25 research outputs found
Evolution of proteomic biomarker for chronic liver disease
Liver is the vital organ for synthesis of proteins whose concentration in blood reflects liver dysfunction. Variations in protein domain can generate clinically significant biomarkers. Biomarker pipeline includes discovery of candidates, qualification, verification, assay optimization, and validation. Advances in proteomic approach can discover protein biomarker candidates based on âup-or-downâ regulation or fold change in expression which is correlated with disease state. Despite numerous biomarker candidates been discovered, only few are useful in clinical practice which indicates the need for well-established validation regimen. Hence, the main purpose of this review is to understand the protein biomarker development and pitfalls. Companion diagnostics provide insights into potential cost-effective diagnosis for chronic liver disease
Copper-Catalyzed Sulfonyl AzideâAlkyne Cycloaddition Reactions: Simultaneous Generation and Trapping of CopperâTriazoles and âKetenimines for the Synthesis of Triazolopyrimidines
First
simultaneous generation and utilization of both copperâtriazole
and âketenimine intermediates in copper-catalyzed sulfonyl
azideâalkyne cycloaddition reactions is achieved for the one-pot
synthesis of triazolopyrimidines via a novel copper-catalyzed multicomponent
cascade of sulfonyl azides, alkynes, and azirines. Significantly,
the reaction proceeds under very mild conditions in good yields
Cirrhosis of liver: Interference of serpins in quantification of SERPINA4 â A preliminary study
Background: Cirrhosis of liver is a pathological condition, wherein functions of liver are impaired by chronic liver exploitations. Due to decrease in synthetic capacity, expressions of plasma proteins tend to decrease in blood stream. Serpins (Serine protease inhibitors) are class of plasma proteins expressed from liver with structural similarities and diverse functions. SERPINA4 (Kallistatin) is a multifunctional serpin clade A protein expressed from liver and concentration in serum is the reflection of extent of liver dysfunction. Objective: To identify interference of other serpins by immunological cross reactivity with SERPINA4 in cirrhotic liver and healthy subjects. Materials and methods: Blood samples were collected from 20 subjects (10 cirrhotic liver, 10 healthy) from R.L. Jalappa Hospital and Research Centre, Kolar, Karnataka, India. Separation of proteins was carried out by SDS-PAGE. Cross reactivity study was analyzed using western blot. Results: Proteins present in cirrhotic liver and healthy subject's serum were separated by SDS PAGE. There was no band detection on both (cirrhotic liver and healthy) PVDF (polyvinylidene diflouride) membranes. However, a significant band was observed with recombinant kallistatin. Conclusion: Structurally similar serpins with minor amino acid sequence similarities did not show any immunological cross reactivity with SERPINA4 due to non identical epitope in cirrhotic liver and healthy subjects. Present study revealed that there is no interference of serpins for immunological reactions in quantitative estimation of kallistatin which needs further validation
A proteomic approach of biomarker candidate discovery for alcoholic liver cirrhosis
Alcoholic liver disease (ALD) progresses from steatosis to alcoholic hepatitis to fibrosis and cirrhosis. Liver biopsy is considered as the gold standard method for diagnosis of liver cirrhosis and provides useful information about damaging process which is an invasive procedure with complications. Existing biomarkers in clinical practice have narrow applicability due to lack of specificity and lack of sensitivity. The objective of this article is to identify proteomic biomarker candidates for alcoholic liver cirrhosis by differential expression analysis between alcoholic liver cirrhotic and healthy subjects. Blood samples were collected from 20 subjects (10 alcoholic liver cirrhosis and 10 healthy) from R. L. Jalapa Hospital and Research Centre, Kolar, Karnataka, India. Differential protein analysis was carried out by two-dimensional electrophoresis after albumin depletion, followed by liquid chromatographyâmass spectrometry. The image analysis found 46 spots in cirrhotic gel and 69 spots in healthy gel, of which 14 spots were identified with significant altered expression levels. Based on the protein score and clinical significance, among 14 spots, a total of 28 protein biomarker candidates were identified: 13 with increased expression and 15 with decreased expression were categorized in alcoholic liver cirrhosis compared to healthy subjects. Protein biomarker candidates identified by â-omicsâ approach based on differential expression between alcoholic liver cirrhotic subjects and healthy subjects may give better insights for diagnosis of ALD. Prioritization of candidates identified is a prerequisite for validation regimen. Biomarker candidates require verification that demonstrates the differential expression will remain detectable by assay to be used for validation
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Abstract B123: Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (âOmicronâ) SARS-CoV-2 variant wave
Abstract Introduction: The SARS-CoV-2 (COVID-19) pandemic continues in the United States, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (âOmicronâ) COVID-19 variant wave. Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida from December 1st, 2021 through April 30th, 2022. After categorizing basic demographic factors for individuals whom tested positive for COVID-19 during the study timeframe, we analyzed additional risk factors leading to COVID-19 positivity including, but not limited to, vaccination status, previous COVID-19 positivity, and active receipt of chemotherapeutics. We then analyzed outcomes related to COVID-19, including treatment with advanced COVID-19 therapies such as oral or intravenous antivirals, monoclonal antibodies, convalescent plasma, steroids, or interleukin-6 inhibitors; interactions with inpatient services including emergency department (ED)/urgent care visits, inpatient and/or ICU admissions, and deaths from COVID-19. We finally assessed quality outcomes such as delay in cancer-directed therapy. This study was approved by the University of Miami IRB and Jackson Health System Clinical Trials Office. Results: 498 patients and 18 providers were retrospectively analyzed during the study timeframe. 49 patients tested positive for COVID-19 (9.84%), while 6 providers tested positive (33.3%) (p = 0.015). Patients whom tested positive were 51.0% female (n = 25), 26.5% Black (n = 13), 73.5% Hispanic/Latinx (n = 36), and 2.05% Asian (n = 1). Only 6.12% patients had tested positive for COVID-19 previously (n = 3), and 42.9% were considered unvaccinated (n = 21) while 14.3% were boosted (n = 7). 73.5% (n = 36) presented with symptomatic disease, 46.9% (n = 23) sought care at an ED/urgent care, 32.6% (n = 13) were admitted to the hospital, 6.12% were admitted to the ICU (n = 3), and 16.3% (n = 8) received advanced therapeutics. There were 2 (8.0%) COVID-19-related deaths (and another outside our study timeframe) among 23 non-COVID-19 related deaths in the patient population (p = 0.75). More than half of the patients whom tested positive experienced a cancer treatment delay (n = 27/49; 55.1%). Conclusions: The prevalence of COVID-19 positivity in our patient cohort during the initial Omicron wave mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. COVID-19 positivity conferred appreciable disparities in the presentation of disease as well as receipt of cancer treatment. COVID-19 positivity was more likely to result in symptomatic disease and ED/urgent care visit in cancer patients without previous COVID infection and unvaccinated status. COVID-19 accounted for 8.0% of our clinicâs total mortality. Citation Format: Aliya Khan, Samuel A. Kareff, Priscila Barreto-Coelho, Sunil Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, JosĂ© Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes. Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (âOmicronâ) SARS-CoV-2 variant wave [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B123