Bait sprays - an alternative to control the European cherry fruit fly Rhagoletis cerasi ?

In 2005 initial experiments were carried out to control Rhagoletis cerasi with bait sprays. We used GF-120 fruit fly bait which contains Spinosad and NeemAzal®-T/S mixed in a sugar-yeast hydrolysate solution. 30 ml of bait sprays were applied on single cherry trees in field cages, where we released a defined number of cherry fruit flies. One experiment with GF-120 resulted in a reduction of fruit infestation of 96 % compared with the control. In other trials with GF-120 and Neem bait the effect on the cherry fruit fly population was monitored. After 24 hours GF-120 in a 5 % and 20 % solution led to a high reduction of flies (efficacy 85 %), whereas NeemAzal®-T/S in a 5 %, 10 %, and 20 % solution only resulted in efficacies between 34 % and 42 %. A significant effect of GF-120 was observed already after 3 hours

„Bait Sprays“ - eine Alternative zur Bekämpfung der Europäischen Kirschfruchtfliege Rhagoletis cerasi ?

In 2005 initial experiments were carried out to control Rhagoletis cerasi with bait sprays. We used GF-120 fruit fly bait which contains Spinosad and NeemAzal®-T/S mixed in a sugar-yeast hydrolysate solution. 30 ml of bait sprays were applied on single cherry trees in field cages, where we released a defined number of cherry fruit flies. One experiment with GF-120 resulted in a reduction of fruit infestation of 96 % compared with the control. In other trials with GF-120 and Neem bait the effect on the cherry fruit fly population was monitored. After 24 hours GF-120 in a 5 % and 20 % solution led to a high reduction of flies (efficacy 85 %), whereas NeemAzal®-T/S in a 5 %, 10 %, and 20 % solution only resulted in efficacies between 34 % and 42 %. A significant effect of GF-120 was observed already after 3 hours

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19

https://kent-islandora.s3.us-east-2.amazonaws.com/node/10701/11459-thumbnail.jpgAs we enter the second quarter of the COVID-19 pandemic, with testing for severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) increasingly available (though still limited and/or slow in some areas), we are faced with new questions and challenges regarding this novel virus. When to test? Whom to test? What to test? How often to test? And, what to do with test results? Since SARS–CoV-2 is a new virus, there is little evidence to fall back on for test utilization and diagnostic stewardship (1). Several points need to be considered to begin answering of these questions; specifically, what types of tests are available and under which circumstances are they useful? This understanding can help guide the use of testing at the local, regional, state, and national levels and inform those assessing the supply chain to ensure that needed testing is and continues to be available. Here, we explain the types of tests available and how they might be useful in the face of a rapidly changing and never-before-experienced situation. There are two broad categories of SARS–CoV-2 tests: those that detect the virus itself and those that detect the host’s response to the virus. Each will be considered separately. We must recognize that we are dealing with (i) a new virus, (ii) an unprecedented pandemic in modern times, and (iii) uncharted territory. With this in mind, in the absence of either proven effective therapy or a vaccine, diagnostic testing, which we have, becomes an especially important tool, informing patient management and potentially helping to save lives by limiting the spread of SARS–CoV-2. What is the most appropriate test, and for whom and when? Hypothetically, if the entire world’s population could be tested all at once, with a test providing 100% specificity and sensitivity (unrealistic, obviously), we might be able to identify all infected individuals and sort people into those who at that moment in time were asymptomatic, minimally/moderately symptomatic, and severely symptomatic. The asymptomatic and minimally/moderately symptomatic could be quarantined to avoid the spread of the virus, with the severely symptomatic managed and isolated in health care settings. Contract tracing could be carried out to find those at risk of being in the incubation period by virtue of their exposure. Alternatively, testing for a host response, if, again, the test were hypothetically 100% sensitive and specific, could identify those previously exposed to the virus and (if we knew this to be true, which we do not) label those who are immune to the virus, who could be tapped to work in settings where potentially infected individuals (e.g., sick patients in hospitals) might otherwise pose a risk. Unfortunately, these hypothetical scenarios are not reality. However, with this ideal situation as a guide, what we do have available as tests today should be carefully considered in terms of how they can be leveraged to move the current crisis closer to the ideal situation, especially in the absence of therapeutics or vaccines. Although the virus can be cultured, this is dangerous and not routinely done in clinical laboratories. While detection of viral antigens is theoretically possible, this approach has not, to date, been a primary one, but one that those participating in the summit considered to deserve further research.</p

Metabolically Stable Dibenzo[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)‑ones as Highly Selective p38 MAP Kinase Inhibitors: Optimizing Anti-Cytokine Activity in Human Whole Blood

Five series of metabolically stable disubstituted dibenzo­[<i>b</i>,<i>e</i>]­oxepin-11­(6<i>H</i>)-ones were synthesized and tested in a p38α enzyme assay for their inhibition of tumor necrosis factor-α (TNF-α) release in human whole blood. Compared to the monosubstituted dibenzo­[<i>b</i>,<i>e</i>]­oxepin-11­(6<i>H</i>)-one derivatives, it has been shown that the additional introduction of hydrophilic residues at position 9 leads to a substantial improvement of the inhibitory potency and metabolic stability. Using protein X-ray crystallography, the binding mode of the disubstituted dibenzoxepinones and the induction of a glyince flip in the hinge region were confirmed. The most potent compound of this series, <b>32e</b>, shows an outstanding biological activity on isolated p38α, with an IC₅₀ value of 1.6 nM, extraordinary selectivity (by a factor >1000, Kinase WholePanelProfiler), and low ATP competitiveness. The ability to inhibit the release of TNF-α from human whole blood was optimized down to an IC₅₀ value of 125 nM. With the promising dibenzoxepinone inhibitor <b>3i</b>, a pharmacokinetic study in mice was conducted

Considerations for the Terminal Sterilisation of Oligonucleotide Drug Products

A primary function of the parenteral drug product manufacturing process is to ensure sterility of the final product. The two most common methods for sterilizing parenteral drug products are terminal sterilisation (TS), whereby the drug product is sterilized in the final container following filling and finish, and membrane sterilisation, whereby the product stream is sterilized by membrane filtration and filled into pre-sterilized containers in an aseptic processing environment. Though TS provides greater sterility assurance than membrane sterilisation and aseptic processing, not all drug products are amenable to TS processes, which typically employ heat treatment or exposure to ionizing radiation. Oligonucleotides represent an emerging class of therapeutics that have great potential to treat a broad range of indications, including previously undruggable targets. Due to their size, structural complexity, and relative lack of governing regulations, there are several challenges in drug development that are unique for oligonucleotides. This exceptionality justifies a focused assessment of traditional chemistry, manufacturing, and control strategies prior to their adoption. In this article, we review the current state of sterile oligonucleotide drug product processing, highlight key aspects to consider when assessing options for product sterilisation, and provide recommendations to aid in the successful evaluation and development of TS processes. We also explore the current regulatory expectations and provide our interpretation as it pertains to oligonucleotide drug product