Project description:E-cigarette use has been increasing globally over the past decade. Many use e-cigarettes as an alternative or method to quit cigarette smoking, whereas others use these products recreationally. As technology has advanced, many individuals have reported symptoms of dependence on these products and continue to use them beyond achieving abstinence from smoking. Despite individuals reporting interest in quitting, little is known about e-cigarette cessation. This systematic review sought to identify and evaluate all human subjects literature published on the outcome of e-cigarette cessation through September 2021. Of the 79 articles identified, 56 were cross-sectional, 6 were qualitative, 5 were cohort studies, 3 were experimental, 2 were mixed methods, and 7 reported intervention or case studies of e-cigarette cessation. Results showed youth generally had high intent to quit e-cigarettes, whereas results were mixed with adult samples. Youth were motivated to quit e-cigarettes by health concerns, whereas adults were motivated to quit e-cigarettes by cost, lack of satisfaction, and psychologic factors. Adults were more likely to report past e-cigarette quit attempts, most commonly "cold turkey." Few interventions tested strategies for e-cigarette cessation, with a majority targeted for youth. Given the lack of information on e-cigarette cessation, recommendations for future studies are outlined.
Project description:Coral disease has emerged over recent decades as a significant threat to coral reef ecosystems, with declines in coral cover and diversity of Caribbean reefs providing an example of the potential impacts of disease at regional scales. If similar trends are to be mitigated or avoided on reefs worldwide, a deeper understanding of the factors underlying the origin and spread of coral diseases and the steps that can be taken to prevent, control, or reduce their impacts is required. In recent years, an increased focus on coral microbiology and the application of classic culture techniques and emerging molecular technologies has revealed several coral pathogens that could serve as targets for novel coral disease diagnostic tools. The ability to detect and quantify microbial agents identified as indicators of coral disease will aid in the elucidation of disease causation and facilitate coral disease detection and diagnosis, pathogen monitoring in individuals and ecosystems, and identification of pathogen sources, vectors, and reservoirs. This information will advance the field of coral disease research and contribute knowledge necessary for effective coral reef management. This paper establishes the need for sensitive and specific molecular-based coral pathogen detection, outlines the emerging technologies that could serve as the basis of a new generation of coral disease diagnostic assays, and addresses the unique challenges inherent to the application of these techniques to environmentally derived coral samples.
Project description:IntroductionLeishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability and drug resistance as the occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties which have been used to treat bacterial and parasitic disease via various pathways especially as antimetabolites for folic acid.MethodsNew derivatives of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in brain heart infusion (BHI) medium and treated with varying concentrations of the new sulfonamide compounds. Light microscopy and viability tests were used to assess the cells with and without treatment.DiscussionA non-water soluble sulfonamide was determined to have 90-96% viability inhibition 24 hours after treatment with 100 µM final concentration. Because Leishmania are also autotrophs for folate precursors, the folic acid pathway was identified as a target for sulfonamide inhibition. When folic acid was added to untreated Leishmania, cell proliferation increased. A water soluble derivative of the inhibitory sulfonamide was synthesized and evaluated, resulting in less viability inhibition with a single dose (approximately 70% viability inhibition after 24 hours with 100 µM final concentration), but additive inhibition with multiple doses of the compound.ResultsHowever, the potential mechanism of inhibition was different between the water-soluble and non-water soluble sulfonamides. The inhibitory effects and potential pathways of inhibition indicate that these compounds may be new treatments for this disease.
Project description:Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.
Project description:Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. To ascertain the frequency of these issues in the literature, we performed a screen of 186 open-access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. An extension of this survey showed that these problems are not associated with journal or article level bibliometrics. Using seven independent RNA-seq datasets, we show misuse of enrichment tools alters results substantially. In conclusion, most published functional enrichment studies suffered from one or more major flaws, highlighting the need for stronger standards for enrichment analysis.
Project description:Approximately 1.5 million neonates receive general anesthesia each year for a surgical procedure. Despite this being an essential practice, a number of recent studies now indicate that anesthetic exposure could cause toxicity and neuronal apoptosis in the developing brain. This could potentially influence long-term neurodevelopmental outcome, especially premature infants in need of multiple surgical procedures. Most anesthetic drugs routinely administered to neonates have not been adequately tested for safety or efficacy. Given the number of confounders, dosing is often extrapolated from adults. This is concerning since many different drugs can be administered concurrently, with few of these agents actually approved for use by the Food and Drug Administration. Since 1997, legislation has been passed in the United States and abroad encouraging more drug investigation in infants and children. This has resulted in over 500 labeling changes to products regarding safety and efficacy in various pediatric age groups. However, only three drugs routinely used as anesthetic agents in newborn infants have had any updated labeling (none in very premature infants). This "off-label" use without adequate testing must be addressed. Therefore, more clinical trials of common anesthetic agents used alone and in combination in neonates are urgently needed.
Project description:Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.
Project description:Due to their superior tolerability and efficacy, β-lactams are the most potent and prescribed class of antibiotics in the clinic. The emergence of resistance to those antibiotics, mainly due to the production of bacterial enzymes called β-lactamases, has been partially solved by the introduction of β-lactamase inhibitors, which restore the activity of otherwise obsolete molecules. This solution is limited because currently available β-lactamase inhibitors only work against serine β-lactamases, whereas metallo-β-lactamases continue to spread, evolve, and confer resistance to all β-lactams, including carbapenems. Furthermore, the increased use of antibiotics to treat secondary bacterial pneumonia in severely sick patients with COVID-19 might exacerbate the problem of antimicrobial resistance. In this Personal View, we summarise the main advances accomplished in this area of research, emphasise the main challenges that need to be solved, and the importance of research on inhibitors for metallo-B-lactamases amidst the current pandemic.