Biosensing of Alpha-Fetoprotein: A Key Direction toward the Early Detection and Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Rapid Colorimetric Quantita2tive Portable Platform for Detection of Brucella melitensis Based on a Fluorescence Resonance Energy Transfer Assay and Nanomagnetic Particles.

Brucellosis is a bacterial zoonotic disease that requires major attention for both health and financial facilities in many parts of the world including the Mediterranean and the Middle East. The existing gold standard diagnosis relies on the culturing technique, which is costly and time-consuming with a duration of up to 45 days. The Brucella protease biosensor represents a new detection approach that will lead to low-cost point-of-care devices for sensitive Brucella detection. In addition, the described diagnostic device is portable and simple to operate by a nurse or non-skilled clinician making it appropriate for the low-resource setting. In this study, we rely on the total extracellular protease proteolytic activity on specific peptide sequences identified using the FRET assay by high-throughput screening from the library of peptide (96 short peptides such as dipeptides and tripeptides) substrates for Brucella melitensis (B. melitensis). The B. melitensis-specific protease substrate was utilized in the development of the paper-based colorimetric assay. Two specific and highly active dipeptide substrates were identified (FITC-Ahx-K-r-K-Ahx-DABCYL and FITC-Ahx-R-r-K-Ahx-DABCYL). The peptide-magnetic bead nanoprobe sensors developed based on these substrates were able to detect the Brucella with LOD as low as 1.5 × 102 and 1.5 × 103 CFU/mL using K-r dipeptide and R-r dipeptide substrates, respectively, as the recognition element. The samples were tested using this sensor in few minutes. Cross-reactivity studies confirmed that the other proteases extracted from closely related pathogens have no significant effect on the sensor. To the best of our knowledge, this assay is the first assay that can be used with low-cost, rapid, direct, and visual detection of B. melitensis.

In Vivo Near-Infrared Fluorescence Resonance Energy Transfer (NIR-FRET) Imaging of MMP-2 in ALI/ARDS in LPS-Treated Mice.

Matrix metalloproteinases (MMPs) are zinc-dependent proteinases that are capable of cleavage of extracellular matrix (ECM) proteins and enzymes and play an important role in lung dysfunction. Specifically, MMP-2 is produced in the lung by alveolar epithelial and endothelial cells and other immune cells, such as macrophages. MMP-2 regulatory pathway is initiated in alveolar macrophages during acute lung injury (ALI), which may increase pulmonary inflammation. Therefore, there is a critical need for fast and reliable techniques to track the acute respiratory distress syndrome (ARDS). Here, we describe near-infrared fluorescence resonance energy transfer (NI-FRET) MMP-2-based probe for the in vivo detection of ALI induced by lipopolysaccharides (LPS). LPS-induced MMP-2 was measured using near-infrared (NIR) imaging after 1, 2, 4, 5, and 24 h of LPS exposure. Our results were compared with the data obtained from ELISA and Western blotting, demonstrating that MMP-2 fluorescence probe provide a promising in vivo diagnostic tool for ALI/ARDS in infected mice.

Low-Cost Point-of-Care Monitoring of ALT and AST Is Promising for Faster Decision Making and Diagnosis of Acute Liver Injury.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are important liver enzymes in clinical settings. Their levels are known to be elevated in individuals with underlying liver diseases and those consuming hepatotoxic drugs. Serum ALT and AST levels are crucial for diagnosing and assessing liver diseases. Serum ALT is considered the most reliable and specific candidate as a disease biomarker for liver diseases. ALT and AST levels are routinely analyzed in high-risk individuals for the bioanalysis of both liver function and complications associated with drug-induced liver injury. Typically, ALT and AST require blood sampling, serum separation, and testing. Traditional methods require expensive or sophisticated equipment and trained specialists, which is often time-consuming. Therefore, developing countries have limited or no access to these methods. To address the above issues, we hypothesize that low-cost biosensing methods (paper-based assays) can be applied to the analysis of ALT and AST levels in biological fluids. The paper-based biodetection technique can semi-quantitatively measure ALT and AST from capillary finger sticks, and it will pave the way for the development of an inexpensive and rapid alternative method for the early detection and diagnosis of liver diseases. This method is expected to significantly reduce the economic burden and aid routine clinical analysis in both developed and underdeveloped countries. The development of low-cost testing platforms and their diagnostic utility will be extremely beneficial in helping millions of patients with liver disorders.

Development of Rapid Aptamer-Based Screening Assay for the Detection of Covid-19 Variants.

The development of a colorimetric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection assay with the WHO published ASSURED criteria is reported, in which the biosensor should have the following characteristics of (i) being affordable for low-income communities, (ii) sensitive, (iii) specific, (iv) user-friendly to be used by non-skilled personnel, (v) rapid and robust, (vi) equipment-free, and (vii) delivered to the end-users as a simple and easy to use point-of-care tool. Early viral infection detection prevents virus spread and controls the epidemic. We herein report the development of a colorimetric assay in which SARS-COV-2 variants can be detected by colorimetric observation of color on the sensing cotton swab surface. Using the developed biosensor assay, it is possible to discriminate between the various SARS-CoV-2 variants with a LOD of 100 ng/mL within 4 min including sample preconcentration and incubation step. The results illustrated the development of a SARS-CoV-2 colorimetric biosensor that can be mass produced, with low-reagent cost, and can be read-out visually in the field by nonskilled personnel.

Paper-Based Biosensor for the Detection of Sepsis Using MMP-9 Biomarker in FIP Mice Model.

Sepsis is an immune response to a microbial invasion that causes organ injury and dysfunction due to a systemic inflammatory response. Sepsis is a serious, life-threatening condition and a widely recognized global health challenge. Given its high death rate, it is critical to diagnose sepsis and start treatment as early as possible. There is an urgent need for a sensitive and rapid screening method for detecting sepsis. In this study, we investigated the use of MMP-9 as a biomarker for sepsis. A colorimetric paper-based biosensor was used for the detection of MMP-9 utilizing peptide-magnetic nanoparticle conjugates. The method is based on the cleavage of the MMP-9-specific peptide by the protease leading to the detaching of the magnetic beads from the sensor surface and changing of color. A fecal intraperitoneal (FIP) challenge was used to induce sepsis in mice, and an MMP-9 secretion was measured by taking blood and Bronchoalveolar Lavage (BAL) fluid samples at 1 h, 2 h, 4 h, and 20 h (early sepsis) post-challenge intervals. The results of the paper-based sensor for the detection of MMP-9 levels in blood samples and BAL samples were compared with ELISA and Western Blot. We found that both blood and BAL levels of MMP-9 increased immediately and could be detected as early as 1 h in FIP mice post-challenge. Our work adds evidence to the assertion that MMP-9 is a reliable biomarker for the detection of sepsis at early stages.

Biosensing Platform for the Detection of Biomarkers for ALI/ARDS in Bronchoalveolar Lavage Fluid of LPS Mice Model.

Acute respiratory distress syndrome (ARDS) is a worldwide health concern. The pathophysiological features of ALI/ARDS include a pulmonary immunological response. The development of a rapid and low-cost biosensing platform for the detection of ARDS is urgently needed. In this study, we report the development of a paper-based multiplexed sensing platform to detect human NE, PR3 and MMP-2 proteases. Through monitoring the three proteases in infected mice after the intra-nasal administration of LPS, we showed that these proteases played an essential role in ALI/ARDS. The paper-based sensor utilized a colorimetric detection approach based on the cleavage of peptide-magnetic nanoparticle conjugates, which led to a change in the gold nanoparticle-modified paper sensor. The multiplexing of human NE, PR3 and MMP-2 proteases was tested and compared after 30 min, 2 h, 4 h and 24 h of LPS administration. The multiplexing platform of the three analytes led to relatively marked peptide cleavage occurring only after 30 min and 24 h. The results demonstrated that MMP-2, PR3 and human NE can provide a promising biosensing platform for ALI/ARDS in infected mice at different stages. MMP-2 was detected at all stages (30 min-24 h); however, the detection of human NE and PR3 can be useful for early- (30 min) and late-stage (24 h) detection of ALI/ARDS. Further studies are necessary to apply these potential diagnostic biosensing platforms to detect ARDS in patients.

Emerging Biosensing Methods to Monitor Lung Cancer Biomarkers in Biological Samples: A Comprehensive Review.

Lung cancer is the most commonly diagnosed of all cancers and one of the leading causes of cancer deaths among men and women worldwide, causing 1.5 million deaths every year. Despite developments in cancer treatment technologies and new pharmaceutical products, high mortality and morbidity remain major challenges for researchers. More than 75% of lung cancer patients are diagnosed in advanced stages, leading to poor prognosis. Lung cancer is a multistep process associated with genetic and epigenetic abnormalities. Rapid, accurate, precise, and reliable detection of lung cancer biomarkers in biological fluids is essential for risk assessment for a given individual and mortality reduction. Traditional diagnostic tools are not sensitive enough to detect and diagnose lung cancer in the early stages. Therefore, the development of novel bioanalytical methods for early-stage screening and diagnosis is extremely important. Recently, biosensors have gained tremendous attention as an alternative to conventional methods because of their robustness, high sensitivity, inexpensiveness, and easy handling and deployment in point-of-care testing. This review provides an overview of the conventional methods currently used for lung cancer screening, classification, diagnosis, and prognosis, providing updates on research and developments in biosensor technology for the detection of lung cancer biomarkers in biological samples. Finally, it comments on recent advances and potential future challenges in the field of biosensors in the context of lung cancer diagnosis and point-of-care applications.

Assessing the knowledge and attitude towards HIV/AIDS among the general population and health care professionals in MENA region.

INTRODUCTION: Human Immunodeficiency Virus infection continue to represent a global health concern influenced by various social, economic, and cultural factors. The MENA are among the top regions in the world with the fastest-growing HIV epidemic. Thus, adequate knowledge and a positive attitude of people toward HIV/AIDS are of utmost importance to prevent the spreading of the disease. Accordingly, this study aims to evaluate the knowledge and attitude of the public and healthcare population toward HIV/AIDs. METHODS: A cross-sectional analysis was conducted among residents within our population from October 2018 until August 2019. An anonymous online questionnaire was used to investigate the population's demographic characteristics, HIV/AIDS-related knowledge, and attitudes toward HIV-infected patients. Participants completed a 40-item questionnaire designed to measure their knowledge and attitude toward HIV/AIDS. The data was collected via surveys, administered through electronic tablets to the participants at public places (n = 5,757) and through an online version of the questionnaire on Google Forms (n = 2500), which was sent through social media platforms. Descriptive statistics were used to analyse the data using the R-statistical software program. RESULTS: A total of 8,257 participants were included in our analysis. Saudi Arabian citizens represented 79% of the participants, while participants from the MENA countries represented 11.7% and 3% from the other Gulf Cooperation Council countries. Fifty-nine (59%) knew that HIV is a contagious infection, and 13.8% were unaware that HIV could be transmitted sexually. A few healthcare professionals reported negative attitudes toward HIV infected patients. Many risk factors, including age, gender, nationality, and education, significantly affected the knowledge and attitude scores. In this survey, we found that social media is the primary source of participants' information. CONCLUSIONS: Overall correct knowledge score of individuals about HIV/AIDS was relatively low. This study showed that the general population was knowledgeable to a certain degree about HIV/AIDS and its modes of transmission. Nevertheless, they lack a detailed understanding of the disease's nature, modes of transmission, and existing treatment. Policymakers in the region should further eliminate social discrimination and stigma in HIV-infected patients.

Aptasensors Are Conjectured as Promising ALT and AST Diagnostic Tools for the Early Diagnosis of Acute Liver Injury.

Abnormal levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in human serum are the most sensitive indicator of hepatocellular damage. Because liver-related health problems are directly linked to elevated levels of ALT and AST, it is important to develop accurate and rapid methods to detect these enzymes for the early diagnosis of liver disease and prevention of long-term liver damage. Several analytical methods have been developed for the detection of ALT and AST. However, these methods are based on complex mechanisms and require bulky instruments and laboratories, making them unsuitable for point-of-care application or in-house testing. Lateral flow assay (LFA)-based biosensors, on the other hand, provide rapid, accurate, and reliable results, are easy to operate, and are affordable for low-income populations. However, due to the storage, stability, batch-to-batch variations, and error margins, antibody-based LFAs are considered unaffordable for field applications. In this hypothesis, we propose the selection of aptamers with high affinity and specificity for the liver biomarkers ALT and AST to build an efficient LFA device for point-of-care applications. Though the aptamer-based LFA would be semiquantitative for ALT and AST, it would be an inexpensive option for the early detection and diagnosis of liver disease. Aptamer-based LFA is anticipated to minimize the economic burden. It can also be used for routine liver function tests regardless of the economic situation in each country. By developing a low-cost testing platform, millions of patients suffering from liver disease can be saved.

Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems.

Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body's first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.

A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome. OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS. DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19. METHODS: Data on trial characteristics and intervention characteristics were collected and summarized. RESULTS: After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed. CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.

A Hypothetical Approach to Concentrate Microorganisms from Human Urine Samples Using Paper-Based Adsorbents for Point-of-Care Molecular Assays.

This hypothesis demonstrates that the efficiency of loop-mediated isothermal amplification (LAMP) for nucleic acid detection can be positively influenced by the preconcentration of microbial cells onto hydrophobic paper surfaces. The mechanism of this model is based on the high affinity of microbes towards hydrophobic surfaces. Extensive studies have demonstrated that hydrophobic surfaces exhibit enhanced bacterial and fungal adhesion. By exploiting this inherent affinity of hydrophobic paper substrates, the preconcentration approach enables the adherence of a greater number of target cells, resulting in a higher concentration of target templates for amplification directly from urine samples. In contrast to conventional methods, which often involve complex procedures, this approach offers a simpler, cost-effective, and user-friendly alternative. Moreover, the integration of cell adhesion, LAMP amplification, and signal readout within paper origami-based devices can provide a portable, robust, and highly efficient platform for rapid nucleic acid detection. This innovative hypothesis holds significant potential for point-of-care (POC) diagnostics and field surveillance applications. Further research and development in this field will advance the implementation of this technology, contributing to improved healthcare systems and public health outcomes.

Development of a Rapid Immuno-Based Screening Assay for the Detection of Adenovirus in Eye Infections.

Despite progress in fighting infectious diseases, human pathogenesis and death caused by infectious diseases remain relatively high worldwide exceeding that of cancer and cardiovascular diseases. Human adenovirus (HAdV) infects cells of the upper respiratory tract causing flu-like symptoms that are accompanied by pain and inflammation. Diagnosis of HAdV is commonly achieved by conventional methods such as viral cultures, immunoassays, and polymerase chain reaction (PCR) techniques. However, there are a variety of problems with conventional methods including slow isolation and propagation, inhibition by neutralizing antibodies, low sensitivity of immunoassays, and the diversity of HAdV strains for the PCR technique. Herein, we report the development and evaluation of a novel, simple, and reliable nanobased immunosensing technique for the rapid detection of human adenoviruses (HAdVs) that cause eye infections. This rapid and low-cost assay can be used for screening and quantitative tests with a detection limit of 102 pfu/mL in less than 2 min. The sensing platform is based on a sandwich assay that can detect HAdVs visually by a color change. Sensor specificity was demonstrated using other common viral antigens, including Flu A, Flu B, coronavirus (COV), and Middle East respiratory syndrome coronavirus (MERS COV). This cotton-based testing device potentially exhibits many of the desired characteristics of a suitable point-of-care and portable test, which can be carried out by nurses or clinicians especially for low-resource settings.

Aptamers: Potential Diagnostic and Therapeutic Agents for Blood Diseases.

Aptamers are RNA/DNA oligonucleotide molecules that specifically bind to a targeted complementary molecule. As potential recognition elements with promising diagnostic and therapeutic applications, aptamers, such as monoclonal antibodies, could provide many treatment and diagnostic options for blood diseases. Aptamers present several superior features over antibodies, including a simple in vitro selection and production, ease of modification and conjugation, high stability, and low immunogenicity. Emerging as promising alternatives to antibodies, aptamers could overcome the present limitations of monoclonal antibody therapy to provide novel diagnostic, therapeutic, and preventive treatments for blood diseases. Researchers in several biomedical areas, such as biomarker detection, diagnosis, imaging, and targeted therapy, have widely investigated aptamers, and several aptamers have been developed over the past two decades. One of these is the pegaptanib sodium injection, an aptamer-based therapeutic that functions as an anti-angiogenic medicine, and it is the first aptamer approved by the U.S. Food and Drug Administration (FDA) for therapeutic use. Several other aptamers are now in clinical trials. In this review, we highlight the current state of aptamers in the clinical trial program and introduce some promising aptamers currently in pre-clinical development for blood diseases.

The current global perspective of the knowledge-attitude-behavior of the general public towards the corona virus disease -19 pandemic: Systematic review and meta-analysis on 67,143 participants.

BACKGROUND: Determining the success of infectious disease outbreak prevention is dependent mainly on public knowledge and compliance regarding the guidelines of precautionary behaviors and practices. While the current literature about the COVID-19 pandemic extensively addresses clinical and laboratory-based studies, a gap remains still present in terms of evaluating the general public knowledge and behaviors towards the COVID-19 pandemic. The aim of this review was to form a preliminary and contemporary understanding of the general public knowledge, attitude, and behaviors towards the COVID-19 pandemic globally. METHODS: A systematic search was conducted in various databases until May 2020. Each study's characteristics including the sample size, region, and study type were examined individually. A meta-analysis with a random-effects model and pooled prevalence with 95% confidence interval (CI) of all evaluated outcomes such as adequate knowledge, positive feelings, worrisome about the COVID-19 pandemic, and practice were recorded and reported from each study. Parameters such as random distribution, blinding, incomplete outcome data, selective reporting, and other biases were utilized to assess the quality of each retrieved record. Both Begg's and Egger's tests were employed to evaluate symmetry of funnel plots for assessment of publication bias. The overall quality of evidence was evaluated using GRADEpro software. RESULTS: A total of 26 studies with 67,143 participants were analyzed. The overall prevalence of knowledge, positive attitude, worrisome, and practice of precautionary measures were 0.87 (95%CI, 0.84-0.89), 0.85 (95%CI, 0.77-0.92), 0.71 (95%CI, 0.61-0.81), and 0.77 (95%CI, 0.70-0.83), respectively. Subgroup analysis demonstrated that social distancing was less practiced in Africa than other regions (p = 0.02), while knowledge of prevention of COVID-19 was reported higher in Asia (p = 0.001). Furthermore, people in developing countries had a higher prevalence of worrisome towards the COVID-19 pandemic with a p-value of less than 0.001. The quality of evidence was noted to be of low certainty in practice domain but moderate in the remaining outcomes. CONCLUSION: Assessing the public's risk perception and precautionary behaviors is essential in directing future policy and health population research regarding infection control and preventing new airborne disease outbreaks.

Combination of Carbon Nanofiber-Based Electrochemical Biosensor and Cotton Fiber: A Device for the Detection of the Middle-East Respiratory Syndrome Coronavirus.

The miniaturization of biosensors for point-of-care diagnosis is highly important in infection control. Electrochemical biosensors offer several advantages in diagnosis in terms of cost, disposability, portability, and sensitivity. Here, a miniaturized electrochemical immunosensor combined with cotton fiber for the detection of the Middle-East respiratory syndrome coronavirus (MERS-CoV) is described. Taking advantage of the absorption capability of cotton, the nasal and saliva samples can be collected and directly transferred to the immunosensor surface for detection using a single tool. The immunosensor was fabricated on a disposable screen-printed electrode precoated with carbon nanofibers. The electrodes were functionalized with carboxyphenyl groups that were used for the immobilization of the spike protein of the MERS-CoV. A competitive detection scheme was employed using the antibody for the MERS-CoV spike protein, and the square-wave voltammetry technique was used for measurements. The biosensor tested after the cotton coating of the electrode exhibited excellent performance. The biosensor was capable of detecting the MERS-CoV spike protein within a concentration range from 0.1 pg·mL-1 to 1 µg·mL-1 with a limit of detection of 0.07 pg·mL, implying the high sensitivity of the method. The immunosensor did not exhibit any cross-reactivity against proteins from HCoV and Influenza A, indicating the excellent selectivity of this approach. Testing of the biosensor in nasal samples showed very high recovery percentages. This disposable biosensor can be used as a miniaturized device for the collection of samples and detection of the virus using a portable potentiostat connected to a smartphone.

COVID-19: Lung-Centric Immunothrombosis.

The respiratory tract is the major site of infection by SARS-CoV-2, the virus causing COVID-19. The pulmonary infection can lead to acute respiratory distress syndrome (ARDS) and ultimately, death. An excessive innate immune response plays a major role in the development of ARDS in COVID-19 patients. In this scenario, activation of lung epithelia and resident macrophages by the virus results in local cytokine production and recruitment of neutrophils. Activated neutrophils extrude a web of DNA-based cytoplasmic material containing antimicrobials referred to as neutrophil extracellular traps (NETs). While NETs are a defensive strategy against invading microbes, they can also serve as a nidus for accumulation of activated platelets and coagulation factors, forming thrombi. This immunothrombosis can result in occlusion of blood vessels leading to ischemic damage. Herein we address evidence in favor of a lung-centric immunothrombosis and suggest a lung-centric therapeutic approach to the ARDS of COVID-19.

Low-cost colorimetric diagnostic screening assay for methicillin resistant Staphylococcus aureus.

The timely diagnosis of MRSA in clinical samples helps to reduce the attendant morbidity/mortality associated with infection due to the organism. The early institution of appropriate therapy or deployment of infection control protocols are dependent on a timely report from the microbiology laboratory. Various assays currently used in the identification of MRSA are associated with inherent shortcomings, thus there is a need to explore newer diagnostic frontiers that can eliminate some of these short comings at a relatively cheap, timely, specific and sensitive manner. We present in this study a MRSA specific optical immunosensor to detect the presence of the pathogen on contaminated surface using control and patient strains. Results revealed a detection limits of 103 CFU mL-1 upon visual observation, and 29 CFU mL-1 as determined by the linear regression equation, following the use of ImageJ to quantify activated cotton swab color intensity. The specificity of the sensor was examined by blind testing a panel of non-MRSA bacteria (E. coli, S. aureus and S. epidermis). Negative visual read-out was observed for all tested non-specific bacteria except for MRSA. Assay takes an average of 5 min and presents a powerful point-of-care diagnostic platform for the detection of MRSA.

Aptasensor for the detection of Methicillin resistant Staphylococcus aureus on contaminated surfaces.

There is mounting evidence that contaminated hospital environment plays a crucial role in the transmission of nosocomial pathogens such as MRSA. The institution of infection control protocols is predicated on the early laboratory detection of the pathogen from relevant samples. Processing of environmental samples for the presence of bacterial contaminants in the clinical environment is poorly standardized when compared with analysis of clinical samples. The various laboratory methods available for processing environmental samples are difficult to standardized and most require a long turnaround time before results are available. In this study, we present a report of the performance of a novel pathogen aptasensor swab designed to qualitatively and quantitatively detect MRSA, on contaminated non-absorbable surfaces. The visual detection limit of the MRSA aptasensor swab was less than 100 CFU/ml and theoretically using a standard curve, was 2 CFU/ml. A relatively short turnaround time of 5 min was established for the assay while the linear range of quantitation was 102-105 CFU/ml. Engineered aptasensor targets MRSA selectively and binds to none of the other tested bacterial pathogen, on a multi-contaminated surface. This novel detection tool was easy to use and relatively cheap to produce.