Effect of temperature, age and lifespan extending interventions on Caenorhabditis elegans models of amyloid beta pathology

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that accounts for 60-70% of all dementia cases worldwide. The hallmark of AD is neuronal death precipitated by accrual of intercellular amyloid (Aβ) aggregates and intracellular neurofibrillary (NFT) Tau tangles. AD risk factors include age, genetics and environment. Despite intense research, the genetic and biochemical underpinnings of AD are poorly understood, and no drugs have been discovered for curing the disease. In this project, we aimed to study the impact of temperature, age and longevity-promoting interventions on two Caenorhabditis elegans transgenic strains modeling aspects of Aβ pathophysiology, by expressing full length human (1-42 amino acids) Aβ peptide in muscles or neurons. Since AD is an age-related disease, we first examined how age influenced the dynamics of Aβ-mediated phenotypes, followed by the impact of an additional stress modality- high temperature. As previously reported, worms expressing Aβ in muscles exhibited full body paralysis and mobility defects at high temperatures of 25 °C. Contrarily, the animals expressing Aβ in neurons did not show any paralysis but underwent distinct mobility defects under temperature stress. Surprisingly, we discovered that in both models the extent of pathology was only moderately aggravated by increasing age alone, or upon combining age and temperature stressors. Since aging is the biggest risk factor for AD, we also asked if genetic or chemical interventions known to increase lifespan could impact the phenotypes of the worm Aβ models. We found that a known lifespan-extending drug, promethazine•HCl, significantly delayed the onset of paralysis and mobility defects in the Aβ (muscle) model on day 1 of the animal. Similarly, we found that two known lifespan extending transcription factors, DAF-16 and NHR-49, also played an important role in alleviating Aβ phenotypes on day 1 and influenced the ability of promethazine•HCl to retard Aβ pathology. Overall, in characterizing an in vivo worm platform for identifying drugs and genes that impact AD, we have delineated the interlinked effects of age, temperature and genetic environment on Aβ pathology

Intermittent exotropia: Surgical treatment strategies

Surgical management of intermittent exotropias (IXTs) is ambiguous, with techniques of management varying widely between institutions. This review aims to examine available literature on the surgical management of IXT. A literature search was performed using PubMed, Web of Knowledge, LILACS, and the University of Liverpool Orthoptic Journals and Conference Transactions Database. All English-language papers published between 1958 and the present day were considered