Current pharmacotherapeutic strategies for Strongyloidiasis and the complications in its treatment

Introduction: Strongyloidiasis, an infection caused by the soil-transmitted helminth Strongyloides stercoralis, can lead immunocompromised people to a life-threatening syndrome. We highlight here current and emerging pharmacotherapeutic strategies for strongyloidiasis and discuss treatment protocols according to patient cohort. We searched PubMed and Embase for papers published on this topic between 1990 and May 2022. Areas covered: Ivermectin is the first-line drug, with an estimated efficacy of about 86% and excellent tolerability. Albendazole has a lower efficacy, with usage advised when ivermectin is not available or not recommended. Moxidectin might be a valid alternative to ivermectin, with the advantage of being a dose-independent formulation. Expert opinion: The standard dose of ivermectin is 200 mu g/kg single dose orally, but multiple doses might be needed in immunosuppressed patients. In the case of hyperinfection, repeated doses are recommended up to 2 weeks after clearance of larvae from biological fluids, with close monitoring and further dosing based on review. Subcutaneous ivermectin is used where there is impaired intestinal absorption/paralytic ileus. In pregnant or lactating women, studies have not identified increased risk with ivermectin use. However, with limited available data, a risk-benefit assessment should be considered for each case

Reexamining Chronic \u3cem\u3eToxoplasma gondii\u3c/em\u3e Infection: Surprising Activity for a Dormant Parasite

Purpose of Review Despite over a third of the world’s population being chronically infected with Toxoplasma gondii, little is known about this largely asymptomatic phase of infection. This stage is mediated in vivo by bradyzoites within tissue cysts. The absence of overt symptoms has been attributed to the dormancy of bradyzoites. In this review, we reexamine the conventional view of chronic toxoplasmosis in light of emerging evidence challenging both the nature of dormancy and the consequences of infection in the CNS. Recent Findings New and emerging data reveal a previously unrecognized level of physiological and replicative capacity of bradyzoites within tissue cysts. These findings have emerged in the context of a reexamination of the chronic infection in the brain that correlates with changes in neuronal architecture, neurochemistry, and behavior that suggest that the chronic infection is not without consequence. Summary The emerging data driven by the development of new approaches to study the progression of chronic toxoplasma infection reveals significant physiological and replicative capacity for what has been viewed as a dormant state. The emergence of bradyzoite and tissue cyst biology from what was viewed as a physiological “black box” offers exciting new areas for investigation with direct implications on the approaches to drug development targeting this drug-refractory state. In addition, new insights from studies on the neurobiology on chronic infection reveal a complex and dynamic interplay between the parasite, brain microenvironment, and the immune response that results in the detente that promotes the life-long persistence of the parasite in the host

Forest conservation delivers highly variable coral reef conservation outcomes

Coral reefs are threatened by human activities on both the land (e.g., deforestation) and the sea (e.g., overfishing). Most conservation planning for coral reefs focuses on removing threats in the sea, neglecting management actions on the land. A more integrated approach to coral reef conservation, inclusive of land–sea connections, requires an understanding of how and where terrestrial conservation actions influence reefs. We address this by developing a land–sea planning approach to inform fine-scale spatial management decisions and test it in Fiji. Our aim is to determine where the protection of forest can deliver the greatest return on investment for coral reef ecosystems. To assess the benefits of conservation to coral reefs, we estimate their relative condition as influenced by watershed-based pollution and fishing. We calculate the cost-effectiveness of protecting forest and find that investments deliver rapidly diminishing returns for improvements to relative reef condition. For example, protecting 2% of forest in one area is almost 500 times more beneficial than protecting 2% in another area, making prioritization essential. For the scenarios evaluated, relative coral reef condition could be improved by 8–58% if all remnant forest in Fiji were protected rather than deforested. Finally, we determine the priority of each coral reef for implementing a marine protected area when all remnant forest is protected for conservation. The general results will support decisions made by the Fiji Protected Area Committee as they establish a national protected area network that aims to protect 20% of the land and 30% of the inshore waters by 2020. Although challenges remain, we can inform conservation decisions around the globe by tackling the complex issues relevant to integrated land–sea planning

Endogenous networks and international cooperation

The rise of social network analyses in the social sciences has allowed empirical work to better account for interdependencies among actors and among their actions. However, this work has been, to a large extent, descriptive: it has treated these actions as exogenous and immutable. In many cases these networks describe actions like alliance formation or trade phenomena that are the outcome variables for programs of social scientific research. In this paper, I attempt to account for both interdependencies and the endogenous nature of networks by incorporating formal theory; helping answer the question of how these networks arise by looking at the incentives of actors to form links with each other. I discuss the appropriate solution concept for a network formation game, and present an algorithm for finding the equilibrium of these networks computationally as well as ways to compare the theoretical networks to observed ones in order to evaluate the fit of the theory. I apply these methods to the study of international cooperation a subject where both the interdependencies and purposive nature of actors must be accounted for. The theoretical network is able to reproduce a number of important observed characteristics. Still, there are more factors that must be accounted for if we want to understand how the network of international cooperation is formed

Bottom pressure torque and the vorticity balance from observations in Drake Passage

The vorticity balance of the Antarctic Circumpolar Current in Drake Passage is examined using 4 years of observations from current‐ and pressure‐recording inverted echo sounders. The time‐varying vorticity, planetary and relative vorticity advection, and bottom pressure torque are calculated in a two‐dimensional array in the eddy‐rich Polar Frontal Zone (PFZ). Bottom pressure torque is also estimated at sites across Drake Passage. Mean and eddy nonlinear relative vorticity advection terms dominate over linear advection in the local (50‐km scale) vorticity budget in the PFZ, and are balanced to first order by the divergence of horizontal velocity. Most of this divergence comes from the ageostrophic gradient flow, which also provides a second‐order adjustment to the geostrophic relative vorticity advection. Bottom pressure torque is approximately one‐third the size of the local depth‐integrated divergence. Although the cDrake velocity fields exhibit significant turning with depth throughout Drake Passage even in the mean, surface vorticity advection provides a reasonable representation of the depth‐integrated vorticity balance. Observed near‐bottom currents are strongly topographically steered, and bottom pressure torques grow large where strong near‐bottom flows cross steep topography at small angles. Upslope flow over the northern continental slope dominates the bottom pressure torque in cDrake, and the mean across this Drake Passage transect, 3 to urn:x-wiley:21699275:media:jgrc21771:jgrc21771-math-0001 m s−2, exceeds the mean wind stress curl by a factor of 15–20

Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing

RNA-based drugs depend on chemical modifications to increase potency and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. Here, we explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor. We identify several heavily modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2\u27-OH groups) that are functional in human cells. These designs will contribute to Cas9-based therapeutics since heavily modified RNAs tend to be more stable in vivo (thus increasing potency). We anticipate that our designs will improve the use of Cas9 via RNP and mRNA delivery for in vivo and ex vivo purposes