Nociplastic pain: towards an understanding of prevalent pain conditions.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Intolerance of loud sounds in childhood: Is there an intergenerational association with grandmaternal smoking in pregnancy?

Recent research using the Avon Longitudinal Study of Parents and Children (ALSPAC) demonstrated an association between maternal grandmother smoking in pregnancy and the autistic traits of impaired social communication and repetitive behaviour in granddaughters but not grandsons, but of paternal grandmother smoking and early development of myopia in the grandchild. Here we investigate whether grandmaternal smoking in pregnancy is associated with intolerance to loud sounds. ALSPAC collected information during the index pregnancy from the study parents on the smoking habits, social and other features of their own parents. Maternal report when the child was aged 6 and 13 included hating loud sounds; at age 11 the child was tested for volume preference for listening to music through headphones. Statistical analysis compared results for grandchildren in relation to whether a parent had been exposed in utero to maternal smoking, adjusted for their grandparents' social and demographic attributes. We hypothesised that there would be sex differences in the effects of grandmaternal prenatal smoking, based on previous intergenerational studies. For 6-year-old children maternal report of intolerance to loud noise was more likely in grandsons if the maternal grandmother had smoked [adjusted odds ratio (AOR) 1.27; 95% confidence interval (CI) 1.03,1.56; P = 0.025], but less likely in girls [AOR 0.82; 95%CI 0.63,1.07] Pinteraction <0.05. If the paternal grandmother had smoked the grandchildren were less likely to be intolerant, especially girls. The objective measure of choice of volume for music through headphones showed that grandsons of both maternal and paternal smoking grandmothers were less likely to choose high volumes compared with granddaughters (P<0.05). In line with our prior hypothesis of sex differences, we showed that grandsons were more intolerant of loud sounds than granddaughters particularly at age 6, and this was confirmed by objective measures at age 11.

Pathogenic Mechanisms and Therapeutic Implication in Nickel-Induced Cell Damage.

BACKGROUND: Nickel (Ni) is mostly applied in a number of industrial areas such as printing inks, welding, alloys, electronics and electrical professions. Occupational or environmental exposure to nickel may lead to cancer, allergy reaction, nephrotoxicity, hepatotoxicity, neurotoxicity, as well as cell damage, apoptosis and oxidative stress. METHODS: In here, we focused on published studies about cell death, carcinogenicity, allergy reactions and neurotoxicity, and promising agents for the prevention and treatment of the toxicity by Ni. RESULTS: Our review showed that in the last few years, more researches have focused on reactive oxygen species formation, oxidative stress, DNA damages, apoptosis, interaction with involving receptors in allergy and mitochondrial damages in neuron induced by Ni. CONCLUSION: The collected data in this paper provide useful information about the main toxicities induced by Ni, also, their fundamental mechanisms, and how to discover new ameliorative agents for prevention and treatment by reviewing agents with protective and therapeutic consequences on Ni induced toxicity.

Impact of Heavy Metals on Host Cells: Special Focus on Nickel-Mediated Pathologies and Novel Interventional Approaches.

BACKGROUND: Heavy metals [arsenic, aluminium, cadmium, chromium, cobalt, lead, nickel (Ni), palladium and titanium] are environmental contaminants able to impact with host human cells, thus, leading to severe damage. OBJECTIVE: In this review, the detrimental effects of several heavy metals on human organs will be discussed and special emphasis will be placed on Ni. In particular, Ni is able to interact with Toll-like receptor-4 on immune and non-immune cells, thus, triggering the cascade of pro-inflammatory cytokines. Then, inflammatory and allergic reactions mediated by Ni will be illustrated within different organs, even including the central nervous system, airways and the gastrointestinal system. DISCUSSION: Different therapeutic strategies have been adopted to mitigate Ni-induced inflammatoryallergic reactions. In this context, the ability of polyphenols to counteract the inflammatory pathway induced by Ni on peripheral blood leukocytes from Ni-sensitized patients will be outlined. In particular, polyphenols are able to decrease serum levels of interleukin (IL)-17, while increasing levels of IL- 10. These data suggest that the equilibrium between T regulatory cells and T helper 17 cells is recovered with IL-10 acting as an anti-inflammatory cytokine. In the same context, polyphenols reduced elevated serum levels of nitric oxide, thus, expressing their anti-oxidant potential. Finally, the carcinogenic potential of heavy metals, even including Ni, will be highlighted. CONCLUSION: Heavy metals, particularly Ni, are spread in the environment. Nutritional approaches seem to represent a novel option in the treatment of Ni-induced damage and, among them, polyphenols should be taken into consideration for their anti-oxidant and anti-inflammatory activities.

Neurotransmitters and Behavioral Alterations Induced by Nickel Exposure.

BACKGROUND: Nickel ions (Ni2+) are a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for brain dysfunction and behavioral and neurological symptoms in humans. METHODS: We reviewed the current evidence about neurochemical and behavioral alterations associated with Ni exposure in laboratory animals and humans. RESULTS: Ni2+ exposure can alter (both inhibition and stimulation) dopamine release and inhibit glutamate NMDA receptors. Few reports claim an effect of Ni2+ at the level of GBA and serotonin neurotransmission. At behavioral levels, exposure to Ni2+ in rodents alters motor activity, learning and memory as well as anxiety and depressive-like symptoms. However, no analysis of the dose-dependent relationship has been carried out regarding these effects and the levels of the Ni2+ in the brain, in blood or urine. CONCLUSION: Further research is needed to correlate the concentration of Ni2+ in biological fluids with specific symptoms/deficits. Future studies addressing the impact of Ni2+ under environmental or occupational exposure should consider the administration protocols to find Ni2+ levels similar in the general population or occupationally exposed workers.

Respiratory gases, air pollution and epilepsy.

A growing number of studies have shown that exposure to air pollutants such as particulate matter and gases can cause cardiovascular, neurodegenerative and psychiatric diseases. The severity of the changes depends on several factors such as exposure time, age and gender. Inflammation has been considered as one of the main factors associated with the generation of these diseases. Here we present some cellular mechanisms activated by air pollution that may represent risk factors for epilepsy and drug resistance associated to epilepsy.

Occurrence of heavy elements in street dust from sub/urban zone of Tianjin: pollution characteristics and health risk assessment.

Main purpose of this study was to determine the concentrations of selected heavy elements (As, Cd, Pb, Cu, Co, Cr and Ni) in the street dust samples (n = 49) collected from seven districts located in suburban/urban zone of Tianjin in order to estimate their possible sources and degree of environmental pollution as well as human health risk. Mean concentrations (mg kg-1) of As (19.3), Cd (0.60), Pb (28.4) and Cu (62.7) were above their corresponding soil background values. According to the results of multivariate statistical analysis, the accumulation of As, Cd, Pb, Cu and Cr in street dust was affected by anthropogenic activities, while the contents of Ni and Co were associated with natural sources. Pollution degree by geo-accumulation index had the following trend: Cd > Cu > As > Pb > Cr > Ni > Co. Dust contamination with Cd ranged from unpolluted to highly polluted. Potential ecological risk indicated low (Pb, Cu, Cr, Co and Ni) to high (Cd) risk, while potential risk index showed moderate and very high risks. Non-carcinogenic risk of the studied elements was below safe level (<1). Data obtained in this investigation gave the additional values to the knowledge needed for future monitoring and risk assessment, relating the presence of heavy elements studied in suburban/urban areas.

Evaluation of PM1, PM2.5, and PM10 exposure and the resultant health risk of preschool children and their caregivers.

Preschool children have a higher respiratory rate per unit body weight than adults, and their respiratory systems are not mature. Hence, children may have more health risks associated with particulate matter (PM) exposure. In this study, we assessed the exposure of preschool children and their caregivers to PM and the resulting health risks. The PM concentrations at heights of 60-80 cm (preschool children) and 150 cm (adults) were measured at ten indoor and eight outdoor sites in the Taipei metropolitan area from March 2015 to February 2017. Four PM2.5 and seven PM10 indoor measurements exceeded the indoor air quality standard of Taiwan, whereas only two PM2.5 outdoor measurements exceeded the ambient air quality standard. The outdoor PM concentrations were related to traffic emissions, whereas the indoor PM concentrations were associated with ventilation rate and occupant density. The chronic daily PM1, PM2.5, and PM10 intakes of preschool children were notably higher than those of adults. In addition, the hazard quotient resulting from PM2.5 exposure indicated a significant health risk for preschool children (93.74% greater than 1). Consequently, reducing the exposure of preschool children to PM2.5 is an emerging issue in the Taipei metropolitan area.

Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring.

Human health is dependent upon environmental exposures, yet the diversity and variation in exposures are poorly understood. We developed a sensitive method to monitor personal airborne biological and chemical exposures and followed the personal exposomes of 15 individuals for up to 890 days and over 66 distinct geographical locations. We found that individuals are potentially exposed to thousands of pan-domain species and chemical compounds, including insecticides and carcinogens. Personal biological and chemical exposomes are highly dynamic and vary spatiotemporally, even for individuals located in the same general geographical region. Integrated analysis of biological and chemical exposomes revealed strong location-dependent relationships. Finally, construction of an exposome interaction network demonstrated the presence of distinct yet interconnected human- and environment-centric clouds, comprised of interacting ecosystems such as human, flora, pets, and arthropods. Overall, we demonstrate that human exposomes are diverse, dynamic, spatiotemporally-driven interaction networks with the potential to impact human health.

[Air pollution and health]. / Luchtverontreiniging en gezondheid.

The effects of air pollution on health have been generating attention for years. A large number of pulmonologists have recently expressed concerns about this in an open letter to Dutch Members of Parliament. Air pollution arises mainly in all kinds of combustion processes; in addition, atmospheric chemical reactions play a role in the formation of ozone and particulate matter. Health effects are both acute (increase in daily mortality and morbidity after days with increased concentrations of air pollution) as well as chronic (shortened life span and increased incidence of respiratory and cardiovascular diseases in areas with elevated concentrations of air pollution). These effects already occur at concentrations that are clearly lower than those currently observed in the Netherlands.

Impact of improved cookstoves on women's and child health in low and middle income countries: a systematic review and meta-analysis.

OBJECTIVES: Improved biomass cookstoves may help reduce the substantial global burden of morbidity and mortality due to household air pollution (HAP) that disproportionately affects women and children in low and middle income countries (LMICs). DESIGN: Systematic review and meta-analysis of (quasi-)experimental studies identified from 13 electronic databases (last update: 6 April 2018), reference and citation searches and via expert consultation. SETTING: LMICs PARTICIPANTS: Women and children INTERVENTIONS: Improved biomass cookstoves MAIN OUTCOME MEASURES: Low birth weight (LBW), preterm birth, perinatal mortality, paediatric acute respiratory infections (ARIs) and COPD among women. RESULTS: We identified 53 eligible studies, including 24 that met prespecified design criteria. Improved cookstoves had no demonstrable impact on paediatric lower ARIs (three studies; 11 560 children; incidence rate ratio (IRR)=1.02 (95% CI 0.84 to 1.24)), severe pneumonia (two studies; 11 061 children; IRR=0.88 (95% CI 0.39 to 2.01)), LBW (one study; 174 babies; OR=0.74 (95% CI 0.33 to 1.66)) or miscarriages, stillbirths and infant mortality (one study; 1176 babies; risk ratio (RR) change=15% (95% CI -13 to 43)). No (quasi-)experimental studies assessed preterm birth or COPD. In observational studies, improved cookstoves were associated with a significant reduction in COPD among women: two studies, 9757 participants; RR=0.74 (95% CI 0.61 to 0.90). Reductions in cough (four studies, 1779 participants; RR=0.72 (95% CI 0.60 to 0.87)), phlegm (four studies, 1779 participants; RR=0.65 (95% CI 0.52 to 0.80)), wheezing/breathing difficulty (four studies; 1779 participants; RR=0.41 (95% CI 0.29 to 0.59)) and conjunctivitis (three studies, 892 participants; RR=0.58 (95% CI 0.43 to 0.78)) were observed among women. CONCLUSION: Improved cookstoves provide respiratory and ocular symptom reduction and may reduce COPD risk among women, but had no demonstrable child health impact. REGISTRATION: PROSPERO: CRD42016033075.

Physical and chemical trigger factors in environmental intolerance.

BACKGROUND: Individuals with environmental intolerance (EI) react to exposure from different environmental sources at levels tolerated by most people and that are below established toxicological and hazardous thresholds. The main aim of this study was to determine the prevalence of attributing symptoms to chemical and physical sources in the environment among individuals with different forms of self-reported EI and in referents. METHODS: Cross-sectional data from a population-based study, the Västerbotten Environmental Health Study (n = 3406), were used and individuals with self-reported EI to chemicals, buildings, electromagnetic fields and sounds as well as a group with multiple EIs were identified. The Environmental-Symptom Attribution Scale was used to quantify degree to which health symptoms are attributed to 40 specific environmental exposures and sources, with subscales referring to the four types of EI. RESULTS: All EI groups, except the group with building related intolerance (BRI), reported more symptoms from the expected sources compared to the referents. In addition, individuals with chemical and sound intolerance reported symptoms from building related trigger factors, and individuals with electromagnetic hypersensitivity reported symptoms from chemical trigger factors. CONCLUSIONS: The study suggests that individuals with BRI react to fewer and more specific trigger factors than do individuals with other EIs, and that it is important to ask about different sources since three of the EI groups attribute their symptoms to a wide variety of sources in addition to the sources to which their EI implicates.

[Health and environment, prevention or precaution?] / Santé et environnement, prévention ou précaution ?

The health status of the populations of developed countries has never been as satisfactory, but will it stay that way? Research on the subject is difficult due to the complex interactions between our environment and our health, with risks inherent to each noxious agent. Preventing the risks proven to be linked to the quality of our living environments is usually the responsibility of authorities, but individuals can also adopt precautionary practices.

[Environmental health education]. / L'éducation à la santé environnementale.

Environmental health education aims to reduce the impact of risk factors for patients. The caregiver's role is to adopt a positive education approach with concrete ways of controlling the living environment. He or she must support people in asserting their choices in terms of health and to make their own contribution to reducing risks.

Neighborhood Disorder and Sleep Problems in Older Adults: Subjective Social Power as Mediator and Moderator.

BACKGROUND AND OBJECTIVES: Contextual contributors to sleep problems are important to examine among older adults because sleep problems are associated with a number of adverse outcomes in late life. We examine whether disordered neighborhoods are a key contextual determinant of sleep problems in late life, as well as how subjective social power-a sense of personal control and subjective social status-mediates and moderates this association. Central to this contribution is the use of econometric techniques that holistically control for time-stable factors that may bias estimated associations. RESEARCH DESIGN AND METHODS: Three waves (2006, 2010, 2014) of the psychosocial subsample of the Health and Retirement Study (N = 7,130) are analyzed with random-effects models that adjust for repeated observations, as well as fixed-effects models that additionally control for all time-stable confounders. RESULTS: Neighborhood disorder is associated with greater sleep problems in random-effects models, but this association is substantially weakened in a fixed-effects model. Personal control mediates this association, but does not moderate it. Subjective social status does not mediate the association, but does moderate it. DISCUSSION AND IMPLICATIONS: Although neighborhood disorder is associated with sleep problems in older adults, this association is likely to be overestimated in analyses that do not compressively control for time-stable confounders. Rather than acting as dual mediators and moderators, perceived control and subjective social status play distinct roles in this association, with seniors at lower levels of subjective social status especially at risk for sleep problems due to neighborhood disorder.

Endocrine Disruptors and Developmental Origins of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide, particularly in countries that consume a Western diet, and can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma. With increasing prevalence of NAFLD in both children and adults, an understanding of the factors that promote NAFLD development and progression is crucial. Environmental agents, including endocrine-disrupting chemicals (EDCs), which have been linked to other diseases, may play a role in NAFLD development. Increasing evidence supports a developmental origin of liver disease, and early-life exposure to EDCs could represent one risk factor for the development of NAFLD later in life. Rodent studies provide the strongest evidence for this link, but further studies are needed to define whether there is a causal link between early-life EDC exposure and NAFLD development in humans. Elucidating the molecular mechanisms underlying development of NAFLD in the context of developmental EDC exposures may identify biomarkers for people at risk, as well as potential intervention and/or therapeutic opportunities for the disease.

Personal exposure to fine particulate matter and benzo[a]pyrene from indoor air pollution and leukocyte mitochondrial DNA copy number in rural China.

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-µg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.