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.
To systematically review registered trials currently investigating therapeutic modalities for PACS.
A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform.
Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.
Data on trial characteristics and intervention characteristics were collected and summarized.
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.
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.
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.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights ► In children <5 years in KSA from 2005 to 2010, the most frequently isolated IPD serotypes were 23F, 19F, 6B, 5 and 1. ► There was significant rise of serotypes 19A in the last 2 years in ...KSA and a notable decrease in serotype 18C. ► Serotype coverage for PCV7, PCV10, PCV13 in children <5 years was 53%, 80%, and 91% from 2005 to 2010. ► Antibiotic resistance levels remained high but did not notably increase from 2005 to 2010. ► Continued surveillance is critical to measure the emergence of new pneumococcal serotypes and antibiotic resistance strains.
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.
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.
Sickle cell Anemia (SCA) is a widespread disease that causes hemolysis of blood cells, anemia, painful episodes, organ damage, and in some cases death. Early diagnosis of sickle cell anemia is ...significantly useful to reduce the mortality rate and manage the disease effectively. Here, we report the selection and characterization of specific aptamers against hemoglobin A (HbA) and hemoglobin S (HbS) and their integration into the electrochemical sensing platforms. The aptamers which have the highest binding affinities toward HbA and HbS are HbA17 and HbS 4 with dissociation constants of 13.5 and 57.5 nM, respectively. Thiol-modified aptamers were immobilized on screen-printed gold electrodes (Au-SPE) and used for the label-free detection of HbA and HbS using square wave voltammetry. The voltammetric aptasensors showed high selectivity and specificity toward HbA and HbS. A cross-reactivity tests were performed showing no response when the aptasensors were incubated with the nonspecific hemoglobin. This method enabled the detection of HbA and HbS in human whole blood showing good agreement with the electrophoresis method. This suggests a great promise of this platform for differentiating between healthy individuals (HbAA), patients with sickle-cell disease (HbSS) and carriers (HbAS).
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.
COVID-19: Lung-Centric Immunothrombosis Kvietys, Peter R; Fakhoury, Hana M A; Kadan, Sana ...
Frontiers in cellular and infection microbiology,
06/2021, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
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.
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.