Monarch Butterfly Ecology, Behavior, and Vulnerabilities in North Central United States Agricultural Landscapes.

The North American monarch butterfly (Danaus plexippus) is a candidate species for listing under the Endangered Species Act. Multiple factors are associated with the decline in the eastern population, including the loss of breeding and foraging habitat and pesticide use. Establishing habitat in agricultural landscapes of the North Central region of the United States is critical to increasing reproduction during the summer. We integrated spatially explicit modeling with empirical movement ecology and pesticide toxicology studies to simulate population outcomes for different habitat establishment scenarios. Because of their mobility, we conclude that breeding monarchs in the North Central states should be resilient to pesticide use and habitat fragmentation. Consequently, we predict that adult monarch recruitment can be enhanced even if new habitat is established near pesticide-treated crop fields. Our research has improved the understanding of monarch population dynamics at the landscape scale by examining the interactions among monarch movement ecology, habitat fragmentation, and pesticide use.

Distribution and expression of type VI collagen and elastic fibers in human rotator cuff tendon tears.

There is increasing evidence for a progressive extracellular matrix change in rotator cuff disease progression. Directly surrounding the cell is the pericellular matrix, where assembly of matrix aggregates typically occurs making it critical in the response of tendon cells to pathological conditions. Studies in animal models have identified type VI collagen, fibrillin-1 and elastin to be located in the pericellular matrix of tendon and contribute in maintaining the structural and biomechanical integrity of tendon. However, there have been no reports on the localization of these proteins in human tendon biopsies. This study aimed to characterize the distribution of these ECM components in human rotator cuffs and gain greater insight into the relationship of pathology to tear size by analyzing the distribution and expression profiles of these ECM components. Confocal microscopy confirmed the localization of these structural molecules in the pericellular matrix of the human rotator cuff. Tendon degeneration led to an increased visibility of these components with a significant disorganization in the distribution of type VI collagen. At the genetic level, an increase in tear size was linked to an increased transcription of type VI collagen and fibrillin-1 with no significant alteration in the elastin levels. This is the first study to confirm the localization of type VI collagen, elastin and fibrillin-1 in the pericellular region of human supraspinatus tendon and assesses the effect of tendon degeneration on these structures, thus providing a useful insight into the composition of human rotator cuff tears which can be instrumental in predicting disease prognosis.

Elastic fibres are broadly distributed in tendon and highly localized around tenocytes.

Elastic fibres have the unique ability to withstand large deformations and are found in numerous tissues, but their organization and structure have not been well defined in tendon. The objective of this study was to characterize the organization of elastic fibres in tendon to understand their function. Immunohistochemistry was used to visualize elastic fibres in bovine flexor tendon with fibrillin-1, fibrillin-2 and elastin antibodies. Elastic fibres were broadly distributed throughout tendon, and highly localized longitudinally around groups of cells and transversely between collagen fascicles. The close interaction of elastic fibres and cells suggests that elastic fibres are part of the pericellular matrix and therefore affect the mechanical environment of tenocytes. Fibres present between fascicles are likely part of the endotenon sheath, which enhances sliding between adjacent collagen bundles. These results demonstrate that elastic fibres are highly localized in tendon and may play an important role in cellular function and contribute to the tissue mechanics of the endotenon sheath.

Conservation risks and benefits of establishing monarch butterfly (Danaus plexippus) breeding habitats close to maize and soybean fields in the north central United States: A landscape-scale analysis of the impact of foliar insecticide on nonmigratory monarch butterfly populations.

Establishing habitat in agricultural landscapes of the north central United States is critical to reversing the decline of North America's eastern monarch butterfly (Danaus plexippus) population. Insecticide use could create population sinks and threaten recovery. Discouraging habitat establishment within a 38-m zone around crop fields is a suggested risk mitigation measure. In Story County, Iowa, United States, this mitigation would discourage habitat establishment in 84% of roadsides and 38% of noncrop land. It is unclear if the conservation benefits from establishing habitat close to crop fields outweigh suppression of population growth owing to insecticide exposure. Consequently, monarch conservation plans require spatially and temporally explicit landscape-scale assessments. Using an agent-based model that incorporates female monarch movement and egg laying, the number and location of eggs laid in Story County were simulated for four habitat scenarios: current condition, maximum new establishment, moderate establishment, and moderate establishment only outside a 38-m no-plant zone around crop fields. A demographic model incorporated mortality from natural causes and insecticide exposure to simulate adult monarch production over 10 years. Assuming no insecticide exposure, simulated adult production increased 24.7% and 9.3%, respectively, with maximum and moderate habitat establishment and no planting restrictions. A 3.5% increase was simulated assuming moderate habitat establishment with a 38-m planting restriction. Impacts on adult production were simulated for six representative insecticides registered for soybean aphid (Aphis glycines) management. Depending on the frequency of insecticide applications over a 10-year period, simulated production increased 8.2%-9.3%, assuming moderate habitat establishment with no planting restrictions. Results suggest that the benefits of establishing habitat close to crop fields outweigh the adverse effects of insecticide spray drift; that is, metapopulation extirpation is not a concern for monarchs. These findings are only applicable to species that move at spatial scales greater than the scale of potential spray-drift impacts. Integr Environ Assess Manag 2021;17:989-1002. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Potential mortality effects of off-highway vehicles on the flat-tailed horned lizard (Phrynosoma mcallii): a manipulative experiment.

Southern California desert public lands receive especially high levels of off-highway recreation due to large population centers nearby and popular riding environments such as sand dunes. Controversy has developed over the flat-tailed horned lizard (Phrynosoma mcallii), previously a candidate for listing under the Endangered Species Act. Some evidence suggests lower lizard abundance in areas of higher recreational use than in areas with low or no use. We designed a manipulative experiment to ensure maximum inference in evaluating the direct impact of recreational riding of off-highway vehicles on lizards. Thirty-six lizards, in situ, were treated with an off-highway vehicle treatment during hibernation season in three treatment groups: high impact, low impact, and control. Treatments consisted of timed riding by off-highway vehicles. In all treatment groups survival was 100%, despite hibernation of lizards at very shallow depths. Consequently, indirect effects of off-highway vehicles deserve increased attention. The relative importance of direct versus indirect (i.e., degradation of lizard habitat) impacts caused by off-highway vehicles remains unknown. These indirect effects may include the altering of vegetation, substrate, and prey. We recommend that a manipulative approach be adopted to investigate these possibilities.

A pharmaceutical answer to nonadherence: Once weekly oral memantine for Alzheimer's disease.

Adherence to medication regimens is a major barrier to effective treatment in many disease areas, notably in dementia which causes cognitive impairment that reduces patients' awareness of non-adherence and their ability to manage medication. The development of oral dosage forms that can be infrequently dosed, and therefore improve adherence rate and facilitate direct observed therapy, has been a goal for decades. We describe the first demonstration of an oral formulation that achieves >7-day gastric retention and sustained pharmacokinetics in the challenging dog model. Gastric retention requires physical resistance of the dosage form to gastric emptying forces, which are known to be stronger in dogs than in humans, making successful gastric retention in dogs a stringent test for predicting human translatability. This formulation of memantine hydrochloride is the first oral dosage form that achieves multi-day drug release with near zero-order kinetics and efficient delivery. In the dog model, relative memantine bioavailability approaches 100% with sustained plasma levels of memantine over seven days and profiles that can be tuned by varying components of the formulation. A single gastric resident dosage form achieves an AUC equivalent to 7 daily treatments with the marketed daily capsule, with a Cmax that is no higher than the daily product. PK modeling predicts that the gastroretentive formulation will maintain therapeutic blood levels in humans when administered once weekly. The formulation methodology presented here is applicable to many water soluble drugs and may enable the development of long-acting oral therapies for a wide variety of conditions.

Patients' and Care Providers' Perceptions of Television-Based Education in the Intensive Care Unit.

BACKGROUND: Delivery of patient education materials to promote health literacy is a vital component of patient-centered care, which improves patients' decision-making, reduces patients' anxiety, and improves clinical outcomes. OBJECTIVES: To evaluate perceptions of television-based patient education among patients, caregivers, nurses, and other care providers (attending physicians, advanced practice nurses, physician assistants, and resident fellows) in the intensive care unit. METHODS: A Likert-scale survey of the perceptions of patients, caregivers, nurses, and other care providers in the medical and cardiovascular intensive care units of a large academic medical center. Perceptions of the effects of television-based education on anxiety, knowledge, and health-related decision-making were assessed. RESULTS: A total of 188 participants completed the survey. Among them, 75% of nurses and 76% of other providers agreed or strongly agreed that television-based education improved patients' and caregivers' knowledge (P = .95). More nurses (47%) than other providers (29%) agreed that television-based education would lead to more informed health decisions by patients (P = .04). Patients and caregivers are 23 times more likely than providers to strongly agree that television-based education reduces anxiety, and they are more optimistic regarding the benefits of television-based education (relative risk ratio 23.47; 95% CI 9.75-56.45; P < .001). CONCLUSION: Patients and caregivers strongly suggested that television is a useful tool for providing health literacy education in an intensive care unit.

A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.

Changing the pill: developments toward the promise of an ultra-long-acting gastroretentive dosage form.

INTRODUCTION: The development of oral sustained release dosage forms has been a longstanding goal due to the potential for ease of administration, improved pharmacokinetics, reduced dosing frequency, and improved adherence. The benefits of multiday single-dose drug delivery are evident in the success and patient adoption of injected and implanted dosage forms. However, in the space of oral medications, all current commercially available gastric resident dosage forms, and most in development, are limited to gastric residence of less than 1 day. AREAS COVERED: Reviews of systems to extend gastric residence reveal that 1 day or more residence has been an unmet challenge. New dosage forms are in development that seek to address many of the key physiological and design challenges of long-term gastric retention beyond 24 h  and up to a week or longer. The present analysis highlights the design, material considerations and implications of unfolding dosage form systems with ultra-long-term gastric residence. EXPERT OPINION: The development of oral dosage forms providing sustained release of high potency medications over days or weeks could transform care, significantly decrease patient burden in chronic disease management and improve outcomes.

Caffeine-catalyzed gels.

Covalently cross-linked gels are utilized in a broad range of biomedical applications though their synthesis often compromises easy implementation. Cross-linking reactions commonly utilize catalysts or conditions that can damage biologics and sensitive compounds, producing materials that require extensive post processing to achieve acceptable biocompatibility. As an alternative, we report a batch synthesis platform to produce covalently cross-linked materials appropriate for direct biomedical application enabled by green chemistry and commonly available food grade ingredients. Using caffeine, a mild base, to catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized monomers with citric acid as a tri-functional crosslinking agent we introduce a novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical properties, which can be tailored in shape, surface texture, solvent response, cargo release, shear and tensile strength, among other potential attributes. The demonstrated versatility, low cost and facile synthesis of these CCGs renders them appropriate for a broad range of customized engineering applications including drug delivery constructs, tissue engineering scaffolds, and medical devices.

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals.

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

The Mechanical, Structural, and Compositional Changes of Tendon Exposed to Elastase.

The mechanical response of tendon is dependent on the interaction of structural molecules that constitute the extracellular matrix. However, little is known about the role of elastic fibers that are present in this structure. Elastase treatments have been used to elucidate the mechanical role of elastic fibers in numerous tissues. Here, we show that a standard elastase treatment affects the mechanical properties of tendon, including the ultimate tensile strength and failure strain. Moreover, elastase-treated specimens exhibit significant structural and compositional changes including crimp undulation and release of glycosaminoglycans. These data demonstrate that a common elastase treatment has a complex digestion profile that influences the structure-function relationship of tendon. Thus, defining the mechanical role of elastic fibers in tendon using this technique is challenging. This introduces new and exciting questions regarding the function of elastic fibers in tendon, which may not be as well understood as previously thought.

Clubbing masculinities: gender shifts in gay men's dance floor choreographies.

This article adopts an interdisciplinary approach to understanding the intersections of gender, sexuality, and dance. It examines the expressions of sexuality among gay males through culturally popular forms of club dancing. Drawing on political and musical history, I outline an account of how gay men's gendered choreographies changed throughout the 1970s, 80s, and 90s. Through a notion of "technologies of the body," I situate these developments in relation to cultural levels of homophobia, exploring how masculine expressions are entangled with and regulated by musical structures. My driving hypothesis is that as perceptions of cultural homophobia decrease, popular choreographies of gay men's dance have become more feminine in expression. Exploring this idea in the context of the first decade of the new millennium, I present a case study of TigerHeat, one of the largest weekly gay dance club events in the United States.