Browsing by Author "Hughes, Claude"

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Open Access
10.29011/2576-9596. 100035
(Sports Injuries & Medicine) Hughes, Claude
Open Access
A caution in association of ABO blood group with COVID-19
(Global Clinical and Translational Research, 2020-06-10) Hughes, Claude; Zhang, Fengyu
Open Access
An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment.
(Environmental health perspectives, 2005-08) vom Saal, Frederick S; Hughes, Claude
Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 microg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10(-12) M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice; and d) recent epidemiologic evidence that BPA is related to disease in women.
Open Access
An Update on Surgical versus Expectant Management of Ovarian Endometriomas in Infertile Women.
(BioMed research international, 2015-01) Keyhan, Sanaz; Hughes, Claude; Price, Thomas; Muasher, Suheil
Ovarian endometriomas are a common manifestation of endometriosis that can represent a more severe stage of the disease. There is much debate over the treatment of these cysts in infertile women, particularly before use of assisted reproductive technologies. Evidence exists that supports surgical excision of ovarian endometriomas, as well as evidence that cautions against surgical intervention. Certain factors need to be examined closely before proceeding with surgery or continuing with expectant management. These include the patient's symptoms, age, ovarian reserve, size and laterality of the cyst, prior surgical treatment, and level of suspicion for malignancy. The most recent evidence appears to suggest that certain patient profiles may benefit from proceeding directly to in vitro fertilization (IVF). These include symptomatic infertile patients, especially those that are older, those that have diminished ovarian reserve, those that have bilateral endometriomas, or those that have had prior surgical treatment. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman's ovarian reserve. Nevertheless, the presence of an endometrioma does not appear to adversely affect IVF outcomes, and surgical excision of endometriomas does not appear to improve IVF outcomes. Regardless of treatment plan, infertile patients with endometriomas must be counseled appropriately before choosing either treatment path.
Open Access
Beyond p-value: the Rigor and Power of Study
(Global Clinical and Translational Research, 2020-01-10) Zhang, Fengyu; Hughes, Claude
There have been a series of recent discussions and debates on the p-value and statistical significance. These discussions, including publications of more than 40 papers in a special issue of the American Statistician, provide an excellent opportunity to think about some technical measures for practical implementation in grant applications and publications. While several factors have been discussed, it may be the rigor of a study that determines the p-value for reporting study results and judging a consistent replication of research. Both p-values and power, which integrate Fisherian and Neyman-Pearson methods, should be used for hypothesis testing. We propose new criteria, which can be implemented without fundamental changes in existing statistics, to reduce false positives and irreplicability of studies that are either inadequately powered or overpowered.
Open Access
Clinical Epidemiology of Coronavirus Disease 2019: Defined on Current Research
(Global Clinical and Translational Research, 2020-07-25) Hughes, Claude; Zhang, Fengyu
Coronavirus disease 2019 (COVID-19) is a new infectious respiratory disease that has caused the ongoing global pandemic. The primary purpose of this article is to describe evolving clinical epidemiology of COVID-19, including 1) infection and testing, 2) clinical spectrum including classification of clinical type, asymptomatic cases, severe cases and comorbidity, and clinical and immunological response, 3) regional variation in clinical presentation, 4) population distribution by age, sex, and occupation, and finally, 5) case-fatality. This content may provide important information on detailed clinical type and presentation of the disease, in which appropriate clinical outcomes can be derived for developing prevention strategies and clinical studies or trials that aim to test potential therapeutics or products for different patient populations.
Open Access
Ecological Analysis of Gastroschisis Incidence Decline in Liaoning, China, 2006-2016
(Global Clinical and Translational Research, 2020-12-30) Li, Ruiping; Zhang, Fengyu; Hughes, Claude; Li, Jianxin
Background: A gastroschisis incidence decline has recently been reported in Liaoning, China, from 2006-2015; we suspect that this decline could be associated with the fall in industrial manufacturing activities. Methods: The outcome variable, gastroschisis incidence, was from a previous publication. The industrial manufacturing activities were measured by relative job participation and production in the primary and secondary economic sectors, and the corresponding data were collected in 14 cities from 2005 to 2015. The general linear model and a random-effect Poisson regression model were performed to assess the association and time-series trend of gastroschisis with the manufacturing activities. Results: The relative job participation in the first economic sector was marginally associated with gastroschisis incidence in 2006 (p=0.070), but more significantly associated (Beta=-0.040; p=0.014) in the cross-sectional and time-series analysis with one-year lag in the outcome variable. Conclusion: The gastroschisis incidence decline in Liaoning is likely due to the reduced job participation in manufacturing and heavy industry, which might be an indication of reduced risk exposure associated with the industrial manufacturing activities.
Open Access
Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir.
(Environmental and molecular mutagenesis, 2022-01) Waters, Michael D; Warren, Stafford; Hughes, Claude; Lewis, Philip; Zhang, Fengyu
This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, β-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.
Open Access
Interpretation of the Environmental Impact on Autism Spectrum Disorder
(Global Clinical and Translational Research, 2019-09-30) Zhang, Fengyu; Hughes, Claude
Comments on Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders. Cell Res. 2019. https://www.nature.com/articles/s41422-019-0220-1, PMID:31462724
Open Access
New Journal Launch: Global Clinical and Translational Research
(Global Clinical and Translational Research, 2019-03-30) Hughes, Claude; Zhang, Fengyu
We are proud to announce the launch of Global Clinical and Translational Research, a new journal that aims to promote clinical and translational research in the genomic era from a global perspective. The journal will (1) provide a unified platform of research communication for basic scientists, medical doctors, other clinical health professionals, social scientists and social workers to share the most recent advances in all areas of clinical and translational sciences; (2) introduce new techniques and methodology such as genomics-based techniques and approaches to design and perform a new generation of clinical research; (3) foster collaborative clinical research from a global perspective.
Open Access
Prenatal Environment and Perinatal Factors Associated with Autism Spectrum Disorder
(Global Clinical and Translational Research, 2019-09-30) Ou, Jianjun; Shen, Yidong; Li, Yamin; Xu, Guanglei; Liu, Huaqing; He, Yiqun; Guo, Hui; Wu, Renrong; Hughes, Claude; Xia, Kun; Zhao, Jingping; Zhang, Fengyu
Background: Both genetic and epidemiological studies have indicated that environmental factors play an essential role in the development of autism spectrum disorder (ASD). We conducted this study to identify maternal exposure to environmental factors, in particular during the fetal development or perinatal period, associated with ASD. Methods: Two independent samples of children with ASD and typical developed (TD) were from distinct regions in China. Multiple logistic regression analysis was performed to identify factors associated with ASD in each sample and then in the combined sample. Results: Five factors were consistently associated with ASD in both samples. In the combined sample, maternal chemical exposure (odds ratio [OR] =4.50; 95% CI: 2.38-8.52), use of medication (OR = 3.19; 95% CI: 2.19-4.65), maternal infection (OR = 2.68; 95% CI: 1.99-3.61), threatened abortion (OR = 2.37; 95% CI: 1.61-3.50), and induced abortion before having the child (OR = 2.07; 95% CI: 1.65-2.60) showed strong associations with ASD; moreover, five factors explained 10-15% of the variation in the risk of ASD. A significant interaction between maternal infection and the use of medication during pregnancy was consistently detected in both independent and combined samples together. Conclusion: Two novel risk factors of maternal chemical exposure and induced abortion may have important implications for understanding the etiology of ASD, particularly in China. Prospective studies are needed to validate these findings, and necessary interventions are recommended to reduce the risk of ASD. KEYWORDS Autism spectrum disorder, chemical exposure, induced abortion, maternal infection
Open Access
Real-World Observations from a First Season of the Rugby Union “Activate Programme” for Injury Risk Reduction in a U19 Men’s Team in North Carolina, USA
(Sports Injr Med, 2018-07-16) Hughes, Claude
Open Access
Reply to Comments on "Beyond P-value: the Rigor and Power of Study"
(Global Clinical and Translational Research, 2020-01-10) Zhang, Fengyu; Hughes, Claude
We received commentaries that included comments on our paper. Here we provide replies to the comments in the order received. To avoid confusion, we made a revision in the Table 1 to assure that level of significance and power at specified effect size are used appropriately.
Open Access
Reporting standards for clinical and translational research
(Global Clinical and Translational Research, 2019-04-16) Hughes, Claude; Zhang, Fengyu
Open Access
The Increasing Prevalence of Gastroschisis: Associated Factors, Possible Mechanisms, and Potential Mitigative Interventions
(Glob Clin Transl Res, 2019-01-28) Hughes, Claude; Adibe, O
Background: Gastroschisis has increased globally over recent decades and this increase is not explained by demographic changes in maternal age. Implicated risk factors for this increase include lifestyle behaviors, environmental exposures, low-er socioeconomic status, lower body mass index, poor nutrition, smoking tobacco, using illicit drugs, alcohol, or analgesics and genitourinary infections. Methods: Selective review of the literature. Results: Present hypotheses would only suggest avoidance of suspect exposures as protective interventions. To identify safe and efficacious protective therapies, new cellular/molecular modes-of-action need to be considered. Plausible develop-mental modes-of-action include a) changes in epigenetic programming of relevant stem or progenitor cells; b) mechanical forces (cellular mechanosensitivity and mechanotransduction) signaling; and c) ephrin–Eph receptor multimodal signali-ng. These developmental modes-of-action present plausible options for “druggable” molecules that could be developed into protective or mitigative therapeutic agents for gastroschisis. Conclusion: Possible interventions for modifiable factors in gastroschisis include 1) Delay childbearing. 2) Improve nutri-tion for younger gravidas. 3) Pre-conceptional counseling to reduce embryonic exposures to the range of implicated lifest-yle, environmental and medical factors. 4) Urge research colleagues to investigate the cellular and molecular mechanisms underlying gastroschisis and to translate those insights into one or more safe and efficacious preventive or mitigative thera-pies.
Open Access
Translational toxicology: a developmental focus for integrated research strategies.
(BMC pharmacology & toxicology, 2013-01) Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo
BACKGROUND: Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? DISCUSSION: Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. SUMMARY: Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.