Detection of Intravascular Hemolysis in Newborn Infants Using Urinary Carbonic Anhydrase I Immunoreactivity

Abstract Background Mild hemolysis occurs physiologically in neonates, but more severe forms can lead to life-threatening anemia. Newborns in developing regions are particularly at-risk due to the higher incidence of triggers (protozoan infections, sepsis, certain genetic traits). In advanced healthcare facilities, hemolysis is monitored indirectly using resource-intensive methods that probe downstream ramifications. These approaches could potentially delay critical decisions in early-life care, and are not suitable for point-of-care testing. Rapid and cost-effective testing could be based on detecting red blood cell (RBC)-specific proteins, such as carbonic anhydrase I (CAI), in accessible fluids (e.g., urine). Methods Urine was collected from 26 full-term male neonates and analyzed for CAI using immunoassays (ELISA, western blot) and proteomics (mass spectrometry). The cohort included a range of hemolytic states, including admissions with infection, ABO incompatibility, and receiving phototherapy. Data were paired with hemoglobin, serum bilirubin (SBR), and C-reactive protein (CRP) measurements. Results Urine from a control cohort (CRP < 20 mg/L, SBR < 125µmol/L) had no detectable CAI, in line with results from healthy adults. CAI excretion was elevated in neonates with raised SBR (>125 µmol/L), including those qualifying for phototherapy. Newborns with low SBR (<125 µmol/L) but elevated CRP (>20 mg/L) produced urine with strong CAI immunoreactivity. Proteomics showed that CAI was the most abundant RBC-specific protein in CAI-immunopositive samples, and did not associate with other RBC-derived peptides, indicating an intravascular hemolytic source followed by CAI-selective excretion. Conclusions CAI is a direct biomarker of intravascular hemolysis that can be measured routinely in urine using non-invasive methods under minimal-laboratory conditions.

Download Full-text

Accessibility of Point-of-Care Diagnostic Services for Maternal Health in Lower Healthcare Facilities in Northern Ghana: A Cross-Sectional Survey

SSRN Electronic Journal ◽

10.2139/ssrn.3204717 ◽

2018 ◽

Cited By ~ 1

Author(s):

Desmond Kuupiel ◽

Boikhutso Tlou ◽

Vitalis Bawontuo ◽

Tivani P. Mashamba-Thompson

Keyword(s):

Maternal Health ◽

Point Of Care ◽

Northern Ghana ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Healthcare Facilities

Download Full-text

Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

Diagnostics ◽

10.3390/diagnostics11081352 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1352

Author(s):

Darius Riziki Martin ◽

Nicole Remaliah Sibuyi ◽

Phumuzile Dube ◽

Adewale Oluwaseun Fadaka ◽

Ruben Cloete ◽

...

Keyword(s):

Low Income ◽

Point Of Care ◽

Health Care Systems ◽

Cost Effective ◽

Rapid Screening ◽

Low Income Countries ◽

Sputum Smear ◽

Diagnostic Systems ◽

Molecular Tests ◽

Rapid Tests

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.

Download Full-text

Longitudinal remotely mentored self-performed lung ultrasound surveillance of paucisymptomatic Covid-19 patients at risk of disease progression

The Ultrasound Journal ◽

10.1186/s13089-021-00231-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Andrew W. Kirkpatrick ◽

Jessica L. McKee ◽

John M. Conly

Keyword(s):

At Risk ◽

Lung Ultrasound ◽

Point Of Care ◽

Human Life ◽

Vital Signs ◽

Home Monitoring ◽

Cost Effective ◽

Care Providers ◽

Vital Signs Monitoring ◽

Ultrasound Probes

AbstractCOVID-19 has impacted human life globally and threatens to overwhelm health-care resources. Infection rates are rapidly rising almost everywhere, and new approaches are required to both prevent transmission, but to also monitor and rescue infected and at-risk patients from severe complications. Point-of-care lung ultrasound has received intense attention as a cost-effective technology that can aid early diagnosis, triage, and longitudinal follow-up of lung health. Detecting pleural abnormalities in previously healthy lungs reveal the beginning of lung inflammation eventually requiring mechanical ventilation with sensitivities superior to chest radiographs or oxygen saturation monitoring. Using a paradigm first developed for space-medicine known as Remotely Telementored Self-Performed Ultrasound (RTSPUS), motivated patients with portable smartphone support ultrasound probes can be guided completely remotely by a remote lung imaging expert to longitudinally follow the health of their own lungs. Ultrasound probes can be couriered or even delivered by drone and can be easily sterilized or dedicated to one or a commonly exposed cohort of individuals. Using medical outreach supported by remote vital signs monitoring and lung ultrasound health surveillance would allow clinicians to follow and virtually lay hands upon many at-risk paucisymptomatic patients. Our initial experiences with such patients are presented, and we believe present a paradigm for an evolution in rich home-monitoring of the many patients expected to become infected and who threaten to overwhelm resources if they must all be assessed in person by at-risk care providers.

Download Full-text

Point of Care Diagnostics in the Age of COVID-19

Diagnostics ◽

10.3390/diagnostics11010009 ◽

2020 ◽

Vol 11 (1) ◽

pp. 9

Author(s):

Meysam Rezaei ◽

Sajad Razavi Bazaz ◽

Sareh Zhand ◽

Nima Sayyadi ◽

Dayong Jin ◽

...

Keyword(s):

Point Of Care ◽

Diagnostic Methods ◽

Global Public Health ◽

Current Standard ◽

Healthcare Facilities ◽

Major Threat ◽

Point Of Care Diagnostics ◽

Recent Outbreak ◽

Control Virus ◽

Biosafety Level

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.

Download Full-text

3D Printed Imaging Platform for Portable Cell Counting

The Analyst ◽

10.1039/d1an00778e ◽

2021 ◽

Author(s):

Diwakar M. Awate ◽

Cicero C. Pola ◽

Erica Shumaker ◽

Carmen L Gomes ◽

Jaime Javier Juarez

Keyword(s):

3D Printing ◽

Point Of Care ◽

Cost Effective ◽

Cell Counting ◽

Biomedical Sciences ◽

Widespread Application ◽

Resource Limited ◽

Cost Effective Approach ◽

3D Printed

Despite having widespread application in the biomedical sciences, flow cytometers have several limitations that prevent their application to point-of-care (POC) diagnostics in resource-limited environments. 3D printing provides a cost-effective approach...

Download Full-text

Direct diagnostic testing of SARS-CoV-2 without the need for prior RNA extraction

Scientific Reports ◽

10.1038/s41598-021-81487-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shan Wei ◽

Esther Kohl ◽

Alexandre Djandji ◽

Stephanie Morgan ◽

Susan Whittier ◽

...

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Diagnostic Testing ◽

Rna Extraction ◽

Cost Effective ◽

Clinical Samples ◽

Nasopharyngeal Swab ◽

Percentage Agreement ◽

Testing Method ◽

Viral Transport

AbstractThe COVID-19 pandemic has resulted in an urgent need for a rapid, point of care diagnostic testing that could be rapidly scaled on a worldwide level. We developed and tested a highly sensitive and robust assay based on reverse transcription loop mediated isothermal amplification (RT-LAMP) that uses readily available reagents and a simple heat block using contrived spike-in and actual clinical samples. RT-LAMP testing on RNA-spiked samples showed a limit of detection (LoD) of 2.5 copies/μl of viral transport media. RT-LAMP testing directly on clinical nasopharyngeal swab samples in viral transport media had an 85% positive percentage agreement (PPA) (17/20), and 100% negative percentage agreement (NPV) and delivered results in 30 min. Our optimized RT-LAMP based testing method is a scalable system that is sufficiently sensitive and robust to test for SARS-CoV-2 directly on clinical nasopharyngeal swab samples in viral transport media in 30 min at the point of care without the need for specialized or proprietary equipment or reagents. This cost-effective and efficient one-step testing method can be readily available for COVID-19 testing world-wide, especially in resource poor settings.

Download Full-text

Autoimmune phenomena and spontaneous tumour regression. The role of carbonic anhydrase I

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16525 ◽

2021 ◽

Author(s):

Lenka Minichová ◽

Ľudovít Škultéty ◽

Ján Lakota

Keyword(s):

Carbonic Anhydrase ◽

Tumour Regression ◽

Carbonic Anhydrase I ◽

Autoimmune Phenomena

Download Full-text

Synthesis and Human Carbonic Anhydrase I, II, IX, and XII Inhibition Studies of Sulphonamides Incorporating Mono-, Bi- and Tricyclic Imide Moieties

Pharmaceuticals ◽

10.3390/ph14070693 ◽

2021 ◽

Vol 14 (7) ◽

pp. 693

Author(s):

Kalyan K. Sethi ◽

KM Abha Mishra ◽

Saurabh M. Verma ◽

Daniela Vullo ◽

Fabrizio Carta ◽

...

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

Docking Studies ◽

Carbonic Anhydrases ◽

Molecular Docking Studies ◽

Structure Activity Relationships ◽

Structure Activity ◽

Carbonic Anhydrase I ◽

Human Carbonic Anhydrase ◽

Inhibition Studies

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure–activity relationships (SAR) are rationalised with the help of molecular docking studies.

Download Full-text

Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-019-51837-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Aidan Kenny ◽

Eva M. Jiménez-Mateos ◽

María Ascensión Zea-Sevilla ◽

Alberto Rábano ◽

Pablo Gili-Manzanaro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Unmet Need ◽

Cost Effective ◽

Specific Protein ◽

Tear Fluid ◽

Initiation Factor ◽

Non Invasive ◽

A Genome ◽

Potential Biomarker

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.

Download Full-text