil recurrence in this setting are not well established; this will be explored herein. STUDY DESIGN: Retrospective case series. SETTING: Patients treated at a tertiary medical center from January 2008 to May 2020. METHODS: Chart review was performed on all patients with a history of treated lymphoma in clinical remission who presented for evaluation of abnormal PET/CT imaging findings and subsequently underwent tonsillectomy. RESULTS: Among 15 patients who met inclusion criteria, 14 had benign findings on surgical pathology, yielding a false-positive rate of 93%. The patient with malignancy was identified on biopsy after inconclusive surgical pathology and is the only documented case of recurrence in this specific patient population throughout the literature. The patient presented with B symptoms, irregularly shaped tonsils, increased lymph node activity on PET/CT, and uptrending bilateral tonsil activity but with one of the lowest maximum standardized uptake values of the cohort. The singular distinguishing feature for the patient with recurrent disease was a prior tonsil biopsy suspicious for recurrence, which prompted the otolaryngology referral. CONCLUSION: PET/CT lacks specificity in identifying lymphoma recurrence in the oropharynx. Clinical and radiographic features that were previously considered concerning for recurrence are most likely not indicative of malignancy in this patient population. Our findings call into question whether tonsillectomy should be routinely performed in this patient population.

20.
Adv Radiat Oncol ; 6(5): 100737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307966

RESUMO

PURPOSE: Ocular brachytherapy is a standard-of-care surgical procedure for globe salvage in the treatment of uveal melanoma. The procedure involves the placement and subsequent removal of a radioactive plaque several days later. At many locations, patients are admitted on an inpatient basis until plaque removal due to radiation safety concerns. However, patients may be discharged to home after plaque insertion, and subsequently return to the medical facility for plaque removal. This study aimed to evaluate the safety and systematic financial benefit of the outpatient ocular brachytherapy program at "?>the University of Southern California (USC) Roski Eye Institute for 30 years. METHODS AND MATERIALS: A single-institution retrospective record review was performed on all 275 patients who underwent brachytherapy for ocular tumors between January 1, 1989 and December 31, 2019 to assess for occurrences of reportable radiation and/or patients safety events. The treatment protocols at our institution are described. Data on hospital-adjusted expenses per inpatient day from the American Hospital Association's 2018 Annual Survey were used as a proxy for costs to patients and the health care system to perform a cost-benefit analysis comparing outpatient versus inpatient brachytherapy. RESULTS: Of the 275 plaque procedures over a 30-year period that were reviewed, there were no internally or externally reportable patient or radiation safety events. There were no adverse events related to patient transportation to the hospital, the patient not returning for plaque removal, operative issues in removing the plaque on time due to cancelled or delayed cases, or loss of radioactive material. Additionally, our cost-benefit analysis estimates that outpatient brachytherapy reduced costs for USC's patients in 2018 by an average of $24,722 per patient treated with ocular brachytherapy. CONCLUSIONS: With appropriate measures, outpatient ocular brachytherapy allows patients to safely return home with the added benefit of decreased financial burden for both patients and the broader health care system.

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