Examining unused pharmaceuticals in the environment

Unused pharmaceuticals take an unhealthy toll on both the environment and human health. In the US alone, an estimated {dollar}1 billion of prescription drugs are thrown away each year. Increasing availability, marketing, and purchasing of both prescription and over-the-counter medications, coupled with the tendency of patients to discontinue use of and to stockpile drugs at home, is a unique problem that has garnered increasing attention among scientists, policymakers, and the media in the last ten years; These accumulated household drugs become unused pharmaceutical waste. This waste must be discarded and disposed of by the consumer. Historically, consumers have been instructed by health care professionals to dispose of unwanted medications into the sewage system. Inserts in some pharmaceutical packaging have also instructed consumer to flush expired and unused medications down the toilet. This method has historically also applied to pharmaceuticals stored in locations other than the consumer household; In the past decade studies have consistently identified amounts of pharmaceutical residues in water systems throughout the country. However, it has yet to be determined if the source of these substances found in the waterways is from excretion or disposal. While it is most likely a combination of both, it has been difficult to assess to what extent disposal takes place. Namely, there has been no source of data that would convey how often disposal takes place, what are the more common pharmaceutical compounds disposed, and in what quantities these compounds are flushed into our sewage systems; This dissertation describes a new methodology---compiling inventory data from coroner offices---which can provide a source of data detailing exactly how much of a specific pharmaceutical ingredient has been disposed in a particular geographic area and the frequency with which that compound is found in the disposal inventories. Further, this work assesses the many, varied, and often overlooked sites of accumulation of unused medications, the approximate relative contributions generated at each site, and common reasons why they accumulate in their respective locations. Finally, this work assesses the risk associated with inappropriate transfers of pharmaceuticals, and potential means for mitigating the risks

Skeletal pathology and variable anatomy in elephant feet assessed using computed tomography

Foot problems are a major cause of morbidity and mortality in elephants, but are underreported due to difficulties in diagnosis, particularly of conditions affecting the bones and internal structures. Here we evaluate post-mortem computer tomographic (CT) scans of 52 feet from 21 elephants (seven African Loxodonta africana and 14 Asian Elephas maximus), describing both pathology and variant anatomy (including the appearance of phalangeal and sesamoid bones) that could be mistaken for disease. We found all the elephants in our study to have pathology of some type in at least one foot. The most common pathological changes observed were bone remodelling, enthesopathy, osseous cyst-like lesions, and osteoarthritis, with soft tissue mineralisation, osteitis, infectious osteoarthriti, subluxation, fracture and enostoses observed less frequently. Most feet had multiple categories of pathological change (81% with two or more diagnoses, versus 10% with a single diagnosis, and 9% without significant pathology). Much of the pathological change was focused over the middle/lateral digits, which bear most weight and experience high peak pressures during walking. We found remodelling and osteoarthritis to be correlated with increasing age, more enthesopathy in Asian elephants, and more cyst-like lesions in females. We also observed multipartite, missing and misshapen phalanges as common and apparently incidental findings. The proximal (paired) sesamoids can appear fused or absent, and the predigits (radial/tibial sesamoids) can be variably ossified, though are significantly more ossified in Asian elephants. Our study reinforces the need for regular examination and radiography of elephant feet to monitor for pathology and as a tool for improving welfare

Medicines in Pharmacy Students’ Residence and Self-medication Practices

This study was aimed at identifying the types of medicines in pharmacy students’ residence and to determine if a relationship exists between keeping medicines in students’ accommodation and self-medication practices. A cross-sectional survey of a random sample of 240 undergraduate pharmacy students of the University of Jos, Jos, Nigeria, was carried out. Participating students were given a self-administered questionnaire, and only 188 students returned their filled questionnaire. The data collected were entered and analyzed using SPSS 16, and the χ2-test was used to determine associations between the variables. The results revealed that 66.0% of respondents had medicines in their room. A total of 318 medicines items (2.56 items per student's room) of which 37.1% were leftover medicines were present in respondents’ rooms. Analgesics (34.3%) and antibiotics (25.2%) were the common classes of medicines present in respondents’ rooms. Respondents reported getting these medicines on prescription (25.8%) and self-medication (56.5%) or both (17.7%). Self-medication practice was common among respondents (53.2%); however, no significant relationship (P>0.05) existed between having medicine in students’ room and self-medication practices. Common reasons given by respondents for having medicines in their rooms were that they were leftover medicines and that they were keeping them for emergency use or for use in an event of a similar illness. Most respondents (72.2%) reported disposing of their unused medicines in a trash can/dust bin. This study demonstrated that the prevalence of medicine storage in students’ room and self-medication practice is high. Analgesics and antibiotics were the most common types of medicines present in students’ residence

Lysosome-mediated processing of chromatin in senescence

Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression

PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.Peer reviewe

Pathology Case Study: Right Upper Anterior Thigh Lesion

This is a dermatologic case study presented by the University of Pittsburgh Department of Pathology in which a 26 year old female has a thigh lesion. Visitors are given both the microscopic and gross descriptions, including images, and are given the opportunity to diagnose the patient. This is an excellent resource for students in the health sciences to familiarize themselves with using laboratory results to diagnose. It is also a helpful site for educators to use to introduce or test student learning in dermatologic medicine