- The Evaluation of Inhalation Studies for Exposure Quality: A Case Study with Formaldehyde. [Journal Article]
- TLToxicol Lett 2019 May 13
- The inherent complexity of generating and monitoring a test article in an inhalation chamber can make inhalation toxicity testing challenging. Poor study design, human error, and electrical and mecha…
The inherent complexity of generating and monitoring a test article in an inhalation chamber can make inhalation toxicity testing challenging. Poor study design, human error, and electrical and mechanical problems can adversely affect an inhalation exposure and undermine a study's results. We have developed a process for evaluating seven key elements of exposure quality in inhalation chamber studies: 1) test article characterization, 2) generation method, 3) chamber sampling and analytical method, 4) chamber concentrations, 5) particle size characteristics, 6) chamber type, and 7) controls. For each study evaluated, exposure deficiencies are documented, and a study is given an overall rating (Robust, Adequate, or Poor) for the quality of its exposure characterization and documentation. In combination with the systematic consideration of experimental features other than exposure, these ratings can inform the utility of a study for use in hazard identification and/or exposure-response analysis. Exposure quality evaluations of 204 formaldehyde inhalation studies are presented as a case study. Of these, 34% were rated Robust because they had comprehensive exposure documentation and no serious deficiencies in the key elements of exposure quality. Another 19% of studies with minor uncertainties or limitations were rated Adequate. Conversely, 47% of the studies were rated Poor due to multiple serious exposure deficiencies. This formaldehyde case study illustrates the need to carefully consider the exposure quality of inhalation toxicity studies when their results are used to support hazard and risk assessments.
- Costs of isocyanate-related occupational diseases: A systematic review. [Journal Article]
- JOJ Occup Environ Hyg 2019 May 17; :1-21
- Although isocyanates are increasingly used in manufacturing and workplace exposure to isocyanates is widely recognized as one of the most frequent causes for occupational lung and skin diseases, litt…
Although isocyanates are increasingly used in manufacturing and workplace exposure to isocyanates is widely recognized as one of the most frequent causes for occupational lung and skin diseases, little is known about the economic burden on the affected individual and the society. This study provides an overview on costs of occupational diseases related to isocyanates. We performed a systematic literature search of studies in the electronic databases of the German Institute of Medical Documentation and Information, and the Canadian Centre for Occupational Health and Safety. We extracted the key characteristics of the studies and performed a study quality assessment. We identified eight studies on the costs of illness, of which five focused on occupational lung diseases and three on occupational skin diseases. Further, eight studies calculated loss of income/compensation payments. Out of the 16 identified articles, only two reported costs directly attributable to isocyanate-induced diseases (asthma). Studies were hardly comparable because they differed substantially in their methodological approaches. Moreover, the quality assessment of the studies revealed substantial limitations. While a wide range of isocyanate-related costs was identified, consequences of isocyanate-related occupational diseases were considerable in terms of societal costs and loss of income. In most studies, indirect costs were the main cost driver. There is a need for high-quality cost of illness studies on isocyanate-induced diseases stratified by degree of severity and sex. Such studies provide valuable information to develop preventive strategies and set priorities for measures to lower the burden of professional health risks.
- Novel PANK2 mutation discovered among South East Asian children living in Thailand affected with pantothenate kinase associated neurodegeneration. [Journal Article]
- JCJ Clin Neurosci 2019 May 11
- Pantothenate kinase-associated neurodegeneration (PKAN) is linked to brain iron accumulation caused by PANK2 gene mutation. Despite the importance of genetic testing to confirm PKAN and identify at r…
Pantothenate kinase-associated neurodegeneration (PKAN) is linked to brain iron accumulation caused by PANK2 gene mutation. Despite the importance of genetic testing to confirm PKAN and identify at risk parents, genetic screening is financially burdensome for developing countries like Thailand. Because genetic screeners are expensive and not reimbursed by the universal health care coverage system, they are not typically performed. To investigate clinical symptoms, radiological findings and mutation analysis for patients based in Thailand with unknown genetic status but suspected PKAN based on clinical symptoms. Genetic testing was performed for cases suspected for PKAN and their biological parents by direct genomic sequencing of PANK2 at Maharat Nakhon Ratchasima Hospital during 2017-2018. Clinical evaluation and documentation were performed by pediatric neurologists. Five children had classical onset form of PKAN. Most presented with gait dystonia. Three patients diagnosed after 4 years showed the eye-of-the-tiger sign in their brain MRI, whereas two younger patients revealed only isolated hyperintensity bilateral globus pallidus. However, PANK2 mutations were identified in all cases: the most common mutation was c.982-1G>C. This mutation was detected in four unrelated individuals but not reported in other studies. Genetic testing is recommended to confirm diagnoses in cases with supporting clinical features of PKAN with or without the classical 'eye-of-the-tiger-sign'. A novel PANK2 mutation (c.982-1G>C) was identified in South East Asian populations based in Thailand, suggesting that this genetic variant is a founder genotype in this population. Moreover, genetic diagnosis is helpful to provide appropriate genetic counseling to families.
- Physicochemical Stability of Compounded Naltrexone Hydrochloride Solutions in PCCA Base SuspendIt. [Journal Article]
- IJInt J Pharm Compd 2019 Mar-Apr; 23(2):157-162
- Naltrexone hydrochloride is an orally active narcotic antagonist used to facilitate rapid transition from methadone maintenance. The dosing schedule of naltrexone hydrochloride in detoxification prot…
Naltrexone hydrochloride is an orally active narcotic antagonist used to facilitate rapid transition from methadone maintenance. The dosing schedule of naltrexone hydrochloride in detoxification protocols needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of naltrexone hydrochloride currently exists. Naltrexone hydrochloride is commercially available as a scored, filmcoated, 50-mg tablet. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded naltrexone hydrochloride solutions in PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two naltrexone hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating HPLC assay for the determination of the chemical stability of naltrexone hydrochloride in SuspendIt was developed and validated. Solutions of naltrexone hydrochloride were prepared in SuspendIt at 0.5-mg/mL and 5.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic, amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and at the following time points: 7 days, 14 days, 29 days, 44 days, 61 days, 90 days, 120 days, and 180 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous preparation is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that naltrexone hydrochloride concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that naltrexone hydrochloride is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for naltrexone hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.
- Graduated colour tape measure: Development and demonstration of this tool in a case series of neonatal skin injuries. [Journal Article]
- JTJ Tissue Viability 2019 Apr 30
- CONCLUSIONS: A metric and colour tool can be used in conjunction with digital photographs to enhance objective assessment of neonatal skin injuries/wounds. The metric and colour tool provides the foundation for vital skin injury assessment and documentation essentials including injury bed colour, size and consideration of depth of damage.
- An extensive common-garden study with domesticated and wild Atlantic salmon in the wild reveals impact on smolt production and shifts in fitness traits. [Journal Article]
- EAEvol Appl 2019; 12(5):1001-1016
- Interactions between domesticated escapees and wild conspecifics represent a threat to the genetic integrity and fitness of native populations. For Atlantic salmon, the recurrent presence of large nu…
Interactions between domesticated escapees and wild conspecifics represent a threat to the genetic integrity and fitness of native populations. For Atlantic salmon, the recurrent presence of large numbers of domesticated escapees in the wild makes it necessary to better understand their impacts on native populations. We planted 254,400 eggs from 75 families of domesticated, F1-hybrid, and wild salmon in a river containing up- and downstream traps. Additionally, 41,630 hatchery smolts of the same pedigrees were released into the river. Over 8 years, 6,669 out-migrating smolts and 356 returning adults were recaptured and identified to their families of origin with DNA. In comparison with wild salmon, domesticated fish had substantially lower egg to smolt survival (1.8% vs. 3.8% across cohorts), they migrated earlier in the year (11.8 days earlier across years), but they only displayed marginally larger smolt sizes and marginally lower smolt ages. Upon return to freshwater, domesticated salmon were substantially larger at age than wild salmon (2.4 vs. 2.0, 4.8 vs. 3.2, and 8.5 vs. 5.6 kg across sexes for 1, 2, and 3 sea-winter fish) and displayed substantially lower released smolt to adult survival (0.41% vs. 0.94% across releases). Overall, egg-to-returning adult survival ratios were 1:0.76:0.30 and 1:0.44:0.21 for wild:F1-hybrid:domesticated salmon, respectively, using two different types of data. This study represents the most updated and extensive analysis of domesticated, hybrid, and wild salmon in the wild and provides the first documentation of a clear genetic difference in the timing of smolt migration-an adaptive trait presumed to be linked with optimal timing of entry to seawater. We conclude that spawning and hybridization of domesticated escapees can lead to (i) reduced wild smolt output and therefore wild adult abundance, through resource competition in freshwater, (ii) reduced total adult abundance due to freshwater competition and reduced marine survival of domesticated salmon, and (iii) maladaptive changes in phenotypic traits.
- Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea. [Journal Article]
- JHJ Hosp Infect 2019 May 08
- CONCLUSIONS: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients have multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.
- SPLATCHE3: simulation of serial genetic data under spatially explicit evolutionary scenarios including long-distance dispersal. [Journal Article]
- BBioinformatics 2019 May 11
- CONCLUSIONS: SPLATCHE3 simulates genetic data under a variety of spatially explicit evolutionary scenarios, extending previous versions of the framework. The new capabilities include long-distance migration, spatially and temporally heterogeneous short-scale migrations, alternative hybridization models, simulation of serial samples of genetic data and a large variety of DNA mutation models. These implementations have been applied independently to various studies, but grouped together in the current version.
- Integrated analysis of mRNA-seq and miRNA-seq in calyx abscission zone of Korla fragrant pear involved in calyx persistence. [Journal Article]
- BPBMC Plant Biol 2019 May 09; 19(1):192
- The objective of this study was to characterize molecular mechanism of calyx persistence in Korla fragrant pear by transcriptome and small RNA sequencing. Abscission zone tissues of flowers at three …
The objective of this study was to characterize molecular mechanism of calyx persistence in Korla fragrant pear by transcriptome and small RNA sequencing. Abscission zone tissues of flowers at three stages (the first, fifth and ninth days of the late bloom stage), with 50 mg/L GA3 (calyx persistence treatment, C_1, C_5, C_9) or 500 mg/L PP333 (calyx abscission treatment, T_1, T_5, T_9), were collected and simultaneously conducted transcriptome and small RNA sequencing.
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- Patient Participation During Anterior Cruciate Ligament Reconstruction Improves Comprehension, Satisfaction, and Functional Outcomes: A Simple Way to Improve Our Practices. [Journal Article]
- OJOrthop J Sports Med 2019; 7(4):2325967119841089
- CONCLUSIONS: Involving patients in their ACL reconstruction surgery improves their understanding of the procedure and their satisfaction with their care, which results in better outcomes at 1 year postoperatively.