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1.
Front Public Health ; 10: 852083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493369

RESUMO

Polymerase chain reaction (PCR) remains the gold standard in disease diagnostics due to its extreme sensitivity and specificity. However, PCR tests are expensive and complex, require skilled personnel and specialized equipment to conduct the tests, and have long turnaround times. On the other hand, lateral flow immunoassay-based antigen tests are rapid, relatively inexpensive, and can be performed by untrained personnel at the point of care or even in the home. However, rapid antigen tests are less sensitive than PCR since they lack the inherent target amplification of PCR. It has been argued that rapid antigen tests are better indicators of infection in public health decision-making processes to test, trace, and isolate infected people to curtail further transmission. Hence, there is a critical need to increase the sensitivity of rapid antigen tests and create innovative solutions to achieve that goal. Herein, we report the development of a low-cost diagnostic platform, enabling rapid detection of SARS-CoV-2 under field or at-home conditions. This platform (Halo™) is a small, highly accurate, consumer-friendly diagnostic reader paired with fluorescently labeled lateral flow assays and custom software for collection and reporting of results. The focus of this study is to compare the analytical performance of HaloTM against comparable tests that use either colloidal gold nanoparticles or fluorescence-based reporters in simulated nasal matrix and not in clinical samples. Live virus data has demonstrated limit of detection performance of 1.9 TCID50/test in simulated nasal matrix for the delta variant, suggesting that single-assay detection of asymptomatic SARS-CoV-2 infections may be feasible. Performance of the system against all tested SARS CoV-2 virus variants showed comparable sensitivities indicating mutations in SARS-CoV-2 variants do not negatively impact the assay.


Assuntos
COVID-19 , Nanopartículas Metálicas , COVID-19/diagnóstico , Ouro , Humanos , Estudo de Prova de Conceito , SARS-CoV-2
2.
Mod Pathol ; 24(2): 288-96, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21057460

RESUMO

LIN28 has been shown to have an important role in primordial germ cell development and malignant transformation of germ cells in mouse. In this study, we examined the immunohistochemical profile of LIN28 in 131 primary human extragonadal germ cell tumors (central nervous system (CNS) 76, mediastinum 17, sacrococcygeal region 30, pelvis 3, vagina 2, liver 1, omentum 1, and retroperitoneum 1), including the following tumors and/or components: 57 seminomas/germinomas, 10 embryonal carcinomas, 74 yolk sac tumors, 6 choriocarcinomas, 15 mature, and 13 immature teratomas. We compared LIN28 with SALL4 to assess its diagnostic value. To determine its specificity, we examined LIN28 in 406 extragonadal-non-germ cell tumors (103 carcinomas, 91 sarcomas, 9 melanomas, 12 mesotheliomas, 83 lymphomas, 9 plasmacytomas, 82 CNS tumors, and 17 thymic epithelial tumors). The staining was semi-quantitatively scored as 0 (no cell stained), 1+ (0-30%), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). LIN28 staining was seen in all seminomas/germinomas (3+ in 1 and 4+ in 56), embryonal carcinomas (4+ in all 10), and yolk sac tumors (3+ in 3 and 4+ in 71). Variable LIN28 staining was seen in 5 of 6 choriocarcinomas (1+ to 4+), 8 of 13 immature teratomas (1+ to 2+ in immature elements), and in 1 of 15 mature teratomas (1+). Only 11 of 406 non-germ cell tumors showed 1+ LIN28 staining. Therefore, LIN28 is a sensitive (100% sensitivity) marker for primary extragonadal seminomas/germinomas, embryonal carcinomas, and yolk sac tumors with high specificity. Compared with SALL4, LIN28 demonstrated a similar level of diagnostic sensitivity for seminomas/germinomas and embryonal carcinomas. For primary extragonadal yolk sac tumors, although SALL4 stained all tumors (1+ in 1, 2+ in 2, 3+ in 10, and 4+ in 61), LIN28 stained more tumor cells (mean 95 vs 90%, P = 0.03) and was therefore more sensitive. For primary extragonadal yolk sac tumors, combining LIN28 and SALL4 can achieve a higher diagnostic sensitivity than either alone.


Assuntos
Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Mediastino/metabolismo , Neoplasias Embrionárias de Células Germinativas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Humanos , Imuno-Histoquímica , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia
3.
Cerebellum Ataxias ; 8(1): 10, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673860

RESUMO

BACKGROUND: Spinocerebellar Ataxia type 2 is a slowly progressive adult onset ataxia with a broad clinical presentation. CASE PRESENTATION: We describe a man with Spinocerebellar Ataxia type 2 with chronic, severe, and recurrent rhabdomyolysis, as part of the cerebellar ataxia genetic spectrum. Initially rhabdomyolysis was refractory to multiple medications, but entirely resolved and remained in chronic remission with pregabalin. CONCLUSIONS: This is the first report of Spinocerebellar Ataxia type 2 associated with chronic, severe, recurrent rhabdomyolysis as part of its genetic phenotype responsive to pregabalin.

4.
ACS Omega ; 6(35): 22700-22708, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34514241

RESUMO

Lateral flow immunoassays (LFIs) are simple, point-of-care diagnostic devices used for detecting biological agents or other analytes of interest in a sample. LFIs are predominantly singleplex assays, interrogating one target analyte at a time. There is a need for multiplex LFI devices, e.g., a syndromic panel to differentiate pathogens causing diseases exhibiting similar symptoms. Multiplex LFI devices would be especially valuable in instances where sample quantity is limiting and reducing assay time and costs is critical. There are limitations to the design parameters and performance characteristics of a multiplex LFI assay with many horizontal test lines due to constraints in capillary flow dynamics. To address some of the performance issues, we have developed a spot array multiplex LFI using Braille format (hence called Blind Spot) and a sensor, MACAW (Modular Automated Colorimetric Analyses Widget), that can analyze and interpret the results. As a proof of concept, we created a multiplex toxin panel, for detecting three toxins, using two letter codes for each. The results indicated that the six-plex, triple toxin assay performs as well as singleplex assays. The sensor-based calls are better compared to human interpretation in discriminating and interpreting ambiguous test results correctly especially at lower antigen concentrations and from strips with blemishes.

5.
Mod Pathol ; 22(12): 1628-36, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19820689

RESUMO

Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with alpha-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1+ (90%). Strong SALL4 staining was observed in all 49 germinomas (4+ in 48, 3+ in 1), 7 embryonal carcinomas (all 4+), and 27 yolk sac tumors (1+ in 1, 2+ in 2, 3+ in 7, 4+ in 17). SALL4 staining, 1+ weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4+ in all except 1 germinoma with 3+), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive alpha-fetoprotein staining (1+ in 9, 2+ in 7, 3+ in 5, and 4+ in 5). All yolk sac tumors showed positive glypican-3 staining (1+ in 6, 2+ in 6, 3+ in 7, and 4+ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with alpha-fetoprotein, and 63% with glypican-3 (P<0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than alpha-fetoprotein and glypican-3 for yolk sac tumors.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Sistema Nervoso Central/química , Neoplasias Embrionárias de Células Germinativas/química , Fatores de Transcrição/análise , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/patologia , Criança , Feminino , Glipicanas/análise , Humanos , Imuno-Histoquímica , Recém-Nascido , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Fator 3 de Transcrição de Octâmero/análise , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem , alfa-Fetoproteínas/análise
6.
J Med Case Rep ; 4: 308, 2010 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-20854655

RESUMO

INTRODUCTION: Cerebral amyloidoma is an infrequently recognized condition that can be confused with a more malignant etiology. Few cases have been reported. We present a case report and a review of the literature. CASE PRESENTATION: Our patient was a 64-year-old Caucasian man who was incidentally discovered to have a brain mass. He was found to have a cerebral amyloidoma. CONCLUSION: After discovery of the true etiology of his brain abnormality, it was determined that our patient had a more benign disease than was initially feared. Cases such as this demonstrate why consideration of this disorder is important.

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