Contaminant Metals and Cardiovascular Health.

A growing body of research has begun to link exposure to environmental contaminants, such as heavy metals, with a variety of negative health outcomes. In this paper, we sought to review the current research describing the impact of certain common contaminant metals on cardiovascular (CV) health. We reviewed ten metals: lead, barium, nickel, chromium, cadmium, arsenic, mercury, selenium, zinc, and copper. After a literature review, we briefly summarized the routes of environmental exposure, pathophysiological mechanisms, CV health impacts, and exposure prevention and/or mitigation strategies for each metal. The resulting article discloses a broad spectrum of pathological significance, from relatively benign substances with little to no described effects on CV health, such as chromium and selenium, to substances with a wide-ranging and relatively severe spectrum of CV pathologies, such as arsenic, cadmium, and lead. It is our hope that this article will provide clinicians with a practical overview of the impact of these common environmental contaminants on CV health as well as highlight areas that require further investigation to better understand how these metals impact the incidence and progression of CV diseases.

Associations of Antihypertensive Medication Consumption and Drug-Drug Interaction with Statin and Metformin with Reduced Alzheimer's Disease and Related Dementias Risk among Hypertensive Patients with Mild Cognitive Impairment using High Volume Claims Data.

Background: While hypertension is a modifiable risk factor of Alzheimer's disease and related dementias (ADRD), limited studies have been conducted on the effectiveness of antihypertensive medications (AHMs) in altering the progression from mild cognitive impairment (MCI) to ADRD; similarly, few studies have assessed drug-drug interactions of AHMs with drugs targeted to modify other risk factors of ADRD such as type II diabetes and hypercholesterolemia. Method: 128,683 unique hypertensive patients with MCI on US-based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and the use of Statins and Metformin. To examine the association of AHM-Statin or AHM-Metformin interaction with ADRD progression, we also investigated models controlling for the aforementioned confounders, as well as drug-drug interactions. Result: The study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs during the study period. AHM users had a higher incidence of comorbidities (all P≤0.039) and consumption of Metformin and Statins (both P<0.001) compared to non-users. Users of each major AHM class showed significantly lower risk of developing ADRD compared to non-users of that specific drug class (adjusted hazard ratio (aHR): 0.96-0.98; all P≤0.048). Within patients on monotherapy (using only one AHM drug), no specific AHM class had significantly lower risk of ADRD diagnosis compared to other AHM drug classes (aHR: 0.97-1.11; all P≥0.053). Use of Diuretics or CCBs in combination with Metformin consumption (aHR: 0.89, 0.91, respectively) showed lower risk of MCI to ADRD progression than use without Metformin consumption (aHR: 0.97, 0.98, respectively), whereas use of any of the five major AHMs with Statin consumption (aHR: 0.91-0.94) all showed lower risk than without Statin consumption (aHR: 0.98-1.04). Conclusion: All five major AHM classes showed a protective effect against ADRD progression among hypertensive patients with MCI. Also, certain combinations of AHMs with Metformin or Statins showed a stronger protective effect compared to AHMs alone, and some drug-drug interactions of AHM-Metformin or AHM-Statin also showed protective effects against progression from MCI to ADRD.

One Health surveillance-A cross-sectoral detection, characterization, and notification of foodborne pathogens.

Introduction: Several Proficiency Test (PT) or External Quality Assessment (EQA) schemes are currently available for assessing the ability of laboratories to detect and characterize enteropathogenic bacteria, but they are usually targeting one sector, covering either public health, food safety or animal health. In addition to sector-specific PTs/EQAs for detection, cross-sectoral panels would be useful for assessment of the capacity to detect and characterize foodborne pathogens in a One Health (OH) perspective and further improving food safety and interpretation of cross-sectoral surveillance data. The aims of the study were to assess the cross-sectoral capability of European public health, animal health and food safety laboratories to detect, characterize and notify findings of the foodborne pathogens Campylobacter spp., Salmonella spp. and Yersinia enterocolitica, and to develop recommendations for future cross-sectoral PTs and EQAs within OH. The PT/EQA scheme developed within this study consisted of a test panel of five samples, designed to represent a theoretical outbreak scenario. Methods: A total of 15 laboratories from animal health, public health and food safety sectors were enrolled in eight countries: Denmark, France, Italy, the Netherlands, Poland, Spain, Sweden, and the United Kingdom. The laboratories analyzed the samples according to the methods used in the laboratory and reported the target organisms at species level, and if applicable, serovar for Salmonella and bioserotype for Yersinia. Results: All 15 laboratories analyzed the samples for Salmonella, 13 for Campylobacter and 11 for Yersinia. Analytical errors were predominately false negative results. One sample (S. Stockholm and Y. enterocolitica O:3/BT4) with lower concentrations of target organisms was especially challenging, resulting in six out of seven false negative results. These findings were associated with laboratories using smaller sample sizes and not using enrichment methods. Detection of Salmonella was most commonly mandatory to notify within the three sectors in the eight countries participating in the pilot whereas findings of Campylobacter and Y. enterocolitica were notifiable from human samples, but less commonly from animal and food samples. Discussion: The results of the pilot PT/EQA conducted in this study confirmed the possibility to apply a cross-sectoral approach for assessment of the joint OH capacity to detect and characterize foodborne pathogens.

Cerebrospinal fluid and serum protein markers in autism: A co-twin study.

No robust biomarkers have yet been identified for autism spectrum disorder (ASD) or autistic traits. Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co-twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (n = 86) and serum (n = 127) in twins (mean age 14.2 years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent-report version of the Social Responsiveness Scale-2. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively-and one negatively-associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B-cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations did not remain significant when only considering monozygotic twins. For the remainder, the within-pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication.

Functional gender differences in autism: An international, multidisciplinary expert survey using the International Classification of Functioning, Disability, and Health model.

LAY ABSTRACT: In this study, we explored if professionals working with autistic people in different regions of the world perceive differences between females and males diagnosed with the condition. A total of 131 professionals responded to a survey that included an open question about gender differences in autism. Of these, 32 responded that they do not perceive gender differences in autism. The information provided by the other 99 experts was analyzed to identify common patterns. Three main differences were found, (1) Matching the clinical conceptualization of autism where professionals described differences in core symptoms of autism, and that autistic females were less similar to the conceptualization of autism. In (2) Co-existing problems, professionals described that autistic males display more apparent problems including hyperactivity, while autistic females were perceived as having more internalizing issues such as anxiety and eating disorders. In the last category, (3) Navigating the social environment, experts perceived autistic females as more socially motivated, and more inclined to camouflage social difficulties, making their challenges less evident. Professionals also perceived differences in the social environment, for example, that autistic girls receive more support from their peers while autistic boys are more often bullied. Our results suggest that professionals working in different parts of the world acknowledge gender differences in autism, but also that there might be some regional differences. Finally, we found that gender differences reported by the international professionals could largely be assessed with a shortened version of the International Classification of Functioning by the World Health Organization, specifically developed for autism.

Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders.

While previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8-36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00-1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03-1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

Clinical versus automated assessments of morphological variants in twins with and without neurodevelopmental disorders.

Physical examinations are recommended as part of a comprehensive evaluation for individuals with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder. These examinations should include assessment for morphological variants. Previous studies have shown an increase in morphological variants in individuals with NDDs, particularly ASD, and that these variants may be present in greater amounts in individuals with genetic alterations. Unfortunately, assessment for morphological variants can be subjective and time-consuming, and require a high degree of clinical expertise. Therefore, objective, automated methods of morphological assessment are desirable. This study compared the use of Face2Gene, an automated tool to explore facial morphological variants, to clinical consensus assessment, using a cohort of N = 290 twins enriched for NDDs (n = 135 with NDD diagnoses). Agreement between automated and clinical assessments were satisfactory to complete (78.3-100%). In our twin sample, individuals with NDDs did not have greater numbers of facial morphological variants when compared to those with typical development, nor when controlling for shared genetic and environmental factors within twin pairs. Common facial morphological variants in those with and without NDDs were similar and included thick upper lip vermilion, abnormality of the nasal tip, long face, and upslanted palpebral fissure. We conclude that although facial morphological variants can be assessed reliably in NDDs with automated tools like Face2Gene, clinical utility is limited when just exploring the facial region. Therefore, currently, automated assessments may best complement, rather than replace, in-person clinical assessments.

Familial confounding on the ability to read minds: A co-twin control study.

Alterations in social cognition are hypothesized to underlie social communication challenges in autism spectrum disorder. However, the etiologic underpinnings driving this association, as well as the impact of other psychiatric conditions on the association, remain unclear. Using a co-twin control design, we examined n = 308 twins (mean age = 16.63; 46% females) with autism spectrum disorder, attention-deficit/hyperactivity disorder, affective disorders, or typical development using the Reading the Mind in the Eyes Test to operationalize social cognition ability. Clinical diagnosis of autism spectrum disorder, as well as the extent of quantitative autistic traits, as measured by parental reports using the Social Responsiveness Scale-2, predicted fewer expected responses on the Reading the Mind in the Eyes Test across the pairs. The association remained when adjusting for other diagnoses and IQ. In addition, male sex, lower age, and lower IQ predicted poorer performance on the Reading the Mind in the Eyes Test. The associations between autism and social cognition ability were lost within pairs in both the full sample and the monozygotic subsample. We conclude that the association between autism and social cognition across the sample highlights the importance of social cognition alterations in autism spectrum disorder when compared with other conditions. The attenuation of the association in the within-pair models indicate familial confounding, such as genes and shared environment, influencing both autism and social cognition.

EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort.

EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.

Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease.

INTRODUCTION: Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease. METHODS: Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic. RESULTS: Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44-7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia. CONCLUSIONS: Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.