Current Advancements in Mouse Models of Retinal Disease.

The field of retinal degenerative (RDs) disease study has been in a state of exponential growth from discovering the underlying genetic components of such diseases as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) to the first gene therapy developed and approved for human Leber congenital amaurosis. However, a source for high-fidelity animal models of these complex, multifactorial, and/or polygenic diseases is a need that has yet to be fulfilled. While models for AMD and RP do exist, they often require aging the animals for a year or more, feeding special diets, or introduction of external modulators such as exposure to cigarette smoke. Currently, work is being done to uncover high-fidelity naturally occurring models of these retinal diseases with the hope and intent of providing the vision community the tools it needs to better understand, treat, and, one day, cure the patients suffering from these devastating afflictions.

Anthropogenic changes in sodium affect neural and muscle development in butterflies.

The development of organisms is changing drastically because of anthropogenic changes in once-limited nutrients. Although the importance of changing macronutrients, such as nitrogen and phosphorus, is well-established, it is less clear how anthropogenic changes in micronutrients will affect organismal development, potentially changing dynamics of selection. We use butterflies as a study system to test whether changes in sodium availability due to road salt runoff have significant effects on the development of sodium-limited traits, such as neural and muscle tissue. We first document how road salt runoff can elevate sodium concentrations in the tissue of some plant groups by 1.5-30 times. Using monarch butterflies reared on roadside- and prairie-collected milkweed, we then show that road salt runoff can result in increased muscle mass (in males) and neural investment (in females). Finally, we use an artificial diet manipulation in cabbage white butterflies to show that variation in sodium chloride per se positively affects male flight muscle and female brain size. Variation in sodium not only has different effects depending on sex, but also can have opposing effects on the same tissue: across both species, males increase investment in flight muscle with increasing sodium, whereas females show the opposite pattern. Taken together, our results show that anthropogenic changes in sodium availability can affect the development of traits in roadside-feeding herbivores. This research suggests that changing micronutrient availability could alter selection on foraging behavior for some roadside-developing invertebrates.

Nutrition shapes life-history evolution across species.

Nutrition is a key component of life-history theory, yet we know little about how diet quality shapes life-history evolution across species. Here, we test whether quantitative measures of nutrition are linked to life-history evolution across 96 species of butterflies representing over 50 independent diet shifts. We find that butterflies feeding on high nitrogen host plants as larvae are more fecund, but their eggs are smaller relative to their body size. Nitrogen and sodium content of host plants are also both positively related to eye size. Some of these relationships show pronounced lineage-specific effects. Testis size is not related to nutrition. Additionally, the evolutionary timing of diet shifts is not important, suggesting that nutrition affects life histories regardless of the length of time a species has been adapting to its diet. Our results suggest that, at least for some lineages, species with higher nutrient diets can invest in a range of fitness-related traits like fecundity and eye size while allocating less to each egg as offspring have access to a richer diet. These results have important implications for the evolution of life histories in the face of anthropogenic changes in nutrient availability.

The Well-Defined Pediatric ICU: Active Surveillance Using Nonmedical Personnel to Capture Less Serious Safety Events.

BACKGROUND: Adverse events, diverse and often costly, commonly occur in pediatric intensive care units (PICUs). Serious safety events (SSEs) are captured through well-developed systems, typically by voluntary reporting. Less serious safety events (LSSEs), including close calls, however, occur at a higher frequency than those that result in immediate harm or death but are underestimated by standard reporting systems. LSSEs can reveal system defects and precede serious events resulting in patient or provider harm. METHODS: A unique active surveillance program was created at Children's Hospitals and Clinics of Minnesota to quantify and categorize, and, ultimately reduce, LSSEs, in PICUs. Premedical college graduates without formal health care training daily canvassed the PICUs and facilitated reporting of LSSEs at the point of care. Events were recorded on a Web application and stored in a relational database management system. Events were enumerated and categorized according to distinctive characteristics (Theme Index) and real or potential harm (Harm Index). RESULTS: Some 1,980 PICU patients, representing 10,766 PICU patient-days in a 15-month period (June 1, 2013- August 31, 2014) experienced 2,465 LSSEs-5.4 LSSEs/ day or 0.23 LSSEs/patient-day. Such events resulted in a patient intervention 38% of the time. Some 158 quality/safety improvement projects were initiated during the observation period, 74 of which have been completed. Quality/safety information was broadcasted to providers, local leadership, and hospital management. CONCLUSIONS: LSSEs occur frequently in our PICUs. Non-health care providers can cost-effectively facilitate reporting by actively canvassing PICU providers on a daily basis and can contribute to quality/safety improvement projects and local safety culture. Reported events can serve as a focus for quality/safety improvement projects. A Web application and mobile tablet interfaces are efficient tools to record events.

Evaluation of Pregabalin bioadhesive multilayered microemulsion IOP-lowering eye drops.

In spite of available treatment options, glaucoma continues to be a leading cause of irreversible blindness in the world. Current glaucoma medications have multiple limitations including: lack of sustained action; requirement for multiple dosing per day, ocular irritation and limited options for drugs with different mechanisms of action. Previously, we demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. The current study was designed to evaluate pregabalin microemulsion eye drops and to estimate its efficacy in humans using in silico methods. Molecular docking studies of pregabalin against CACNA2D1 of mouse, rabbit, and human were performed. Pregabalin microemulsion eye drops were characterized using multiple in vivo studies and its stability was evaluated over one year at different storage conditions. Molecular docking analyses and QSPR of pregabalin confirmed its suitability as a new IOP-lowering medication that functions using a new mechanism of action by binding to CACNA2D1 in all species evaluated. Because of its prolonged corneal residence time and corneal penetration enhancement, a single topical application of pregabalin ME can provide an extended IOP reduction of more than day in different animal models. Repeated daily dosing for 2 months confirms the lack of any tachyphylactic effect, which is a common drawback among marketed IOP-lowering medications. In addition, pregabalin microemulsion demonstrated good physical stability for one year, and chemical stability for 3-6 months if stored below 25 °C. Collectively, these outcomes greatly support the use of pregabalin eye drops as once daily IOP-lowering therapy for glaucoma management.

The relationship between arterial carbon dioxide tension and end-tidal carbon dioxide tension in intubated adults with traumatic brain injuries who required emergency craniotomies.

Anesthetic management of patients who have suffered traumatic brain injuries can be challenging. We investigated the relationship between arterial to end-tidal carbon dioxide partial pressure gradients (Pa-etCO2) and 3 predictor variables: (1) injury severity score, (2) use of positive end-expiratory pressure, and (3) presence of rib fractures. Using a convenient sampling method, we sampled 56 patients who arrived to the operating room intubated after traumatic brain injuries between 2005 and 2011. Two groups were compared retrospectively: those with Pa-etCO2 greater than 10 mm Hg (case group) (n = 37) and those with Pa-etCO2 gradients of 10 mm Hg or less (control group) (n = 19). Descriptive and inferential statistics were employed to identify any differences between the groups. Stepwise regression was also performed. Cross tabulation analysis revealed that injury severity score of 30 or more was a predictor of Pa-etCO2 gradient. Stepwise regression analysis revealed the presence of rib fracture and body mass index to be significant predictors of Pa-etCO2 gradient (P < .011). This study identified coexisting conditions in which the patients' Pa-etCO2 gradients were large. Results showed that injury severity score of 30 or more, the presence of rib fractures, and higher body mass index were statistically significant predictors of Pa-etCO2 gradients greater than 10 mm Hg. These observations should be considered when evaluating PetCO2 in conjunction with arterial blood gas analysis to determine optimal ventilation status of these patients.

Difficult airway management following severe gasoline burn injury: a case report.

Airway management following severe gasoline burn injury can be difficult. Because patients with severe burns may be treated at a variety of hospitals that provide emergent care, it is valuable for Certified Registered Nurse Anesthetists who work in such facilities to have an understanding of the care of these patients. Airway management is an extremely important consideration in the care of burn victims. If not done in a timely manner, lethal complications may result. This article reports the experience of caring for a female who was involved in an altercation, doused with gasoline, and set on fire. Consequently, airway obstruction developed and progressively worsened. Airway management interventions began with bag-valve-mask-assisted ventilation and progressed through orotracheal intubation attempts, attempts to insert a laryngeal mask airway, cricothyrotomy, emergency tracheostomy, and surgical tracheostomy.

Effects of topical lidocaine on successful extubation time among patients undergoing elective carotid endarterectomies.

Little research has been done on the effects that topical intratracheal anesthesia have on the length of time required to successfully extubate patients after surgical interventions. This retrospective case-control study, using a convenience sample (n = 100 patients), explored the effects of using topical lidocaine laryngotracheal anesthesia injected into the adult trachea before insertion of the endotracheal tube on patients undergoing surgical treatment for blockage of the carotid artery. Both descriptive and inferential analyses were performed to evaluate differences among all variables. Multiple linear regression was also performed while adjusting for the confounding factors (age, gender, and smoking status). Results revealed that the use of lidocaine laryngotracheal anesthesia during induction of anesthesia prolonged the mean times for postoperative removal of the endotracheal tube by nearly 2 minutes. Extended time for removal of endotracheal tubes may lead to increased costs to the healthcare institution and to the patient, which in turn may lead to dissatisfaction within healthcare teams and possibly to patient discontent with care provided.

Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration in a Spontaneous Polygenic Model of Inherited Retinal Dystrophy.

Collectively, retinal neurodegenerative diseases are comprised of numerous subtypes of disorders which result in loss of a varying cell types in the retina. These diseases can range from glaucoma, which results in retinal ganglion cell death, to age-related macular degeneration and retinitis pigmentosa, which result in cell death of the retinal pigment epithelium, photoreceptors, or both. Regardless of the disease, it's been recently found that increased release of proinflammatory cytokines and proliferation of active microglia result in a remarkably proinflammatory microenvironment that assists in the pathogenesis of the disease; however, many of the details of these inflammatory events have yet to be elucidated. In an ongoing study, we have used systems genetics to identify possible models of spontaneous polygenic age-related macular degeneration by mining the BXD family of mice using single nucleotide polymorphism analyses of known genes associated with the human retinal disease. One BXD strain (BXD32) was removed from the study as the rate of degeneration observed in these animals was markedly increased with a resultant loss of most all photoreceptors by 6 months of age. Using functional and anatomical exams including optokinetic nystamography, funduscopy, fluorescein angiography, and optical coherence tomography, along with immunohistochemical analyses, we show that the BXD32 mouse strain exhibits a severe neurodegenerative phenotype accompanied by adverse effects on the retinal vasculature. We also expose the concurrent establishment of a chronic proinflammatory microenvironment including the TNFα secretion and activation of the NF-κB and JAK/STAT pathways with an associated increase in activated macrophages and phagoptosis. We conclude that the induced neuronal death and proinflammatory pathways work synergistically in the disease pathogenesis to enhance the rate of degeneration in this spontaneous polygenic model of inherited retinal dystrophy.

Tracking Red Palm Mite Damage in the Western Hemisphere Invasion with Landsat Remote Sensing Data.

Red palm mites (Raoiella indica Hirst, Acari: Tenuipalpidae) were first observed in the western hemisphere on the islands and countries surrounding the Caribbean Sea, infesting the coconut palm (Cocos nucifera L.). Detection of invasive pests usually relies upon changes in vegetation properties as result of the pest activity. These changes may be visible in time series of satellite data records, such as Landsat satellites, which have been available with a 16-day repeat cycle at a spatial resolution of 30 m since 1982. Typical red palm mite infestations result in the yellowing of the lower leaves of the palm crown; remote sensing model simulations have indicated that this feature may be better detected using the green normalized difference vegetation index (GNDVI). Using the Google Earth Engine programming environment, a time series of Landsat 5 Thematic Mapper, Landsat 7 Enhanced Thematic Mapper Plus and Landsat 8 Operational Land Imager data was generated for plantations in northern and northeast Brazil, El Salvador, and Trinidad-Tobago. Considering the available studied plantations, there were little or no differences of GNDVI before and after the dates when red palm mites were first revealed at each location. A discussion of possible alternative approaches are discussed related to the limitations of the current satellite platforms.

An erosive lesion in the orbital apex as the presenting sign of sarcoidosis.

Sarcoidosis is an autoimmune granulomatous disease that can affect any organ system in the body. Ocular and orbital manifestations are relatively common. Osseous involvement is rare and usually involves bones of the appendicular skeleton. We present an unusual case of an erosive sarcoid granuloma in a 48-year-old woman that involved the orbital apex. This case highlights diagnosis, treatment, and the importance of full systemic workup to determine the extent of the disease.

Continuous subcutaneous insulin infusion during general anesthesia: a case report.

Care of the patient with diabetes mellitus presents numerous challenges to the anesthesia practitioner. There is no perfect way to care for these patients nor are any 2 patients with diabetes exactly alike. With the advent of subcutaneous insulin pumps, the anesthesia practitioner has another tool to assist him or her in giving high quality care. This case study describes the anesthesia care provided to a patient with type 1 diabetes who wore his continuous subcutaneous insulin infusion (CSII) pump during general anesthesia for surgical repair of a herniated lumbar disk. Importantly, the anesthesia plan involved a collaborative effort with the patient. Blood glucose levels were stable throughout the perioperative period. Little or no extra work was required of the CRNA. This case showed that the CSII could be used to minimize perioperative fluctuations in blood sugar. Postoperatively, the patient expressed a high degree of satisfaction with the anesthetic.

Incorporating natural capital into economy-wide impact analysis: a case study from Alberta.

Traditionally, decision-makers have relied on economic impact estimates derived from conventional economy-wide models. Conventional models lack the environmental linkages necessary for examining environmental stewardship and economic sustainability, and in particular the ability to assess the impact of policies on natural capital. This study investigates environmentally extended economic impact estimation on a regional scale using a case study region in the province of Alberta known as the Foothills Model Forest (FMF). Conventional economic impact models are environmentally extended in pursuit of enhancing policy analysis and local decision-making. It is found that the flexibility of the computable general equilibrium (CGE) modeling approach offers potential for environmental extension, with a solid grounding in economic theory. The CGE approach may be the tool of the future for more complete integrated environment and economic impact assessment.