Modulation of gut microbiota with probiotics as a strategy to counteract endogenous and exogenous neurotoxicity.

The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.g., LPS, glucose, Aß, phospho-tau, α-synuclein) agents. Although the protective mechanisms of probiotic treatments differ between various neurotoxic agents, several key mechanisms at both the intestinal and brain levels seem inherent to all of them. Specifically, probiotic-induced improvement in gut microbiota diversity and taxonomic characteristics results in modulation of gut-derived metabolite production with increased secretion of SFCA. Moreover, modulation of gut microbiota results in inhibition of intestinal absorption of neurotoxic agents and their deposition in brain. Probiotics also maintain gut wall integrity and inhibit intestinal inflammation, thus reducing systemic levels of LPS. Centrally, probiotics ameliorate neurotoxin-induced neuroinflammation by decreasing LPS-induced TLR4/MyD88/NF-κB signaling and prevention of microglia activation. Neuroprotective mechanisms of probiotics also include inhibition of apoptosis and oxidative stress, at least partially by up-regulation of SIRT1 signaling. Moreover, probiotics reduce inhibitory effect of neurotoxic agents on BDNF expression, on neurogenesis, and on synaptic function. They can also reverse altered neurotransmitter metabolism and exert an antiamyloidogenic effect. The latter may be due to up-regulation of ADAM10 activity and down-regulation of presenilin 1 expression. Therefore, in view of the multiple mechanisms invoked for the neuroprotective effect of probiotics, as well as their high tolerance and safety, the use of probiotics should be considered as a therapeutic strategy for ameliorating adverse brain effects of various endogenous and exogenous agents.

Retinal toxicity of heavy metals and its involvement in retinal pathology.

The objective of the present review is to discuss epidemiological evidence demonstrating the association between toxic metal (Cd, Pb, Hg, As, Sn, Ti, Tl) exposure and retinal pathology, along with the potential underlying molecular mechanisms. Epidemiological studies demonstrate that Cd, and to a lesser extent Pb exposure, are associated with age-related macular degeneration (AMD), while the existing evidence on the levels of these metals in patients with diabetic retinopathy is scarce. Epidemiological data on the association between other toxic metals and metalloids including mercury (Hg) and arsenic (As), are limited. Clinical reports and laboratory in vivo studies have shown structural alterations in different layers of retina following metal exposure. Examination of retina samples demonstrate that toxic metals can accumulate in the retina, and the rate of accumulation appears to increase with age. Experimental studies in vivo and in vitro studies in APRE-19 and D407 cells demonstrate that toxic metal exposure may cause retinal damage through oxidative stress, apoptosis, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, impaired retinogenesis, and retinal inflammation. However, further epidemiological as well as laboratory studies are required for understanding the underlying molecular mechanisms and identifying of the potential therapeutic targets and estimation of the dose-response effects.

Hair and Serum Trace Element and Mineral Levels Profiles in Women with Premenopausal and Postmenopausal Osteoporosis.

The objective of the present study was to evaluate serum and hair trace element and mineral levels in women with osteoporosis, as well as to estimate the impact of menopausal status on the profile of trace element and mineral status in women with osteoporosis. 207 women with diagnosed osteoporosis 22-85 years-of-age, and 197 healthy women of the respective age participated in the present study. Analysis of the levels of mineral and trace element in hair and serum samples was performed by inductively-coupled plasma mass-spectrometry (ICP-MS). Women with osteoporosis were characterized by significantly lower hair Ca, Mg, Co, I, Li, and Mn levels, as well as serum Ca, Mg, Co, Fe, V, and Zn concentrations compared to women in the control group. After additional grouping according to menopausal status, the lowest hair Ca and Mg content was observed in postmenopausal osteoporotic women, whereas serum Ca and Mg concentrations were the lowest in premenopausal osteoporotic women. Hair Co, Mn, and Zn levels in postmenopausal osteoporotic women were lower than in healthy postmenopausal women. The lowest circulating Zn levels were observed in osteoporotic postmenopausal women. Taken together, decreased hair and serum levels in osteoporotic women are indicative of increased risk of Ca, Mg, Co, and Zn deficiency in women with osteoporosis. In turn, alterations in hair trace element and mineral levels in osteoporosis are more profound in postmenopausal women. Hypothetically, improvement in trace element and mineral metabolism especially in postmenopausal women may be considered as a potential strategy for mitigating osteoporosis.

COVID-19 vaccination and case fatality rates: a case report in a Brazilian municipality.

Vaccination campaigns played a crucial role in reducing the incidence of COVID-19. However, a scant number of studies evaluated the impact of vaccination on case fatality rates (CFRs), including in Brazil. Our study aimed to compare CFRs according to vaccination status among subjects living in Arapongas (Paraná State, Brazil), considering the age composition of the population. Several strategies adopted by the Arapongas City Hall to minimize the spread of the virus were also elaborated upon. We accessed the 2021 database of the Arapongas Municipal Health Department, in which a total of 16,437 confirmed cases and 425 deaths were reported. The CFR was calculated as the ratio between COVID-19 deaths and the number of confirmed cases. Differences in age composition between unvaccinated and fully vaccinated individuals were observed in our study. Considering that CFR is a crude indicator and is highly sensitive to the age composition of the population, we adopted the average age distribution of confirmed cases among the three vaccination statuses (unvaccinated, partially, and fully) as a standard age distribution. The age-standardized CFR for unvaccinated and fully vaccinated groups were 4.55% and 2.42%, respectively. Fully vaccinated individuals showed lower age-specific CFRs in all age groups above 60 years than unvaccinated populations. Our findings strengthen the role of vaccination as a critical measure for preventing deaths among infected people and is particularly important to the ongoing reassessment of public health interventions and policies.

Probabilistic survival modeling in health research: an assessment using cohort data from hospitalized patients with COVID-19 in a Latin American city.

Probabilistic survival methods have been used in health research to analyze risk factors and adverse health outcomes associated with COVID-19. The aim of this study was to employ a probabilistic model selected among three distributions (exponential, Weibull, and lognormal) to investigate the time from hospitalization to death and determine the mortality risks among hospitalized patients with COVID-19. A retrospective cohort study was conducted for patients hospitalized due to COVID-19 within 30 days in Londrina, Brazil, between January 2021 and February 2022, registered in the database for severe acute respiratory infections (SIVEP-Gripe). Graphical and Akaike Information Criterion (AIC) methods were used to compare the efficiency of the three probabilistic models. The results from the final model were presented as hazard and event time ratios. Our study comprised of 7,684 individuals, with an overall case fatality rate of 32.78%. Data suggested that older age, male sex, severe comorbidity score, intensive care unit admission, and invasive ventilation significantly increased risks for in-hospital mortality. Our study highlights the conditions that confer higher risks for adverse clinical outcomes attributed to COVID-19. The step-by-step process for selecting appropriate probabilistic models may be extended to other investigations in health research to provide more reliable evidence on this topic.

Interactive Effects of Obesity and Hypertension on Patterns of Hair Essential Trace Element and Mineral Content in Adult Women.

The objective of the present study was to evaluate potential similar patterns and interactive effects of obesity and hypertension on hair essential trace element and mineral content in adult women. In this cross-sectional study, a total of 607 adult women divided into controls (n = 101), groups with obesity without hypertension (n = 199), hypertension without obesity (n = 143), and both obesity and hypertension (n = 164) were included in the study. Assessment of hair mineral and trace element levels was performed by inductively-coupled plasma mass-spectrometry. Hair Ca, Mg, Co, and Mn levels in women with obesity, hypertension, and both diseases were significantly lower, compared to controls. Hair Mg levels in women with obesity and hypertension were significantly lower, whereas hair Na and K were found to be higher when compared to other groups. Hair Fe and V content in obese patients was lower than in other groups. Obesity was associated with lower hair Cu levels, whereas patients with hypertension had higher hair Cu content. Hypertension was also associated with higher hair Cr and Se content irrespective of body weight. Hair Zn levels in obese women with and without hypertension were significantly lower than those in healthy controls and normal-weight women with hypertension. In multiple regression models hair Mg was considered as a significant negative predictor of both systolic and diastolic blood pressure values. The observed alterations in hair trace element and mineral content provide an additional link between obesity and hypertension, although further detailed studies are required.

COVID-19 vaccination and case fatality rates: a case report in a Brazilian municipality / Vacinação contra a COVID-19 e taxas de letalidade: relato de caso em uma cidade brasileira / Vacunación contra el COVID-19 y tasas de letalidad: reporte de caso en una ciudad brasileña

Vaccination campaigns played a crucial role in reducing the incidence of COVID-19. However, a scant number of studies evaluated the impact of vaccination on case fatality rates (CFRs), including in Brazil. Our study aimed to compare CFRs according to vaccination status among subjects living in Arapongas (Paraná State, Brazil), considering the age composition of the population. Several strategies adopted by the Arapongas City Hall to minimize the spread of the virus were also elaborated upon. We accessed the 2021 database of the Arapongas Municipal Health Department, in which a total of 16,437 confirmed cases and 425 deaths were reported. The CFR was calculated as the ratio between COVID-19 deaths and the number of confirmed cases. Differences in age composition between unvaccinated and fully vaccinated individuals were observed in our study. Considering that CFR is a crude indicator and is highly sensitive to the age composition of the population, we adopted the average age distribution of confirmed cases among the three vaccination statuses (unvaccinated, partially, and fully) as a standard age distribution. The age-standardized CFR for unvaccinated and fully vaccinated groups were 4.55% and 2.42%, respectively. Fully vaccinated individuals showed lower age-specific CFRs in all age groups above 60 years than unvaccinated populations. Our findings strengthen the role of vaccination as a critical measure for preventing deaths among infected people and is particularly important to the ongoing reassessment of public health interventions and policies.

As campanhas de vacinação desempenharam um papel crucial na redução da incidência da COVID-19. No entanto, um número escasso de estudos avaliou o impacto da vacinação nas taxas de letalidade, inclusive no Brasil. Este estudo teve como objetivo comparar as taxas de letalidade de acordo com a situação vacinal dos residentes do Município de Arapongas (Paraná, Brasil), considerando a composição etária da população. Várias estratégias adotadas pela Prefeitura Municipal para minimizar a propagação do vírus também foram elaboradas. Acessou-se a base de dados de 2021 da Secretaria Municipal de Saúde de Arapongas, onde foram notificados 16.437 casos confirmados e 425 óbitos. A taxa de letalidade foi calculada como a razão entre as mortes por COVID-19 e o número de casos confirmados. Este estudo inédito observou diferenças na composição etária entre indivíduos não vacinados e totalmente vacinados. Considerando que a taxa de letalidade é um indicador bruto e altamente sensível à composição etária da população, adotou-se a distribuição etária média dos casos confirmados entre os três níveis vacinais (não vacinados, parcialmente vacinados e completamente vacinados) como distribuição etária padrão. A taxa de letalidade padronizada por idade para os não vacinados e completamente vacinados foi de 4,55% e 2,42%, respectivamente. Indivíduos completamente vacinados apresentaram menores taxas de letalidade específicas por idade em todas as faixas etárias acima de 60 anos em comparação às populações não vacinadas. Estes achados fortalecem o papel da vacinação como uma medida essencial para a prevenção de mortes entre pessoas infectadas e é de particular importância para a reavaliação contínua das intervenções e políticas de saúde pública.

Las campañas de vacunación juegan un papel clave en la reducción de la propagación del COVID-19. Sin embargo, pocos estudios evalúan el impacto de la vacunación en las tasas de letalidad, incluso en Brasil. Este estudio tuvo por objetivo comparar las tasas de letalidad según el estado de vacunación de los residentes de Arapongas (Paraná, Brasil) a partir de la composición por grupo de edad de la población. El Ayuntamiento Municipal aplicó varias estrategias para mitigar la propagación del virus. Se accedió a la base de datos de 2021 del Departamento de Salud de Arapongas, donde se reportaron 16.437 casos confirmados y 425 defunciones. Se calculó la tasa de letalidad como la relación entre las muertes por COVID-19 y el número de casos confirmados. Este estudio inédito evaluó las diferencias en la composición por grupo de edad entre individuos no vacunados y los individuos totalmente vacunados. Teniendo en cuenta que tasa de letalidad es un indicador bruto y muy sensible a la composición por grupo de edad de la población, se adoptó la distribución estándar por grupo de edad de los casos confirmados entre los tres niveles de vacunación (no vacunados, parcialmente vacunados y totalmente vacunados). La tasa de letalidad estandarizada por edad para los no vacunados y los totalmente vacunados fue del 4,55% y del 2,42%, respectivamente. Los individuos totalmente vacunados tenían más baja tasa de letalidad por grupo de edad en todos los grupos de edad superiores a los 60 años en comparación con las poblaciones no vacunadas. Estos hallazgos confirman el papel de la vacunación como una medida esencial de prevención de muertes entre los infectados y es importante para la reevaluación en curso de las intervenciones y políticas de salud pública.

Smoking is associated with altered serum and hair essential metal and metalloid levels in women.

The objective of the study was to evaluate the association between smoking and essential metal (Co, Cr, Cu, Fe, Mn, V, Zn) and metalloid (Se) levels in hair and serum of adult women using inductively coupled plasma-mass spectrometry (ICP-MS). In this cross-sectional study, a total of 344 women 20-70 years old including 199 smokers and 145 non-smoking women were enrolled. Serum Cu, Fe, and Zn levels in smoking women were found to be 6%, 8%, and 3% lower of levels in non-smokers, respectively. In contrast, circulating Mn, V, and especially Cr concentrations in smoking women exceeded the respective values in non-smoking women by 5%, 14%, and 54%. Hair Fe and Se levels in smoking women were 17% and 23% lower as compared to non-smoking controls, respectively. In multiple regression models, smoking severity was inversely associated with serum and hair Se concentrations, whereas the relationship to serum and hair Cr was positive. In addition, serum Zn and hair Fe levels were found to be inversely associated with the number of cigarettes per day. These findings hypothesize that health hazards of smoking may be at least in part be mediated by alteration in essential metal and metalloid metabolism.

Mercury and cancer: Where are we now after two decades of research?

The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.

The impact of COVID-19 vaccination on case fatality rates in a city in Southern Brazil.

BACKGROUND: Recent studies have established that vaccination plays a significant role in reducing COVID-19-related deaths. Here, we investigated differences in COVID-19 case fatality rates (CFRs) among vaccinated and unvaccinated populations, and analyzed whether the age composition of confirmed cases has a significant effect on the variations in the observed CFRs across these groups. METHODS: The study considered 59,853 confirmed cases and 1,687 deaths from COVID-19, reported between January 1 to October 20, 2021, by the Health Department of Londrina, a city in Southern Brazil. We used Negative Binomial regression models to estimate CFRs according to vaccination status and age range. RESULTS: There are significant differences between the CFR for fully vaccinated and unvaccinated populations (IRR = 0.596, 95% CI [0.460 - 0.772], P < .001). Vaccinated populations experience fatality rates 40.4% lower than non-vaccinated. In addition, the age composition of confirmed cases explains more than two-thirds of the variation in the CFR between these 2 groups. CONCLUSIONS: Our novel findings reinforce the importance of vaccination as an essential public health measure for reducing COVID-19 fatality rates in all age groups. The results also provide means for accurately assessing differences in CFRs across vaccinated and unvaccinated populations. Such assessment is essential to inform and determine appropriate containment and mitigation interventions in Brazil and elsewhere.

Meteorological parameters and cases of COVID-19 in Brazilian cities: an observational study.

Meteorological parameters modulate transmission of the SARS-Cov-2 virus, the causative agent related to coronavirus disease-2019 (COVID-19) development. However, findings across the globe have been inconsistent attributed to several confounding factors. The aim of the present study was to investigate the relationship between reported meteorological parameters from July 1 to October 31, 2020, and the number of confirmed COVID-19 cases in 4 Brazilian cities: São Paulo, the largest city with the highest number of cases in Brazil, and the cities with greater number of cases in the state of Parana during the study period (Curitiba, Londrina and Maringa). The assessment of meteorological factors with confirmed COVID-19 cases included atmospheric pressure, temperature, relative humidity, wind speed, solar irradiation, sunlight, dew point temperature, and total precipitation. The 7- and 15-day moving averages of confirmed COVID-19 cases were obtained for each city. Pearson's correlation coefficients showed significant correlations between COVID-19 cases and all meteorological parameters, except for total precipitation, with the strongest correlation with maximum wind speed (0.717, <0.001) in São Paulo. Regression tree analysis demonstrated that the largest number of confirmed COVID-19 cases was associated with wind speed (between ≥0.3381 and <1.173 m/s), atmospheric pressure (<930.5mb), and solar radiation (<17.98e+3). Lower number of cases was observed for wind speed <0.3381 m/s and temperature <23.86°C. Our results encourage the use of meteorological information as a critical component in future risk assessment models.

BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity.

BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice (B6) and DBA/2J mice (D2), which through meiotic recombination events possesses recombinant chromosomes containing B6 or D2 haplotype segments. The quantitative trait loci (QTLs) are the locations of segregating genetic polymorphisms and are fundamental to understanding genetic diversity in human disease susceptibility and severity. QTL mapping represents the typical approach for identifying naturally occurring polymorphisms that influence complex phenotypes. In this process, genotypic values at markers of known genomic locations are associated with phenotypic values measured in a segregating population. Indeed, BXD RI strains provide a powerful tool to study neurotoxicity induced by different substances. In this review, we describe the use of BXD RI lines to understand the underlying mechanisms of neurotoxicity in response to ethanol and cocaine, as well as metals and pesticide exposures.

Risk factors associated with COVID-19-induced death in patients hospitalized in intensive care units (ICUs) in a city in Southern Brazil.

OBJECTIVES: The aim of this research was to address risk factors associated with death after hospitalization in intensive care units (ICUs) in 728 COVID-19 patients in Londrina, the second most populated city in the State of Paraná - Brazil, between March and December 2020. METHODS: Statistical analysis, including multiple logistic regression was performed to identify risk factors associated with death in these patients. RESULTS: The results showed that age (60 years or more, O.R. = 3.13, C.I. 95% [2.02; 4.84]), days in the ICU (11 days or more, O.R. = 1.76, C.I. 95% [1.16; 2.66]), neurological diseases (O.R. = 2.15, C.I. 95% [1.07; 4.31]), pneumopathy (O.R = 2.19, C.I. 95% [1.01; 4.82]), diabetes (O.R. = 1.55, C.I. 95% [1.03; 2.32]), and kidney disease (O.R. = 2.27, C.I. 95% [1.18; 4.70]) were associated with increased risk for death from COVID-19. CONCLUSION: Knowing the risk factors associated with death after ICUs hospitalization is useful for identifying the most vulnerable groups, as well as for defining vaccination priorities, considering its scarcity in many parts of the world, mainly in underdeveloped countries, including Brazil.

Hair Lead, Aluminum, and Other Toxic Metals in Normal-Weight and Obese Patients with Coronary Heart Disease.

The objective of the present study was to evaluate hair toxic metal levels in patients with obesity and/or coronary heart disease (CHD). Following a 2 × 2 factorial design, subjects without CHD were grouped into normal weight control (n = 123) and obese groups (n = 140). Patients suffering from CHD were divided into normal weight (n = 180) and obese CHD subjects (n = 240). Hair Al, As, Cd, Hg, Ni, and Pb levels were evaluated using inductively-coupled plasma mass-spectrometry. The data demonstrate that hair Al and Hg levels were higher in obese subjects as compared to normal weight controls. Normal weight CHD patients were characterized by significantly higher hair Al, As, Cd, and Pb levels when compared to healthy subjects. The highest hair Al, As, and Pb levels were observed in obese CHD patients, significantly exceeding the respective values in other groups. Factorial analysis revealed significant influence of factorial interaction (CHD*obesity) only for hair Pb content. Given the role of obesity as a risk factor for CHD, it is proposed that increased toxic metal accumulation in obesity may promote further development of cardiovascular diseases.

Environmental and health hazards of military metal pollution.

An increasing body of literature has demonstrated that armed conflicts and military activity may contribute to environmental pollution with metals, although the existing data are inconsistent. Therefore, in this paper, we discuss potential sources of military-related metal emissions, environmental metal contamination, as well as routes of metal exposure and their health hazards in relation to military activities. Emission of metals into the environment upon military activity occurs from weapon residues containing high levels of particles containing lead (Pb; leaded ammunition), copper (Cu; unleaded), and depleted uranium (DU). As a consequence, military activity results in soil contamination with Pb and Cu, as well as other metals including Cd, Sb, Cr, Ni, Zn, with subsequent metal translocation to water, thus increasing the risk of human exposure. Biomonitoring studies have demonstrated increased accumulation of metals in plants, invertebrates, and vertebrate species (fish, birds, mammals). Correspondingly, military activity is associated with human metal exposure that results from inhalation or ingestion of released particles, as well as injuries with subsequent metal release from embedded fragments. It is also notable that local metal accumulation following military injury may occur even without detectable fragments. Nonetheless, data on health effects of military-related metal exposures have yet to be systematized. The existing data demonstrate adverse neurological, cardiovascular, and reproductive outcomes in exposed military personnel. Moreover, military-related metal exposures also result in adverse neurodevelopmental outcome in children living within adulterated territories. Experimental in vivo and in vitro studies also demonstrated toxic effects of specific metals as well as widely used metal alloys, although laboratory data report much wider spectrum of adverse effects as compared to epidemiological studies. Therefore, further epidemiological, biomonitoring and laboratory studies are required to better characterize military-related metal exposures and their underlying mechanisms of their adverse toxic effects.

Review of the mechanism underlying mefloquine-induced neurotoxicity.

Mefloquine, a potent blood schizontocide, is effective against drug-resistant Plasmodium falciparum. This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects). The mechanisms that underlie the neurological/psychiatric complications of mefloquine are poorly understood. The aim of this study was to review the literature on the neurotoxic mechanisms of action of mefloquine to better understand its potential toxicity in the central nervous system, highlighting the mechanisms that lead to its psychiatric disorders. Experimental studies on the neurotoxic effects of mefloquine discussed herein include brain transporters of mefloquine, alteration in neurotransmitters, disruption on calcium (Ca2+) homeostasis and neuroinflammation, generation of oxidative stress response in neurons (involving glutathione, increased F2-isoprostanes, accumulation of cytosolic lipid globules), and alteration of voltage-dependent channels, as well as gap junction intercellular communications. Although several hypotheses have been proposed for the mechanisms that mediate mefloquine-induced brain damage, they are not fully understood, necessitating additional studies in the future.

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

An updated systematic review on the association between Cd exposure, blood pressure and hypertension.

BACKGROUND: Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent. OBJECTIVE: The aim of this study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020. METHODS: We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design. RESULTS: Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers. CONCLUSIONS: A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.

Endothelial Dysfunction Induced by Cadmium and Mercury and its Relationship to Hypertension.

Hypertension is an important public health concern that affects millions globally, leading to a large number of morbidities and fatalities. The etiology of hypertension is complex and multifactorial, and it involves environmental factors, including heavy metals. Cadmium and mercury are toxic elements commonly found in the environment, contributing to hypertension. We aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development of hypertension. A narrative review was carried out through database searches. In this review, we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provided new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction. Although the mechanisms by which cadmium and mercury induce hypertension have yet to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive etiology.

Social injustice in environmental health: A call for fortitude.

The objective of this short paper is to call upon the scientific community to channel its attention to the duty and heedfulness of social justice issues. While recognized for decades the impact of social injustice on public health and its disproportionate effects on poorer communities, little has been done to systematically address it. Here, we provide several examples pertinent to the health outcomes associated with social injustice and call upon the scientific community to attend to the issue and antagonize those who attempt to subvert science and its role in ensuring social justice in health.