Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe

Introduction

The NBOMes (N-benzyl-oxy-methyl derivatives of known 2C phenylethylamines) are a new and growing class of potent synthetic stimulants. Case reports provide the bulk of available safety and clinical data for clinicians. We report two cases of NBOMe intoxication with 25C-NBOMe (the first lab-confirmed US case) and 25B-NBOMe, respectively, both confirmed via triple quadrapole mass spectrometry.

Case Reports

Case 1: A 16-year-old girl had a generalized seizure after reported use of 25I-NBOMe. She presented with altered mental status, lower extremity rigidity, and elevated CPK (6042 U/L). Despite treatment with benzodiazepines, her lower extremity rigidity persisted and CPK peaked at 47,906 U/L. She was discharged on hospital day 8. Serum and urine specimens confirmed presence of 25C-NBOMe. Case 2: A 15-year-old boy developed bizarre behavior after reported use of 25I-NBOMe. In the ED, he had two generalized seizures and persistent muscle rigidity. CPK peaked at 429 U/L. Seizures were managed with benzodiazepines, and he was discharged within 24 h. Serum specimens revealed 25B-NBOMe.

Discussion

NBOMes are amphetamine derivatives and highly potent 5-HT_2A receptor agonists. Clinical manifestations are a product of enhanced central sympathetic and serotonergic tone. We report two cases of NBOMe intoxication in patients who believed they used 25I-NBOME, while lab confirmation proved otherwise. Whether unique clinical manifestations are specific to the NBOMe variant, dose, route of administration, or other factors is unknown. Laboratory confirmation may play a role in identifying unexpected NBOMe variants, while contributing to the epidemiologic data on these novel substances.     

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.     

Genetic variants of coagulation factor XIII,postmenopausal estrogen therapy,and risk of nonfatal myocardial infarction

We hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction =.03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy.     

Household Crowding and Food Insecurity Among Inuit Families With School-Aged Children in the Canadian Arctic

Objectives. We examined the relation of household crowding to food insecurity among Inuit families with school-aged children in Arctic Quebec.Methods. We analyzed data collected between October 2005 and February 2010 from 292 primary caregiver–child dyads from 14 Inuit communities. We collected information about household conditions, food security, and family socioeconomic characteristics by interviews. We used logistic regression models to examine the association between household crowding and food insecurity.Results. Nearly 62% of Inuit families in the Canadian Arctic resided in more crowded households, placing them at risk for food insecurity. About 27% of the families reported reducing the size of their children’s meals because of lack of money. The likelihood of reducing the size of children’s meals was greater in crowded households (odds ratio = 3.73; 95% confidence interval = 1.96, 7.12). After we adjusted for different socioeconomic characteristics, results remained statistically significant.Conclusions. Interventions operating across different levels (community, regional, national) are needed to ensure food security in the region. Targeting families living in crowded conditions as part of social and public health policies aiming to reduce food insecurity in the Arctic could be beneficial.Inadequate housing conditions (e.g., crowding and structural damage) are prevalent among First Nations and Inuit communities in Canada and elsewhere.1 In Nunavik, the Inuit homeland in Arctic Quebec, Canada, the government promoted the relocation of many Inuit families to fledgling communities during the 1950s. Relocated families were moved to small, poorly heated and insulated accommodations. Since then, different programs have been designed by the federal, provincial, territorial, and regional governments to address the housing problem in Nunavik and across the Canadian Arctic.2 At present, more than 90% of the Nunavik population has reported living in social (subsidized) housing.3 In this region, social housing units are allocated locally through a point-based system set according to specific criteria, so that applicants most in need are given first priority (e.g., families with lower income, with young children, and living in overcrowded dwellings).2 Rent is set according to household income, while also considering the cost of living.4 Thus, in Nunavik, housing tenure does not differentiate between households on the basis of financial security or income level, given that nearly all of the population resides in social housing. Such organization rather highlights the high degree of financial need throughout this population and a limited private residential market unattainable by most of the population.Household overcrowding, generally defined as more than 1 person per room,5 is particularly problematic in Nunavik. According to Statistics Canada, 49% of the 2006 population lived in overcrowded houses.5 Often, overcrowding is approached as a consequence of economic difficulties. Living in smaller homes or in shared accommodation has been known as a way to lower living costs to dedicate the available financial resources to other basic necessities.6 In such situations, overcrowded households may experience higher food insecurity as a result of a precarious economic situation. In the particular case of Nunavik, however, crowding is a direct consequence of an underlying, and persistent, lack of housing. Household crowding in Nunavik is not only a product of financial difficulties but also an effect of the rapidly growing and young population. Between 2001 and 2006, the population in Nunavik increased by 12% compared with 4% for the province of Quebec. During the past 3 decades, the population has doubled from 5860 in 1986 to 12 090 in 2011.7 In 2008, it was estimated that more than 900 new housing units were needed, but only 239 units were constructed.8 The housing backlog is further compounded by high costs of construction and short building seasons.The housing situation in Nunavik and throughout the Canadian Arctic raises concerns, in terms of both public health and the health of each individual resident, especially that of children.9–14 Indeed, studies have shown that household crowding is associated with poorer respiratory health, especially among children.12,15 In crowded dwellings, the lack of privacy and the difficulty of withdrawing from (unwanted) social interactions may limit the ability of controlling one’s home situation and lead to “overarousal.”16 Household crowding also has been identified as eliciting chronic stress responses in adults,17 anger and depression18 with possible repercussions on behaviors,19–22 withdrawal,23 and reduced social support24 that, we contend, could influence household food insecurity.Food insecurity occurs when it is not possible to obtain safe, sufficient, and nutritiously adequate foods for a healthy life in socially and culturally acceptable ways.25–27 Studies have shown that in a situation of food insecurity, adults generally first reduce their own food consumption. As the situation becomes more severe, children’s diets also will be reduced, particularly in low-income households with single mothers.28,29 In 2012, 14% of the households in Canada experienced food insecurity.30 In Canadian Arctic communities, food insecurity is high: 62.2% and 31.6% of children live in food-insecure households in Nunavut and Northwest Territories, respectively.30 In Nunavik, the proportion of Inuit children experiencing food insecurity reached 30% in 2006.31 Studies emphasize that a reduction of the quality in diet and nutrient intake resulting from food insecurity is linked to various health issues in children, including poor health,25,32–34 developmental delays,35 and poor mental health.36Access to food products supplied from southern regions of Quebec comes at a very high cost to Nunavik, with an average price 57% higher than in the provincial capital.37 Despite efforts to redress this situation, food costs remain very high and often inaccessible to many Nunavik families who must resort to reducing the amount of food supplies or buying products of lower nutritional quality,38 which compromises health and well-being.36,37,39In a study conducted among low-income families in the United States, Cutts et al.40 found a higher risk of food insecurity and child food insecurity in households with higher housing insecurity. In their study, crowding and multiple moves were considered as indicators of housing insecurity. This association was independent of maternal and family characteristics such as education and household employment. In a recent study involving Inuit households from Nunavut, in the eastern Canadian Arctic, Huet et al.41 reported higher food insecurity among Inuit living in overcrowded households and in houses requiring major repairs. This observation, however, was based on bivariate associations between housing conditions and food insecurity and did not account for other factors such as socioeconomic conditions. These studies nonetheless suggest that food insecurity is not only explained in terms of low socioeconomic status and poverty.40,42We examined whether household crowding was associated with food insecurity among Inuit families with school-aged children, independently of socioeconomic disadvantage.     

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation

Background

Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.

Methods

Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.

Results

The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.

Conclusions

This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

Citation

Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264; http://dx.doi.org/10.1289/ehp.1408337     

Relation of Prenatal Methylmercury Exposure from Environmental Sources to Childhood IQ

Background

Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter.

Objectives

We aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec.

Methods

IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures.

Results

Prenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ.

Conclusions

To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.

Citation

Jacobson JL, Muckle G, Ayotte P, Dewailly É, Jacobson SW. 2015. Relation of prenatal methylmercury exposure from environmental sources to childhood IQ. Environ Health Perspect 123:827–833; http://dx.doi.org/10.1289/ehp.1408554