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Cholangiocarcinoma (CCA) is a malignancy that originates from the epithelial cells of the biliary system. Despite advancements in medical diagnostic techniques, CCAs remain a challenge to detect due to their silent clinical progression, making it difficult to diagnose these diseases. There are several well-established risk factors for CCA, including biliary tract infection and inflammation. However, there is also growing evidence that community and occupational exposures play a significant role in the development of bile duct cancers. This review examines the geographical distribution of these risk factors and the importance of surveillance in individuals exposed to these toxins who are more prone to developing CCA.

BackgroundDaycare and school closures prompted by shelter-in-place orders may have increased opportunities for unintentional ingestions among young children.ObjectivesWe examined emergency department (ED) presentations for toxic exposures among young children during the COVID-19 pandemic in the San Francisco Bay Area, which had some of the strictest and most prolonged shelter-in-place policies in the United States.MethodsWe performed a retrospective cross-sectional study of children 0 to 5 years of age who presented with an ED International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis code of toxic exposure within a tertiary care hospital system between March 16, 2016 and March 15, 2021. We considered the period after March 16, 2020 to represent the pandemic.ResultsDuring the pandemic, the absolute number of poisonings among young children remained stable. Overall, ED encounters within this cohort decreased by 55%, which doubled the relative toxic exposure rate per 1000 ED encounters from 4.99 (95% confidence interval [CI] 3.19-5.90) to 9.79 (95% CI 8.09-11.49). Rates of admission, severe medical complications, operating room case requests, and length of stay were not significantly different. Shelter-in-place was associated with significantly higher odds of cannabis ingestion (odds ratio = 2.70, 95% CI 1.60-4.49).ConclusionDespite dramatic decreases in overall ED patient volumes, the absolute number and severity of toxic exposures were similar during the pandemic compared with previous years. © 2022 Elsevier Inc.

Armed conflicts result in the release of toxic chemicals into the surrounding environment and civilians are commonly exposed to these toxicants. This paper reviews the evidence on civilian exposure to toxic chemicals, including but not limited to inhaled toxic substances, in post-World War II armed conflicts, and proposes a framework for the implementation of long-term surveillance programs for these populations. Four databases of peer-reviewed health articles were searched for all English-language articles with a primary focus on toxic chemical exposures among civilians in armed conflicts since World War II. The review was supplemented substantially by the gray literature. In the 66 articles that met the inclusion criteria, the authors categorized the chemical toxicants to which civilians have been exposed in modern armed conflicts as ubiquitous (e.g. smoke, dust, and munitions components present in all conflicts) or particular agents (e.g. specific chemical agents used in a few conflicts). While most studies focused on particular agents, the vast majority of civilians are in fact exposed to ubiquitous agents both in the acute conflict phase and through persistent environmental exposures after the cessation of hostilities. There is a dearth of research concerning civilian exposures to toxic chemicals during armed conflicts. In line with principles of equity, justice, and accountability, robust research and surveillance programs are urgently needed to document exposures and provide ongoing assessments and any necessary treatment for these long-ignored populations, most of whom live in the Global South. [ABSTRACT FROM AUTHOR]

Abstract Background Environmental health research in the US has shown that racial and ethnic minorities and members of low-socioeconomic groups, are disproportionately burdened by harmful environmental exposures, in their homes, workplace, and neighborhood environments that impact their overall health and well-being. Systemic racism is a fundamental cause of these disproportionate exposures and associated health effects. To invigorate and inform current efforts on environmental justice and to raise awareness of environmental racism, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop where community leaders, academic researchers, and NIEHS staff shared perspectives and discussed ways to inform future work to address health disparities. Objectives To share best practices learned and experienced in partnerships between academic researchers and communities that are addressing environmental racism across the US; and to outline critical needs and future actions for NIEHS, other federal agencies, and anyone who is interested in conducting or funding research that addresses environmental racism and advances health equity for all communities. Discussion Through this workshop with community leaders and researchers funded by NIEHS, we learned that partnerships between academics and communities hold great promise for addressing environmental racism; however, there are still profound obstacles. To overcome these barriers, translation of research into plain language and health-protective interventions is needed. Structural changes are also needed in current funding mechanisms and training programs across federal agencies. We also learned the importance of leveraging advances in technology to develop creative solutions that can protect public health.

The passage of the PACT Act of 2022 expanded the services veterans receive through the U.S. Department of Veterans Affairs (VA), ensuring they now qualify for benefits if they’ve been exposed to certain toxins during their military service. This significant expansion of VA benefits also highlights the need for nurses and other health providers working outside the VA system—who care for millions of veterans—to be well-informed about their patients’ military experiences and any potential environmental exposures and health impacts. In this article, the author raises awareness of military environmental exposures and offers guidance about exposure-informed care. [ABSTRACT FROM AUTHOR]

Abstract Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery.

Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery. [ABSTRACT FROM AUTHOR]

Introduction: Between early March 2020 and the end of May 2020, Italy issued strict measures to limit further spread of coronavirus disease 2019 (COVID-19) and became the first European country that imposed a lockdown on the population. The aim of this study was to assess the impact of these restricted conditions on the activity of the Poison Control Center (PCC) of Policlinico Umberto I Hospital-Sapienza University of Rome. Methods: This was a retrospective analysis of calls received by the PCC during the lockdown period March 9, 2020 through May 31, 2020 compared to the same time period in year 2019 (reference). Results: We observed a reduction in calls from hospitals and emergency departments and an increase in calls from private citizens about exposures to products or intoxications during the lockdown. There were increases in unintentional exposures and exposures to hand and surface sanitizers among household and cleaning products. There was a decrease in calls concerning medications, which were mostly from hospitals and emergency departments. We observed increases in exposures requiring clinical observations among adults and referral to the emergency department among pre-school children. Conclusions: Public health protection measures against COVID-19 to improve hygiene and maintain clean environments can increase exposures to hazardous products in the domestic environment. We observed an increase in unintentional exposures to household and cleaning products during the lockdown and an increase in ED referrals for pre-school children compared to the previous year. Our data suggest the need for improvements in public campaigns that promote safer handling of household products and prevent unnecessary exposures during a lockdown. The public health promotion activity can benefit the community after the pandemic and prepare the community for lockdowns in the future. [ABSTRACT FROM AUTHOR]

Objective: To describe conjugal multiple system atrophy (MSA) in a couple married for 44 years, and to report environmental risk factors possibly contributing to the occurrence.Methods: Case description of conjugal MSA with report of shared environmental risk factors and retrospective review of consecutively diagnosed MSA patients between 1998 and 2012 with autonomic reflex screen at Mayo Clinic, Rochester (clinical series). Probability calculation was based on the age-specific point prevalence of MSA.Results: A husband and wife both developed MSA symptoms at age 63. The husband's onset was of imbalance, followed by falls and genitourinary failure; parkinsonism and antecollis was evident on examination. Autonomic testing showed widespread autonomic failure. The patient died 2.25 years after onset. The wife initially developed urinary symptoms progressing to incontinence. Parkinsonism, dysphonia, and falls began within 1 year. Autonomic testing revealed severe autonomic failure. Interview with the surviving wife and son revealed substantial chemical exposure, in particular pesticides. In our clinical series, there were no other cases of conjugal MSA. Assuming an age-specific point prevalence of MSA based on population studies and independence of the two events, the probability of both individuals developing MSA by chance is 6.08 e-9.Conclusion: Based on the population point prevalence of MSA, conjugal MSA is rare but possible. We conclude that this case of conjugal MSA likely occurred by chance; however, exposure to shared risk factors (pesticides) may be contributory. Because this is the first reported case of conjugal MSA, to our best knowledge, evidence for transmissibility between spouses is lacking. [ABSTRACT FROM AUTHOR]

Anthropology has largely ignored plastics, even as they have emerged as the paradigmatic material-and problem-of our times. In this article, we make the case for an anthropology of plastics as a priority for environmental and medical anthropological research. Drawing from exploratory fieldwork in India, we briefly highlight the benefits and risks of different types of plastics, identify areas for anthropological investigations of human-plastic entanglements, and unpack major debates about plastic control. We recommend analyses that take into account the social life of plastics and the life cycle of plastic production, consumption, circulation, disposal, retrieval, and decomposition. We propose a facilitator role for anthropologists in bringing environmental NGOs and the plastic industry to the table to reduce the human and environmental health risks related to widespread reliance on plastics. Overall, we argue that anthropological analyses are urgently needed to address environmental and global health concerns related to plastics. [ABSTRACT FROM AUTHOR]

The issue of pregnant women’s exposures to everyday chemicals and the implications for the health of future children are receiving increased attention in popular media and in the academic press. In response, health profession organizations are developing clinical practice guidelines for warning pregnant women about the risks associated with exposures to certain toxics. We evaluate different sides of a risk-avoidance approach for pregnant women in the context of a hypothetical case study involving phthalates and women who work in nail salons. We consider the ubiquitous nature of low-dose exposures and both the positive aspects and limitations of promoting avoidance measures with respect to phthalate exposures. We conclude that a risk-disclosure approach has both practical limitations and equity dimensions which must be factored in to public health guidelines and messaging and the development of clinical practice guidelines. Upstream solutions including regulatory action on chemicals and heightened attention to environmental justice would result in optimal management of this issue. [ABSTRACT FROM AUTHOR]

Many of the United States' more than 18 million veterans obtain healthcare through the Department of Veterans Affairs' (VA) Veterans Health Administration system; however, recent legislative changes have expanded veterans' access to non-VA care in their communities, particularly for those who do not live near VA medical centers. Veterans are seen by physicians in outpatient practice across the United States and are admitted to non-VA hospitals; this is particularly salient for older veterans, who may require a more frequent and high level of care. We present a review of characteristics of U.S. veterans from two conflicts: World War II (WWII) and the Korean War. While non-VA clinicians are well equipped to provide care for patients of all different ages, veterans of armed conflicts have a unique constellation of exposures and cultural considerations that must be accounted for when providing them care. In this review, we describe characteristics of the generations of American veterans who served in WWII and the Korean War conflicts in a brief historical context. We then note conflict-specific exposures and potential long-term sequelae to watch for during physical examinations and to monitor thereafter, age-specific health and emotional concerns, and best practices for providing care to this cohort of veterans., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Akwe et al.)

Multiple trace elements have estrogen receptor activity, but the association of these elements with uterine leiomyoma has not been defined. A cohort of 473 women aged 18–44 undergoing surgery for benign gynecologic indications provided whole blood and urine specimens for trace element analysis, which was performed by inductively coupled plasma mass spectrometry. Twenty elements were analyzed in blood and 3 in urine. The surgeon documented whether fibroids were present. Geometric mean concentrations were compared between women with and without fibroids, and logistic regression models were generated to assess the impact of the concentration of each trace element on the odds of fibroids. In multivariate regressions, odds of a fibroid diagnosis were higher with increased whole blood cadmium (AOR 1.44, 95% CI 1.02, 2.04) and lead (AOR 1.31 95% CI 1.02, 1.69), and urine cobalt (AOR 1.31, 95% CI 1.02, 1.70). Urinary cadmium and lead were not related to fibroid diagnosis. Increased exposure to trace elements may contribute to fibroid growth, and fibroids may serve as a reservoir for these elements. Differences between urinary and whole blood findings merit further investigation, as urinary cadmium has been considered a superior marker of exposure. [ABSTRACT FROM AUTHOR]

Social Determinants of Health (SDOH) consider social, political, and economic factors that contribute to health disparities in patients and populations. The most common health-related SDOH exposures are food and housing insecurity, financial instability, transportation needs, low levels of education, and psychosocial stress. These domains describe risks that can impact health outcomes more than health care. Epidemiologic and translational research demonstrates that SDOH factors represent exposures that predict harm and impact the health of individuals. International and national guidelines urge health professionals to address SDOH in clinical practice and public health. The further implementation of these recommendations into basic and translational research, however, is lagging. Herein, we consider a precision health framework to describe how SDOH contributes to the exposome and exacerbates physiologic pathways that lead to chronic disease. SDOH factors are associated with various forms of stressors that impact physiological processes through epigenetic, inflammatory, and redox regulation. Many SDOH exposures may add to or potentiate the pathologic effects of additional environmental exposures. This overview aims to inform basic life science and translational researchers about SDOH exposures that can confound associations between classic biomedical determinants of disease and health outcomes. To advance the study of toxicology through either qualitative or quantitative assessment of exposures to chemical and biological substances, a more complete environmental evaluation should include SDOH exposures. We discuss common approaches to measure SDOH factors at individual and population levels and review the associations between SDOH risk factors and physiologic mechanisms that influence chronic disease. We provide clinical and policy-based motivation to encourage researchers to consider the impact of SDOH exposures on study results and data interpretation. With valid measures of SDOH factors incorporated into study design and analyses, future toxicological research may contribute to an evidence base that can better inform prevention and treatment options, to improve equitable clinical care and population health. © 2022 Wiley Periodicals LLC., (© 2022 Wiley Periodicals LLC.)

The dramatic increase in prevalence rates of Autism Spectrum Disorders (ASDs) over recent decades likely reflects the influence of multiple factors. In the current paper, it is argued ASDs can result from an interaction between genetic susceptibilities and environmental exposures. Specifically, we hypothesize that fetal or infantile exposure to methyl mercury containing pollution by individuals with biologically inhibited antioxidant functions contributes to development of autism. Correlational data reveal that ASD rates are higher in areas of greater pollution levels, and autistic individuals exhibit biological evidence of mercury toxicity. Further, oxidative stress and decreased antioxidant activities are manifested in individuals with ASDs, specifically autism. Taken together, available evidence supports a methyl mercury-induced oxidative stress model of the disorders for at least some sufferers. Consequently, legislative efforts should focus on preventing exposures to methyl mercury and other toxicants that can adversely impact neurodevelopment. [ABSTRACT FROM AUTHOR]

Introduction. Poisoning is a common cause of emergency visits and hospital admission in Western countries. The purpose of this study was to assess the incidence and type of toxic exposures presenting to emergency medical facilities in Iceland. Materials and methods. The study was prospective and included all patients with confirmed or suspected poisoning presenting to hospitals and rural medical centers providing emergency services in Iceland during the twelve-month period from April 2001 until March 2002. Results. A total of 1,121 toxic exposures were documented representing an incidence of 3.91 cases per 1,000 inhabitants per year. The female to male ratio was 1.23. The majority of exposures (56.7%) occurred in the patient's home, 60% were deliberate, 72% had drugs and/or alcohol as their main cause, and 11% involved illicit drugs. Exposures to chemicals other than drugs were usually unintentional. Conclusion. Toxic exposures requiring emergency medical care are common in Iceland. Self-poisonings by ingestion of prescription drugs and/or alcohol accounted for the majority of cases. [ABSTRACT FROM AUTHOR]

Abstract: Persons heterozygous for Z, S and rare alpha-1-antitrypsin (AAT, SERPIN1A) polymorphisms (ca. 9% of population) are often considered ‘silent’ carriers with increased vulnerability to environmentally modulated liver and lung disease. They may have significantly more anxiety and bipolar spectrum disorders, nutritional compromise, and white matter disease [Schmechel DE, Browndyke J, Ghio A. Strategies for the dissection of genetic–environmental interactions in neurodegenerative disorders. Neurotoxicology 2006;27:637–57]. Given association of art and mood disorders, we examined occupation and artistic vocation from this same series. One thousand five hundred and thirty-seven consecutive persons aged 16–90 years old received comprehensive work-up including testing for AAT ‘phenotype’ and level, nutritional factors, and inflammatory, iron and copper indices. Occupations were grouped by Bureau of Labor Standards classification and information gathered on artistic activities. Proportion of reactive airway disease, obstructive pulmonary disease, and pre-existing anxiety disorder or bipolar disorder were significantly increased in persons carrying AAT non-M polymorphisms compared to normal MM genotype (respectively, 10, 20, 21, and 33% compared to 8, 12, 11, and 9%; contingency table, pulmonary: χ 2 =37, p =0.0001; affective disorder: χ 2 =171, p =0.0001). In persons with artistic avocation (n =189) or occupation (n =57), AAT non-M polymorphisms are significantly increased (respectively, proportions of 44 and 40% compared to background rate of 9%; contingency table, avocation: χ 2 =172, p =0.0001; occupation: χ 2 =57, p =0.0007). Artistic ability and ‘anxiety/bipolar spectrum’ mood disorders may represent phenotypic attributes that had selective advantage during recent human evolution, an ‘intensive creative energy’ (ICE) behavioral phenotype. Background proportion of ICE of 7% consists of 49 of 1312 persons with AAT MM genotype (4%), and 58 of 225 persons with non-MM genotypes (26%) (contingency table, χ 2 =222, p =0.0001). Penetrance of ICE increases in genotypes with lower AAT levels: PiMS, 18%; PiMZ, 44%; PiSS and PiZZ, 100% (five cases). At all ages, persons with non-MM genotype had significantly higher proportion of thiamine deficiency (50% in PiMZ), reactive hypoglycemia (20% in PiMZ), and possibly fatty liver (thiamine: χ 2 =28, p =0.0001; hypoglycemia: χ 2 =92, p =0.0001). In older persons, PiMZ genotype had significantly increased proportion (46%) of brain MRI T2 white matter abnormalities (χ 2 =49, p =0.003). Persons with ICE and MM genotype showed increased prevalence of pulmonary disorders and same signature as S and Z carriers and homozygotes (see above). Z polymorphism was associated with delayed age of onset (average 7 years) for persons with toxic environmental or occupational exposures (log rank, p =0.0001) and more stable cognitive change in persons with neurodegenerative illness (p <0.05). At all ages, ICE phenotype and Z polymorphism were associated with altered copper homeostasis with low or absent non-ceruloplasmin bound copper (p <0.05). AAT polymorphisms which affect iron, lipid and copper metabolism may affect early events in nervous system development, function and response to environmental exposures. AAT may also be a ‘switch’ for copper metabolism and low ‘free’ copper would be theorized to provide protection for lipid oxidation and favorably affect beta-amyloid and other aggregation, but possibly alter early ‘critical’ period of CNS development. AAT polymorphisms may define an important and treatable subset of persons presenting with CNS disorders. This new proposed phenotype for AAT transcends classic pattern of strictly liver and lung disease, and should be considered for proper evaluation and management of patients presenting with classic AAT-related disorders, affective disorders, persons with ICE, white matter disease or multisystem disorders of memory. [Copyright &y& Elsevier]

Background: Buprenorphine prescriptions have increased dramatically within the United States, whereas methadone continues to be used widely. We investigated the trends and characteristics of buprenorphine and methadone exposures in the pediatric population.Methods: We identified pediatric exposures to buprenorphine and methadone using the National Poison Data System from 2013 to 2016. We descriptively assessed characteristics of the exposures. Trends in exposures were evaluated using generalized linear mixed models.Results: Pediatric buprenorphine exposures increased from 2013 (1097) to 2016 (1226) while methadone calls decreased (486 to 396). After adjusting for the random effects of the geographical region, the mean number of pediatric buprenorphine exposures (per 100,000 pediatric population) increased from 1.3 to 1.5 (P = .05). Conversely, the mean number of methadone exposures decreased from 0.6 to 0.4 (P = .03). Children aged ≤3 years constituted the highest percentage of both exposures. Unintentional exposures accounted for most of the buprenorphine (86.9%) and methadone (62.4%) exposures. Major clinical effects were demonstrated in 2.3% of buprenorphine exposures and were more frequent with methadone (13%). West Virginia and Maryland demonstrated the highest incidence of buprenorphine and methadone exposures, respectively.Conclusions: Pediatric buprenorphine exposures increased but demonstrated less severe effects compared to methadone exposures, which decreased during the study period. [ABSTRACT FROM AUTHOR]

During their deployment to Iraq in support of Operation Iraqi Freedom (OIF) , many Veterans were exposed to a wide array of toxic substances and psychologic stressors, most notably airborne/environmental pollutants from open burn pits. Service members do not deploy whilst unhealthy, but often they return with a multitude of acute and chronic symptoms, some of which only begin to manifest years after their deployment. Our findings, while preliminary in nature, suggest that Iraq War Veterans who participated in our survey reported a decrease in overall physical fitness and increased respiratory clinical symptoms compared with pre-deployment periods. The objective of this report is to provide information that will benefit how combat Veterans are cared for post-deployment. Strategies for a wider and more comprehensive assessment and medical screening process post-deployment are recommended.

Our genetic makeup and environment interact. Evidence has emerged demonstrating preconception and prenatal exposure to toxic agents have a profound effect on reproductive health. We cannot change our genetics, but we can change our environment. Health providers can protect pregnancies from harmful exposures. Pregnancy is the most critical time-window for human development, when any toxic exposure can cause lasting damage to brain development. Reproductive care professionals can provide useful information to patients and refer patients to appropriate specialists when hazardous exposure is identified. Clinical experience and expertise in communicating risks of treatment are transferable to environmental health., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The issue of pregnant women's exposures to everyday chemicals and the implications for the health of future children are receiving increased attention in popular media and in the academic press. In response, health profession organizations are developing clinical practice guidelines for warning pregnant women about the risks associated with exposures to certain toxics. We evaluate different sides of a risk-avoidance approach for pregnant women in the context of a hypothetical case study involving phthalates and women who work in nail salons. We consider the ubiquitous nature of low-dose exposures and both the positive aspects and limitations of promoting avoidance measures with respect to phthalate exposures. We conclude that a risk-disclosure approach has both practical limitations and equity dimensions which must be factored in to public health guidelines and messaging and the development of clinical practice guidelines. Upstream solutions including regulatory action on chemicals and heightened attention to environmental justice would result in optimal management of this issue.