ABSTRACT
We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagnosing pathogen-associated infections, empowered by an illustrative novel methodology that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse transcription cum amplification protocol for detecting viral RNA. In a point-of-care format, this test is executable in a unified single-step, single-chamber procedure, leading to seamless sample-to-result integration in an inexpensive, scalable, pre-programmable, and customizable portable device, with mobile-app-integrated interpretation and analytics involving minimal manually operative procedures. The test exhibited a high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection by the Indian Council of Medical Research (ICMR), and subsequently using 170 double-blind patient samples in a point-of-care format outside controlled laboratory settings as performed by unskilled technicians in an organized clinical trial. We also established its efficacy in detecting Influenza A infection by performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based molecular diagnostic procedures and the elegance of common rapid tests renders the method ideal for deployment in resource-limited settings towards catering the needs of the underserved.
Subject(s)
COVID-19 , Communicable Diseases , Humans , Point-of-Care Systems , RNA, Viral/genetics , SARS-CoV-2ABSTRACT
Imatinib, the first Tyrosine Kinase Inhibitor (TKI) used for the treatment of chronic myeloid leukaemia (CML) has revolutionized the management by inhibiting BCR-ABL tyrosine kinase. According to earlier reports there are concerns regarding the adverse effect of imatinib on haemostasis by causing platelet dysfunction. Here we studied platelet function using platelet aggregometry, in 19 CML chronic phase (CML-CP) patients on imatinib therapy, in complete haematologic response (CHR). The median duration of imatinib therapy before performing the test was 154 days. This study reveals that there are large inter-individual variations in platelet functions among imatinib treated patients and different levels of variability have been seen for different agonists. Most common aggregation abnormality (< 50% aggregation) was seen with low dose collagen (1 µg/ml) in 31.57% patients. Despite in-vitro platelet aggregation defects, none of the patients showed any bleeding symptoms. This enigma can possibly be explained by the fact that platelet specific agonists, epinephrine and collagen act in synergy for platelet aggregation compared against individual low dose agonists, supported by ex-vivo experiments in normal healthy control group (n = 5) (p value < 0.0004 for epinephrine, p value < 0.0001 for collagen). This experiment was also confirmed in a CML-CP patient. In future, more studies are needed to find out the exact mechanism of this inhibition.
ABSTRACT
Inherited macrothrombocytopenia is increasingly being recognized as a relatively common condition. This descriptive review aims at focusing on the different areas of advancement that have taken place with this condition with particular reference to India. A pubmed search of articles between January 1990 and October 2017 with the key words-macrothrombocytopenia, asymptomatic macrothrombocytopenia, macrothrombocytopenia India, syndromic macrothrombocytopenia, molecular pathology, megakaryopoiesis and platelet formation were searched. The shortlisted articles were then read. Review articles provided additional references and the articles thus obtained were also read. Special interest and research conducted by the authors provided further sources of information. A total of 487 articles were found of which 68 articles were related to our subject of review. Review articles were read and additional articles from the reference quoted. Forty-four percent of nonsyndromic Inherited macrothrombocytopenia showed mutations of MYH9, GP1BB, GP1Ba, GPIX, ABCG5 and 8, ACTN, FLI, TUBB and RUNX1 frequently in heterozygous state. All types of inheritance pattern namely autosomal dominant, recessive and sex linked patterns have been described. Syndromic causes of this phenomenon are well known and have been described. Many asymptomatic patients do have mild or moderate bleeding history. Clinical algorithms to differentiate chronic ITP associated macrothrombocytopenia from inherited variety have been explored. Inherited macrothrombocytopenia is an emerging area of interest in platelet biology with its implication in diagnosis, prognosis, genetic counseling, management and in transfusion medicine.
