Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.

Background: Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort.

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial.

Background: Alfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible for maintenance of cognition and neuroprotection by activation of brain pregnane X receptors and consequent increased production of mature brain-derived neurotrophic factor (m-BDNF). Two studies are reported here: an in vitro study investigated whether alfaxalone activates human pregnane X receptors (h-PXR) as effectively as allopregnanolone; and a clinical study that measured postoperative changes in serum m-BDNF and cognition in patients after alfaxalone anaesthesia compared with propofol and sevoflurane.

Hepatic Gene Expression Profiling of American Kestrels () Exposed In Ovo to Three Alternative Brominated Flame Retardants.

A number of brominated flame retardants (BFRs) have been reported to interfere with the thyroid signaling pathway and cause oxidative stress in birds, yet the underlying shifts in gene expression associated with these effects remain poorly understood. In this study, we measured hepatic transcriptional responses of 31 genes in American kestrel () hatchlings following in ovo exposure to one of three high-volume alternative BFRs: 1,2-bis(2,4,6-tribromophenoxy) ethane (BTPBE), bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), or 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB). Hatchling kestrels exhibited shifts in the expression of genes related to oxidative stress ( and ), thyroid hormone metabolism and transport (, and ), lipid and protein metabolism (PPAR, HMGCR, FAB1, and LPL), and cytokine-mediated inflammation ( and ).

Hematological and histological changes from ingestion of Deepwater Horizon crude oil in zebra finches (Taeniopygia guttata).

Exposure to crude oil during spill events causes a variety of pathologic effects in birds, including oxidative injury to erythrocytes, which is characterized in some species by the formation of Heinz bodies and subsequent anemia. However, not all species appear to develop Heinz bodies or anemia when exposed to oil, and there are limited controlled experiments that use both light and electron microscopy to evaluate structural changes within erythrocytes following oil exposure. In this study, we orally dosed zebra finches (Taeniopygia guttata) with 3.

Bold Behavior Is Associated with Genes That Regulate Energy Use but Does Not Covary with Body Condition in Food-Restricted Snails.

AbstractTheoretical models about the relationship between food restriction and individual differences in risk-taking behavior (i.e., boldness) have led to conflicting predictions: some models predict that food restriction increases boldness, while other models predict that food restriction decreases boldness.

Thyroid disruption and oxidative stress in American kestrels following embryonic exposure to the alternative flame retardants, EHTBB and TBPH.

Brominated flame retardant chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) (CAS #: 183658-27-7) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) (CAS #: 26040-51-7), have been detected in avian tissues and eggs from remote regions. Exposure to EHTBB and TBPH has been shown to cause oxidative stress and altered thyroid function in rodents and fish, yet no controlled studies have examined potential adverse effects of exposure in birds. Because flame retardants have been detected in wild raptors, we used American kestrels (Falco sparverius) as a model raptor to determine whether in ovo exposure to EHTBB or TBPH affected growth, hatching success, oxidative stress, or thyroid function.

Perception of infection: disease-related social cues influence immunity in songbirds.

While avoidance of sick conspecifics is common among animals, little is known about how detecting diseased conspecifics influences an organism's physiological state, despite its implications for disease transmission dynamics. The avian pathogen (MG) causes obvious visual signs of infection in domestic canaries (), including lethargy and conjunctivitis, making this system a useful tool for investigating how the perception of cues from sick individuals shapes immunity in healthy individuals. We tested whether disease-related social information can stimulate immune responses in canaries housed in visual contact with either healthy or MG-infected conspecifics.

Male zebra finches exposed to lead (Pb) during development have reduced volume of song nuclei, altered sexual traits, and received less attention from females as adults.

Lead (Pb) is a pervasive global contaminant that interferes with sensitive windows for neurological development and causes oxidative damage to tissues. The effects of moderate and high exposure to Pb have been well-studied in birds, but whether low-level early-life exposure to Pb influences adult phenotype remains unclear. Female songbirds use a male's song and coloration to discriminate between high- and low-quality males.

Weathered Mississippi Canyon 252 crude oil ingestion alters cytokine signaling, lowers heterophil:lymphocyte ratio, and induces sickness behavior in zebra finches (Taeniopygia guttata).

The Deepwater Horizon (DWH) oil spill caused an estimated 100,000 bird mortalities. However, mortality estimates are often based on the number of visibly oiled birds and likely underestimate the true damage to avian populations as they do not include toxic effects from crude oil ingestion. Elevated susceptibility to disease has been postulated to be a significant barrier to recovery for birds that have ingested crude oil.

Effects of sublethal application of Deepwater Horizon oil to bird eggs on embryonic heart and metabolic rate.

Following large crude oil spills, oil from feathers of brooding birds and oiled nesting material can transfer to eggs, resulting in reduced embryonic viability for heavily oiled eggs. Eggs may also be subjected to trace or light oiling, but functional teratogenic effects from sublethal crude oil exposure have not been examined. We assessed whether sublethal application of weathered Deepwater Horizon crude oil to the eggshell surface alters heart rate and metabolic rate in Zebra Finch (Taeniopygia guttata) embryos.

5-year longitudinal study of clinical and patient-reported outcomes in acute anterior uveitis.

Introduction: Acute anterior uveitis (AAU) is a frequently encountered form of uveitis, most commonly an immune-mediated condition associated with the HLA-B27 gene with or without spondyloarthritis, or idiopathic in nature. This study's aim was to measure clinical and patient-reported outcomes 5 years after the first episode of immune-mediated AAU.

Methods: This is a longitudinal observational study.

Fluorescent Heme Degradation Products Are Biomarkers of Oxidative Stress and Linked to Impaired Membrane Integrity in Avian Red Blood Cells.

Oxidative stress is generally understood to be an important mediator of life-history traits, yet the specific relationships between oxidative stress and life-history traits have been difficult to describe because there is often a lack of covariation among biomarkers of oxidative stress. For instance, although oxidative damage to red blood cell (RBC) membranes can lead to pathological conditions (i.e.

High-risk Corneal Transplantation: Recent Developments and Future Possibilities.

Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear.

Pharmacokinetic and Pharmacodynamic Analysis of Alfaxalone Administered as a Bolus Intravenous Injection of Phaxan in a Phase 1 Randomized Trial.

Background: Previous formulations of alfaxalone have shown it to be a fast-acting intravenous anesthetic with high therapeutic index. Alfaxalone has been reformulated for human use as Phaxan, an aqueous solution of 10 mg/mL of alfaxalone and 13% betadex. This study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of alfaxalone given as a bolus intravenous injection of this formulation to human male volunteers.

Bioenergetics-adverse outcome pathway: Linking organismal and suborganismal energetic endpoints to adverse outcomes.

Adverse outcome pathways (AOPs) link toxicity across levels of biological organization, and thereby facilitate the development of suborganismal responses predictive of whole-organism toxicity and provide the mechanistic information necessary for science-based extrapolation to population-level effects. Thus far AOPs have characterized various acute and chronic toxicity pathways; however, the potential for AOPs to explicitly characterize indirect, energy-mediated effects from toxicants has yet to be fully explored. Indeed, although exposure to contaminants can alter an organism's energy budget, energetic endpoints are rarely incorporated into ecological risk assessment because there is not an integrative framework for linking energetic effects to organismal endpoints relevant to risk assessment (e.

Development of the Pain-Related Beliefs and Attitudes about Sleep (PBAS) Scale for the Assessment and Treatment of Insomnia Comorbid with Chronic Pain.

Study Objectives: Dysfunctional beliefs and attitudes about sleep is a cognitive-behavioral factor central to the development and perpetuation of insomnia. Previous works to unravel the complex interrelationship between pain and insomnia have not explored the role of inflexible beliefs about the sleep-pain interaction, possibly due to a lack of a valid instrument for doing so. The current study evaluated the psychometric and functional properties of a 10-item Pain-Related Beliefs and Attitudes about Sleep (PBAS) scale.

Is altered behavior linked to cellular energy regulation in a freshwater mussel (Elliptio complanata) exposed to triclosan?

Environmental stress may alter the bioenergetic balance of organisms by resulting in greater energy investment into detoxification processes, which diverts energy from other biological functions. Here, we examine responses to triclosan (TCS) exposure in a freshwater mussel across multiple biological levels: behavioral (e.g.

A Phase 1c Trial Comparing the Efficacy and Safety of a New Aqueous Formulation of Alphaxalone with Propofol.

Background: Phaxan™ (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether β-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset-offset IV anesthetic like propofol, but causes less cardiovascular depression. This first-in-man study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation.

Long-Term Antihyperalgesic and Opioid-Sparing Effects of 5-Day Ketamine and Morphine Infusion ("Burst Ketamine") in Diabetic Neuropathic Rats.

Background: "Burst ketamine" (BK) is the long-term infusion of subanesthetic ketamine in combination with an opioid. It is used clinically with mixed success to provide long-term pain relief and improve opioid response in patients. BK has not been simulated preclinically, therefore, its effectiveness was investigated in an animal model of neuropathic pain--streptozotocin-induced diabetic neuropathy.

AMP-activated protein kinase is a biomarker of energetic status in freshwater mussels exposed to municipal effluents.

Although biomarkers are frequently used to assess sublethal effects of contaminants, a lack of mechanistic linkages to higher-level effects limits the predictive power of biomarkers. Bioenergetics has been proposed as a framework for linking cellular effects to whole-animal effects. We investigated sublethal effects of exposure to wastewater treatment facility effluent in freshwater mussels in situ, thereby capturing ecologically relevant exposure conditions.