Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here

Provincial screening rates for chronic diseases of lifestyle, cancers and HIV in a health-insured population

Background. Screening for asymptomatic diseases can reduce the burden of morbidity and mortality in all population groups. There is widespread geographical variation in the quality of care. Few data are available on national screening rates in South Africa and how these vary across the provinces.Objective. To examine screening rates for chronic diseases of lifestyle (CDL), HIV and cancer in a privately insured population for a singleinsurer across all nine provinces in South Africa, and to determine whether or not there are any differences between the provinces.Method. Screening rates were calculated as the proportion of eligible members who had received screening tests during 2011 in eachprovince. Mean screening rates were compared between Gauteng and the other eight provinces.Results. Nationwide screening rates were 20.5% for CDL, 8.2% for HIV and 31.9% for cancer. Despite similar insurance coverage, screening ratesranged from 0.3% to 0.95% lower in other provinces compared with Gauteng. Of all the provinces, Gauteng had the highest annual screeningrates for CDL, breast cancer, prostate cancer and HIV (p<0.001), while the Western Cape had the highest rate for cervical cancer (p<0.001).Conclusion. There is much variation in preventive care utilisation across the provinces within this health-insured population. Provinces with more abundant healthcare resources have higher screening rates. Further research is required to understand the reasons for the variation, given equal payment access

Strategic approaches to informing the public about biotechnology in Latin America

The benefits of today's biotechnology products are not evident to consumers. The public will accept biotechnology only when individuals decide for themselves that biotec products will contribute to their personal well-being. To make such a decision, people will need greater awareness and understanding of how biotechnology will affect the environment, human health, local and national economies, and the well-being of society. A low level of awareness and understanding about biotechnology is characteristic of Latin America and the Caribbean countries, as elsewhere, efforts to remedy poor public perception often seem inadequate and do not reflect a well-designed strategy. In order to improve the understanding of the biotechnology and their human applications, a strategic plan for public communications is required. Specific objectives for this initiative may include: (1) to make evident to decision makers that modern biotechnology can be an effective tool for increasing agricultural productivity, and thereby economic growth, without imposing unacceptable risk to the environment or human and animal health; (2) to enable members of the public to make informed decisions about appropriate uses of biotechnology by providing accurate information about benefits, risks and impacts; or (3) to incorporate modern biotechnology into science curricula for secondary schools, university and college students, and agriculture extension officers. A variety of specialized expertise, including communication specialists, technical writers, graphic artists and illustrators to design information materials and conduct training is needed to implement this. Ideally, members bring expertise in biotechnology and biosafety, public communications and project management. The plan will need to identify scientists and technical experts who can provide expertise in science writing for general audiences, advertising, graphic arts, public opinion polling and media communications. These people can provide basic information about the techniques of modern biotechnology; the products now available and those being developed; what is known about the nature, probability and consequences of potential risks. Governments, industry, universities and media must play an important role to improve public perception about biotechnology, this is a requirement to develop biotechnology in the Region

Notes on the feeding habits of the Caribbean Watersnake, Tretanorhinus variabilis (Dipsadidae)

The Caribbean Watersnake, Tretanorhinus variabilis (Dipsadidae) is one of two aquatic West Indian snakes. Despite being a relatively common species in Cuba and the Cayman Islands, its feeding habits have been poorly stud­ied. Herein we report several new instances of predation by this species on fishes, frogs, and a freshwater crab. The latter represents the first record of durophagy in this species and the third snake reported as a crab eater in the West Indies. &nbsp

Central deficiency of IL-6Ra in mice impairs glucose-stimulated insulin secretion

OBJECTIVE: IL-6 is an important contributor to glucose and energy homeostasis through changes in whole-body glucose disposal, insulin sensitivity, food intake and energy expenditure. However, the relative contributions of peripheral versus central IL-6 signaling to these metabolic actions are presently unclear. A conditional mouse model with reduced brain IL-6Ra expression was used to explore how blunted central IL-6 signaling alters metabolic status in lean and obese mice. METHODS: Transgenic mice with reduced levels of central IL-6 receptor alpha (IL-6Ra) (IL-6Ra KD mice) and Nestin Cre controls (Cre(+/-) mice) were fed standard chow or high-fat diet for 20 weeks. Obese and lean mouse cohorts underwent metabolic phenotyping with various measures of energy and glucose homeostasis determined. Glucose-stimulated insulin secretion was assessed in vivo and ex vivo in both mouse groups. RESULTS: IL-6Ra KD mice exhibited altered body fat mass, liver steatosis, plasma insulin, IL-6 and NEFA levels versus Cre(+/-) mice in a diet-dependent manner. IL-6Ra KD mice had increased food intake, higher RER, decreased energy expenditure with diminished cold tolerance compared to Cre(+/-) controls. Standard chow-fed IL-6Ra KD mice displayed reduced plasma insulin and glucose-stimulated insulin secretion with impaired glucose disposal and unchanged insulin sensitivity. Isolated pancreatic islets from standard chow-fed IL-6Ra KD mice showed comparable morphology and glucose-stimulated insulin secretion to Cre(+/-) controls. The diminished in vivo insulin secretion exhibited by IL-6Ra KD mice was recovered by blockade of autonomic ganglia. CONCLUSIONS: This study shows that central IL-6Ra signaling contributes to glucose and energy control mechanisms by regulating food intake, energy expenditure, fuel flexibility and insulin secretion. A plausible mechanism linking central IL-6Ra signaling and pancreatic insulin secretion is through the modulation of autonomic output activity. Thus, brain IL-6 signaling may contribute to the central adaptive mechanisms engaged in response to metabolic stress

Working on wellness (WOW): a worksite health promotion intervention programme

Background: Insufficient PA has been shown to cluster with other CVD risk factors including insufficient fruit and vegetable intake, overweight, increased serum cholesterol concentrations and elevated blood pressure. This paper describes the development of Working on Wellness (WOW), a worksite intervention program incorporating motivational interviewing by wellness specialists, targeting employees at risk. In addition, we describe the evaluation the effectiveness of the intervention among employees at increased risk for cardiovascular disease. Methods: The intervention mapping (IM) protocol was used in the planning and design of WOW. Focus group discussions and interviews with employees and managers identified the importance of addressing risk factors for CVD at the worksite. Based on the employees preference for individual counselling, and previous evidence of the effectiveness of this approach in the worksite setting, we decided to use motivational interviewing as part of the intervention strategy. Thus, as a cluster-randomised, controlled control trial, employees at increased risk for CVD (N = 928) will be assigned to a control or an intervention group, based on company random allocation. The sessions will include motivational interviewing techniques, comprised of two face-to-face and four telephonic sessions, with the primary aim to increase habitual levels of PA. Measures will take place at baseline, 6 and 12 months. Secondary outcomes include changes in nutritional habits, serum cholesterol and glucose concentrations, blood pressure and BMI. In addition, healthcare expenditure and absenteeism will be measured for the economic evaluation. Analysis of variance will be performed to determine whether there were significant changes in physical activity habits in the intervention and control groups at 6 and 12 months. Discussion: The formative work on which this intervention is based suggests that the strategy of targeting employees at increased risk for CVD is preferred. Importantly, this study extends the work of a previous, similar study, Health Under Construction, in a different setting. Finally, this study will allow an economic evaluation of the intervention that will be an important outcome for health care funders, who ultimately will be responsible for implementation of such an intervention. Trial registration: United States Clinical Trails Register NCT 01494207

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Similar to previous pandemics, COVID-19 has been succeeded by well-documented postinfectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood– brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement

Smart processes for smart buildings : ‘sustainable processes’, ‘recyclable processes’ and ‘building seeds’ in parametric design

The rapid evolution of digital technologies and the resulting emergence of novel design methodologies are coinciding with climate change, population growth and increased pressure on global resources. This concurrence evokes opportunities to harness the new design methods to develop smart design solutions and processes that respond effectively to sustainability requirements. Meanwhile, parametric design is emerging as an ideal design methodology to support sustainably in design, whereby the associative parameters in parametric design systems enable automation and synchronicity in generating design forms and evaluating these forms against their environmental performance. This research explores the multifaceted way in which parametric design supports sustainability, and how this can lead to a more holistic understanding of sustainability by shifting the focus from sustainable buildings to sustainable processes. In addition, the work shows how the reusability of parametric definitions in parametric design applications can enable designers to recycle the design process, where a parametric definition acts as a building seed that can be ’planted’ in different projects to automatically generate different forms. This may enable practitioners from all over the world to collectively develop a ‘seed library’ that has the potential for architects to empower, automate and enhance the environmental values of their processes. To achieve this, the main changes and shifts in computational design are reviewed, together with the impact of parametric design and its related applications on the architectural design process. In addition, a case study is conducted to explore how parametric design can significantly accelerate processes in real practice, and how the overlooked potential of reusing parametric definitions can make distinctive results in real architectural projects. Finally, the efficiency of the seed library is discussed as opposed to the apparent issues such as validity of seeds, motivation for sharing, and copyright