Exploration of the nutrition knowledge among general population: multi-national study in Arab countries.

BACKGROUND: Knowing what to eat and realizing the significance of healthful eating habits are among the important steps to promoting eating behavior. The current study aims to assess the nutrition knowledge (NK) among a convenient sample in four different countries, determine the association between different demographic factors and NK, and investigate the need for future interventions on nutrition in the four selected countries. METHODS: A cross-sectional multi-national survey study among a convenient sample of 8,191 subjects from Egypt, Syria, Saudi Arabia, and Jordan who undertook surveys between January 2019 and January 2020. A pre-tested interview questionnaire was utilized for data collection from study participants. It included three sections: i) Sociodemographic characteristics:. ii). Section two included twenty-one questions related to NK.. iii). Section three included one question about NK sources. RESULTS: About three-quarters showed inadequate nutrition knowledge (73.1%). Youth (15-24 yrs.) were more dependent on social media, with 87% using it as a primary source of NK, while adults (≥ 25 yrs.) demonstrated that 43% of them used social media. In contrast, TV was more prominent among them, with participants' characteristics such as living with parents, body mass index, and country of residence showing no association with NK. However, female sex, education, and reading nutrition articles are significantly correlated with adequate knowledge (p < 0.001). Significant predictors of satisfactory knowledge were age, sex, education, living with parents, and reading nutrition articles. CONCLUSION: The study revealed low levels of NK indicating an urgent need to implement educational programs to promote nutrition knowledge. As NK is a modifiable determinant of diet intake and can positively impact the need for developing strategies in counselling and raising awareness among the general population to improve their health status.

Using a shortened uncuffed endotracheal tube as a nasopharyngeal airway: a useful adjunct during fiberoptic intubation training among anesthesia residents.

Background: Fiberoptic intubation (FOI) is considered a beneficial modality used to intubate life-threatening airway patients. This study aims at assessing the effectiveness of shortened uncuffed endotracheal tube as a nasopharyngeal airway during FOI. Methods: Between January 2019 and March 2021, this prospective randomized controlled trial has enrolled 62 adult patients (56 males and 6 females) with normal airways scheduled for elective oral FOI classified American Society of Anesthesiologists (ASA I-III), their age ranged 20-60 years. The patients were randomized into two equal groups (31 per each); in group I, FOI was carried using lingual traction, and in group II, FOI was carried out with lingual traction plus a shortened uncuffed endotracheal tube as a modified nasopharyngeal airway to maintain oxygenation. The time taken to successful tracheal intubation and other technical parameters have been measured. The heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO2), end-tidal carbon dioxide (EtCO2), and any associated complications have been measured. Results: During insertion of the scope, the SpO2 was significantly decreased in group I (92.55 ± 7.94) compared to group II (97.42 ± 6.34), p=0.009. The heart rate, MAP, and EtCO2 were found to be insignificantly different in both groups (p>0.05). The time needed for intubation in group I (2.78±0.98 min) was prolonged compared with group II (1.95±1.02 min) p =0.002. The number of attempts was comparable in both groups, while the number of successful intubations from the 1st attempt was 12 (39%) compared to 18 (58%) in groups I and II respectively, p=0.36. The overall success rate by juniors was 71% in group I compared to 84% in group II, p=0.66 with a lower incidence of using rescue oxygen and other facilitating maneuvers. Conclusions: The modified nasopharyngeal airway is a useful modality to facilitate oral FOI by anesthesia resident trainees.

Inspiratory muscle training for recovered COVID-19 patients after weaning from mechanical ventilation: A pilot control clinical study.

BACKGROUND: To the best of our knowledge, no studies have evaluated the effects of inspiratory muscle training (IMT) on recovered COVID-19 patients after weaning from mechanical ventilation. Therefore, this study assessed the efficacy of IMT on recovered COVID-19 patients following mechanical ventilation. METHODS: Forty-two recovered COVID-19 patients (33 men and 9 women) weaned from mechanical ventilation with a mean age of 48.05 ±â€Š8.85 years were enrolled in this pilot control clinical study. Twenty-one patients were equipped to 2-week IMT (IMT group) and 21 matched peers were recruited as a control (control group). Forced vital capacity (FVC%), forced expiratory volume in 1 second (FEV1%), dyspnea severity index (DSI), quality of life (QOL), and six-minute walk test (6-MWT) were assessed initially before starting the study intervention and immediately after intervention. RESULTS: Significant interaction effects were observed in the IMT when compared to control group, FVC% (F = 5.31, P = .041, ηP2 = 0.13), FEV1% (F = 4.91, P = .043, ηP2 = 0.12), DSI (F = 4.56, P = .032, ηP2 = 0.15), QOL (F = 6.14, P = .021, ηP2 = 0.17), and 6-MWT (F = 9.34, P = .028, ηP2 = 0.16). Within-group analysis showed a significant improvement in the IMT group (FVC%, P = .047, FEV1%, P = .039, DSI, P = .001, QOL, P < .001, and 6-MWT, P < .001), whereas the control group displayed nonsignificant changes (P > .05). CONCLUSIONS: A 2-week IMT improves pulmonary functions, dyspnea, functional performance, and QOL in recovered intensive care unit (ICU) COVID-19 patients after consecutive weaning from mechanical ventilation. IMT program should be encouraged in the COVID-19 management protocol, specifically with ICU patients.

Cost-effectiveness of neonatal surgery for congenital anomalies in low-income and middle-income countries: a systematic review protocol.

INTRODUCTION: Congenital anomalies are the fifth leading cause of death in children under 5 years old globally (591 000 deaths reported in 2016). Over 95% of deaths occur in low-income and middle-income countries (LMICs). It is estimated that two-thirds of the congenital anomaly health burden could be averted through surgical intervention and that such interventions can be cost-effective. This systematic review aims to evaluate current evidence regarding the cost-effectiveness of neonatal surgery for congenital anomalies in LMICs. METHODS AND ANALYSIS: A systematic literature review will be conducted in PubMed, MEDLINE, Embase, Cochrane Library, Scielo, Google Scholar, African Journals OnLine and Regional WHO's African Index Medicus databases for articles on the cost-effectiveness of neonatal surgery for congenital anomalies in LMICs. The following search strings will be used: (1) congenital anomalies; (2) LMICs; and (3) cost-effectiveness of surgical interventions. Articles will be uploaded to Covidence software, duplicates removed and the remaining articles screened by two independent reviewers. Cost information for interventions or procedures will be extracted by country and condition. Outcome measurements by reported unit and cost-effectiveness ratios will be extracted. Methodological quality of each article will be assessed using the Drummond checklist for economic evaluations. The Agency for Healthcare Research and Quality's Effective Health Care Program guidance will be followed to assess the grade of the studies. ETHICS AND DISSEMINATION: No ethical approval is required for conducting the systematic review. There will be no direct collection of data from individuals. The finalised article will be published in a scientific journal for dissemination. The protocol has been registered with PROSPERO (International Prospective Register of Systematic Reviews). CONCLUSION: Congenital anomalies form a large component of the global health burden that is amenable to surgical intervention. This study will systematically review the current literature on the cost-effectiveness of neonatal surgery for congenital anomalies in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020172971.

Protocol registration issues of systematic review and meta-analysis studies: a survey of global researchers.

BACKGROUND: Although protocol registration of systematic reviews/meta-analysis (SR/MA) is still not mandatory, it is highly recommended that authors publish their SR/MA protocols prior to submitting their manuscripts for publication as recommended by the Cochrane guidelines for conducting SR/MAs. our aim was to assess the awareness, obstacles, and opinions of SR/MA authors about the protocol registration process. METHODS: A cross-sectional survey study included the authors who published SR/MAs during the period from 2010 to 2016, and they were contacted for participation in our survey study. They were identified through the literature search of SR/MAs in Scopus database. An online questionnaire was sent to each participant via e-mail after receiving their approval to join the study. We have sent 6650 emails and received 275 responses. RESULTS: A total of 270 authors responses were complete and included in the final analysis. Our results has shown that PROSPERO was the most common database used for protocol registration (71.3%). The registration-to-acceptance time interval in PROSPERO was less than 1 month (99.1%). Almost half of the authors (44.2%) did not register their protocols prior to publishing their SR/MAs and according to their opinion that the other authors lack knowledge of protocol importance and mandance to be registered, was the most commonly reported reason (44.9%). A significant percenatge of respondents (37.4%) believed that people would steal their ideas from protocol databases, while only 5.3% reported that their SR/MA had been stolen. However, the majority (72.9%) of participants have agreed that protocol registries play a role in preventing unnecessary duplication of reviews. Finally, 37.4% of participants agree that SR/MA protocol registration should be mandatory. CONCLUSION: About half of the participants believes that the main reason for not registering protocols, is that the other authors lack knowledge concerning obligation and importance to register the SR/MA protocols in advance. Therefore, tools should be available to mandate protocol registration of any SRs beforehand and increasing awareness about the benefits of protocol registration among researchers.

Methodological steps used by authors of systematic reviews and meta-analyses of clinical trials: a cross-sectional study.

BACKGROUND: The quality of systematic reviews and meta-analyses (SR/MAs) depends on the extent of the methods used. We investigated the methodological steps used by authors of SR/MAs of clinical trials via an author survey. METHODS: We conducted an email-based cross-sectional study by contacting corresponding authors of SR/MAs that were published in 2015 and 2016 and retrieved through the PubMed database. The 27-item questionnaire was developed to study the methodological steps used by authors when conducting a SR/MA and the demographic characteristics of the respondent. Besides the demographic characteristics, methodological questions regarding the source, extraction and synthesis of data were included. RESULTS: From 10,292 emails sent, 384 authors responded and were included in the final analysis. Manual searches were carried out by 69.2% of authors, while 87.3% do updated searches, 49.2% search grey literature, 74.9% use the Cochrane tool for risk of bias assessment, 69.8% assign more than two reviewers for data extraction, 20.5% use digital software to extract data from graphs, 57.9% use raw data in the meta-analysis, and 43.8% meta-analyze both adjusted and non-adjusted data. There was a positive correlation of years of experience in conducting of SR/MAs with both searching grey literature (P = 0.0003) and use of adjusted and non-adjusted data (P = 0.006). CONCLUSIONS: Many authors still do not carry out many of the vital methodological steps to be taken when performing any SR/MA. The experience of the authors in SR/MAs is highly correlated with use of the recommended tips for SR/MA conduct. The optimal methodological approach for researchers conducting a SR/MA should be standardized.

Introduction of Novel Surgical Techniques: A Survey on Knowledge, Attitude, and Practice of Surgeons.

Purpose. To investigate the knowledge, attitude, and practice of surgeons toward introducing novel surgical techniques in Egypt, Palestine, and Vietnam. Summary Background Data. Despite the recent advances in modern surgical care and its role in advancing the quality and the length of lives, surgery in the developing world has stagnated or even regressed. Methods. A survey was undertaken among the surgeons in 9 hospitals belonging to the 3 countries. Questions were categorized into knowledge, attitude, and practice questions. Meta-analyses were performed to estimate the event rate and compare between knowledge and practice, senior and junior surgeons. Results. A total of 244 responses, with a response rate of 79.7%, were included in the analysis. Regarding knowledge and attitude, the results were satisfactory except that only 55.8% of surgeons appraised their level of education and 43.3% wanted to earn money from the novel procedure. There was a significant difference between knowledge and practice regarding getting informed consent from the patients (P = .024), discussing the novelty of the procedure (P < .001), discussing the alternative procedures (P < .001), discussing the surgeons' experience and level of skills (P < .001), discussing the risk of the new procedure (P < .001), and monitoring the outcomes after the new procedure (P < .001). Conclusions. Most surgeons have sufficient knowledge and are motivated regarding adopting novel surgical techniques in order to provide the best care for the patients. However, there was a gap between knowledge and practice. Training programs and evidence-based guidelines regarding the introduction of novel surgical techniques are needed to overcome these challenges.

MMP-2 and MMP-9 as prognostic markers for the early detection of urinary bladder cancer.

The present study assessed protein and gene expression levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), and MMP-9 in urine and blood samples of 50 patients with bladder carcinoma. The expression of TIMP-2, MMP-2, and MMP-9 levels with tumor stage and grade was also assessed. Results showed that the expression levels of MMP-2 and MMP-9 in both blood and urine were significantly elevated in group 1 when compared with groups 2 and 3 healthy subjects. The discriminatory ability in the diagnosis of bladder carcinoma of MMP-2 and MMP-9 expression was confirmed by receiver operating characteristic curve analysis that revealed a sensitivity and specificity of 100%. MMP-2 and MMP-9 levels were not correlated with grade or stage of the tumor. With respect to TIMP-2 blood and urine levels, results showed a significant decrease in gene expression levels in bladder carcinoma group, whereas, TIMP-2 protein showed a significant increase in bladder carcinoma.

Prediction of Pediatric Percutaneous Nephrolithotomy Outcomes Using Contemporary Scoring Systems.

PURPOSE: We evaluate the applicability of contemporary percutaneous nephrolithotomy scoring systems in pediatric patients and compare their predictive power regarding postoperative outcomes. MATERIALS AND METHODS: We retrospectively analyzed the records of 125 children who were diagnosed with renal calculi and underwent percutaneous nephrolithotomy between March 2011 and April 2016. Predictive scores, which consisted of Guy's Stone Score, S.T.O.N.E. (stone size, tract length, obstruction, number of involved calyces and essence/stone density) nephrolithometry and CROES (Clinical Research Office of the Endourological Society) nomogram, were calculated for all patients included in the study. Patient demographics, stone-free rate and complications were all analyzed and are reported. RESULTS: Median Guy's Stone Score was 2 (IQR 2 to 3) in patients with residual stones (group 1) and 2 (1 to 2) in those who were stone-free (group 2). Median respective CROES nomogram scores were 215 (IQR 210 to 235) and 257 (240 to 264), and S.T.O.N.E. nephrolithometry scores were 8 (7 to 9) and 5 (5 to 6, all p <0.0001). S.T.O.N.E. score demonstrated the greatest accuracy in predicting stone-free rate. Guy's Stone Score was significantly correlated with complications but the CROES and S.T.O.N.E. scores were not significantly correlated with complications. CONCLUSIONS: The scoring systems analyzed could be used to predict success of percutaneous nephrolithotomy in the pediatric setting. However, further studies are needed to formulate modifications for use in children. The main variables in the scoring systems, ie stone burden, tract length and case volume, were measured using records from adult patients. Besides these variables, the relatively small pelvicalyceal system and higher incidence of anatomical malformations in children could potentially affect percutaneous nephrolithotomy outcomes.

Internal versus external ureteric stents for uretero-ileal anastomosis after laparoscopic radical cystectomy with orthotopic neobladder: A prospective comparative study.

OBJECTIVE: To prospectively compare the use of external ureteric stents with internal JJ stenting of the uretero-ileal anastomosis in patients undergoing laparoscopic radical cystectomy (LRC) with a Y-shaped ileal orthotopic neobladder (ON). PATIENTS AND METHODS: The study included 69 patients undergoing LRC with ON. Patients were grouped according to the type of uretero-ileal stents used. An external ureteric stent was used in Group A (33 patients) and a JJ stent was used in Group B (36). We prospectively compared the duration of hospital stay, the incidence of short- and intermediate-term complications in the two study groups. RESULTS: The mean (SD) follow-up periods were 29.18 (3.94) and 28.19 (3.37) months for patients in Groups A and B, respectively. Perioperative patient characteristics were comparable in the two study groups. The use of JJ stenting was associated with a shorter hospital stay compared with external stenting, at a mean (SD) of 14.63 (3.74) and 6.8 (3.03) days in Groups A and B, respectively (P < 0.001). The incidence of urinary leakage was comparable in the two study groups, at 6.1% in Group A vs 8.3% in Group B (P = 1.0). Strictures of the uretero-ileal anastomosis occurred in two patients (6%) in Group A and confirmed by intravenous urography. All strictures were treated with antegrade JJ fixation. CONCLUSION: JJ stents could be used as an effective alternative to external ureteric stents to support the uretero-ileal anastomosis. JJ stenting is associated with a shorter hospital stay and similar complication rates compared with external stenting in patients undergoing LRC with ON.

The effect of environmental chemicals on the tumor microenvironment.

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.

Disruptive chemicals, senescence and immortality.

Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.

Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.

One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.

The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis.

The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Environmental immune disruptors, inflammation and cancer risk.

An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented.

Causes of genome instability: the effect of low dose chemical exposures in modern society.

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.