Multiple Environmental Influences Research Articles

Shigella sonnei: epidemiology, evolution, pathogenesis, resistance and host interactions.

Shigella sonnei is a major cause of diarrhoea globally and is increasing in prevalence relative to other Shigella because of multiple demographic and environmental influences. This single-serotype species has traditionally received less attention in comparison to Shigella flexneri and Shigella dysenteriae, which were more common in low-income countries and more tractable in the laboratory. In recent years, we have learned that Shigella are highly complex and highly susceptible to environmental change, as exemplified by epidemiological trends and increasing relevance of S. sonnei. Ultimately, methods, tools and data generated from decades of detailed research into S. flexneri have been used to gain new insights into the epidemiology, microbiology and pathogenesis of S. sonnei. In parallel, widespread adoption of genomic surveillance has yielded insights into antimicrobial resistance, evolution and organism transmission. In this Review, we provide an overview of current knowledge of S. sonnei, highlighting recent insights into this globally disseminated antimicrobial-resistant pathogen and assessing how novel data may impact future vaccine development and implementation.

Dopamine Dysregulation in Reward and Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition and by repetitive stereotyped behaviors. These manifestations are variable between individuals, and ASD pathogenesis is complex, with over a thousand implicated genes, many epigenetic factors, and multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system is held to play a key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving a wide array of mesolimbic loci, neurotransmitters and receptor subtypes, and neuronal variants. How altered DA signaling may constitute a downstream convergence of the manifold causal origins of ASD is not well understood. A clear working framework of ASD pathogenesis may help delineate common stages and potential diagnostic and interventional opportunities. Hence, we summarize the known natural history of ASD in the context of emerging data and perspectives to update ASD reward signaling. Then, against this backdrop, we proffer a provisional framework that organizes ASD pathogenesis into successive levels, including (1) genetic and epigenetic changes, (2) disrupted mesolimbic reward signaling pathways, (3) dysregulated neurotransmitter/DA signaling, and finally, (4) altered neurocognitive and social behavior and possible antagonist/agonist based ASD interventions. This subdivision of ASD into a logical progression of potentially addressable parts may help facilitate the rational formulation of diagnostics and targeted treatments.

Neighborhood disadvantage and parenting predict longitudinal clustering of uncinate fasciculus microstructural integrity and clinical symptomatology in adolescents

Parenting behaviors and neighborhood environment influence the development of adolescents’ brains and behaviors. Simultaneous trajectories of brain and behavior, however, are understudied, especially in these environmental contexts. In this four-wave study spanning 9–18 years of age (N=224 at baseline, N=138 at final assessment) we used longitudinal k-means clustering to identify clusters of participants with distinct trajectories of uncinate fasciculus (UF) fractional anisotropy (FA) and anxiety symptoms; we examined behavioral outcomes and identified environmental factors that predicted cluster membership. We identified three clusters of participants: 1) high UF FA and low symptoms (“low-risk”); 2) low UF FA and high symptoms (“high-risk”); and 3) low UF FA and low symptoms (“resilient”). Adolescents in disadvantaged neighborhoods were more likely to be in the resilient than high-risk cluster if they also experienced maternal warmth. Thus, neighborhood disadvantage may confer neural risk for psychopathology that can be buffered by maternal warmth, highlighting the importance of considering multiple environmental influences in understanding emotional and neural development in youth.

Unraveling Complexities in Genetically Elusive Long QT Syndrome.

Genetic testing has become standard of care for patients with long QT syndrome (LQTS), providing diagnostic, prognostic, and therapeutic information for both probands and their family members. However, up to a quarter of patients with LQTS do not have identifiable Mendelian pathogenic variants in the currently known LQTS-associated genes. This absence of genetic confirmation, intriguingly, does not lessen the severity of LQTS, with the prognosis in these gene-elusive patients with unequivocal LQTS mirroring genotype-positive patients in the limited data available. Such a conundrum instigates an exploration into the causes of corrected QT interval (QTc) prolongation in these cases, unveiling a broad spectrum of potential scenarios and mechanisms. These include multiple environmental influences on QTc prolongation, exercise-induced repolarization abnormalities, and the profound implications of the constantly evolving nature of genetic testing and variant interpretation. In addition, the rapid advances in genetics have the potential to uncover new causal genes, and polygenic risk factors may aid in the diagnosis of high-risk patients. Navigating this multifaceted landscape requires a systematic approach and expert knowledge, integrating the dynamic nature of genetics and patient-specific influences for accurate diagnosis, management, and counseling of patients. The role of a subspecialized expert cardiogenetic clinic is paramount in evaluation to navigate this complexity. Amid these intricate aspects, this review outlines potential causes of gene-elusive LQTS. It also provides an outline for the evaluation of patients with negative and inconclusive genetic test results and underscores the need for ongoing adaptation and reassessment in our understanding of LQTS, as the complexities of gene-elusive LQTS are increasingly deciphered.

Species pool, local assembly processes: Disentangling the mechanisms determining bacterial α- and β-diversity during forest secondary succession.

Across ecology, and particularly within microbial ecology, there is limited understanding how the generation and maintenance of diversity. Although recent work has shown that both local assembly processes and species pools are important in structuring microbial communities, the relative contributions of these mechanisms remain an important question. Moreover, the roles of local assembly processes and species pools are drastically different when explicitly considering the potential for saturation or unsaturation, yet this issue is rarely addressed. Thus, we established a conceptual model that incorporated saturation theory into the microbiological domain to advance the understanding of mechanisms controlling soil bacterial diversity during forest secondary succession. Conceptual model hypotheses were tested by coupling soil bacterial diversity, local assembly processes and species pools using six different forest successional chronosequences distributed across multiple climate zones. Consistent with the unsaturated case proposed in our conceptual framework, we found that species pool consistently affected α-diversity, even while local assembly processes on local richness operate. In contrast, the effects of species pool on β-diversity disappeared once local assembly processes were taken into account, and changes in environmental conditions during secondary succession led to shifts in β-diversity through mediation of the strength of heterogeneous selection. Overall, this study represents one of the first to demonstrate that most local bacterial communities might be unsaturated, where the effect of species pool on α-diversity is robust to the consideration of multiple environmental influences, but β-diversity is constrained by environmental selection.

Environmental and Lifestyle Cancer Risk Factors: Shaping Extracellular Vesicle OncomiRs and Paving the Path to Cancer Development.

Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2 (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future.

Abstract 723: Positional Transcriptomics Defines Regionally Restricted Sex-specific Differences Of The Vessel Wall

Cardiovascular diseases (CVDs) remain the leading causes of morbidity and mortality for both men and women, globally. Abdominal aortic aneurysm (AAA) represents a class of CVD with significant sex-stratification as disease burden is higher in males, but outcome of disease is poorer in females. Establishment of AAA is a complex process, defined by the interaction of multiple environmental influences and host regional vascular heterogeneity. While is it is known that many factors including developmental origin, local cellular diversity and regional bio-mechanical forces contribute to vascular bed specialization, the exact contribution of biological sex in vascular heterogeneity remains unknown. To elucidate the molecular contribution of sex to vascular heterogeneity of large arterial beds we performed single cell sequencing from cells isolated from 4 distinct anatomic locations of both male and female young adult mice: the carotid arteries, aortic arch, thoracic and abdominal aorta. Using this approach, we identified anatomic sex-invariant gene signatures as well as regional sex-specific gene signatures in vascular smooth muscle cells (vSMC) and used immunohistochemistry to validate these findings. Surprisingly, prominent regional-sex dependent differences were observed in vSMCs of the thoracic and abdominal aorta, consistent with sex-specific burden of aneurysm in these regions. From these sex-specific regionally restricted vSMC signatures, we identified several enriched signature genes that are likely contributors in the regulation of AAA development in mice and humans.

The importance of embracing complexity in rehabilitation.

The importance of embracing complexity in rehabilitation.

Preventing Parkinson's Disease: An Environmental Agenda.

Fueled by aging populations and continued environmental contamination, the global burden of Parkinson’s disease (PD) is increasing. The disease, or more appropriately diseases, have multiple environmental and genetic influences but no approved disease modifying therapy. Additionally, efforts to prevent this debilitating disease have been limited. As numerous environmental contaminants (e.g., pesticides, metals, industrial chemicals) are implicated in PD, disease prevention is possible. To reduce the burden of PD, we have compiled preclinical and clinical research priorities that highlight both disease prediction and primary prevention. Though not exhaustive, the “PD prevention agenda” builds upon many years of research by our colleagues and proposes next steps through the lens of modifiable risk factors. The agenda identifies ten specific areas of further inquiry and considers the funding and policy changes that will be necessary to help prevent the world’s fastest growing brain disease.

Multiple Environmental Influences on the Lightning of Cold-Based Continental Convection. Part II: Sensitivity Tests for Its Charge Structure and Land–Ocean Contrast

Abstract In Part I, an electrification scheme was described and a simulation of an observed cold-based storm from the U.S. Great Plains was validated with electrical observations. Most charge in the storm was separated by rebounding collisions of secondary ice originating from prior graupel–snow collisions. In this Part II, sensitivity tests are performed with the control simulation (Part I) and influences from environmental factors (aerosols, temperature, moisture, and shear) on lightning are elucidated. Environmental factors [e.g., convective available potential energy (CAPE)] controlling updraft speed are salient. When ascent is reduced by 30% and 70%, flashes become 70% fewer and disappear, respectively; faster ascent promotes positive cloud-to-ground (+CGs) flashes. Since cloud base is too cold (1°C) for coalescence, cloud condensation nucleus aerosol concentrations do not influence the lightning appreciably. The electrical response to varying concentrations of active ice nuclei is limited by most ice particles being secondary and less sensitive—a natural “buffer.” Imposing a maritime sounding suggests that the land–sea contrast in lightning for such storms is due to the vertical structure of environmental temperature and humidity. Weak CAPE, and both entrainment and condensate weight from a low cloud base, suppress ascent and charging. Maritime thermodynamic conditions reduce simulated flash rates by two orders of magnitude. Reducing aerosol loadings from continental to maritime only slightly reinforces this suppression. Last, a conceptual model is provided for how any simulated storm is either normal because graupel/hail is mostly positively charged or else is inverted/anomalous because graupel/hail is mostly negatively charged, with environmental factors controlling the charging. Impacts from microphysical processes, including three processes of secondary ice production, on lightning are analyzed.

The good, the bad, and the environment: developing an area-based measure of access to health-promoting and health-constraining environments in New Zealand

BackgroundAccounting for the co-occurrence of multiple environmental influences is a more accurate reflection of population exposure than considering isolated influences, aiding in understanding the complex interactions between environments, behaviour and health. This study examines how environmental ‘goods’ such as green spaces and environmental ‘bads’ such as alcohol outlets co-occur to develop a nationwide area-level healthy location index (HLI) for New Zealand.MethodsNationwide data were collected, processed, and geocoded on a comprehensive range of environmental exposures. Health-constraining ‘bads’ were represented by: (i) fast-food outlets, (ii) takeaway outlets, (iii) dairy outlets and convenience stores, (iv) alcohol outlets, (v) and gaming venues. Health-promoting ‘goods’ were represented by: (i) green spaces, (ii) blue spaces, (iii) physical activity facilities, (iv) fruit and vegetable outlets, and (v) supermarkets. The HLI was developed based on ranked access to environmental domains. The HLI was then used to investigate socio-spatial patterning by area-level deprivation and rural/urban classification.ResultsResults showed environmental ‘goods’ and ‘bads’ co-occurred together and were patterned by area-level deprivation. The novel HLI shows that the most deprived areas of New Zealand often have the most environmental ‘bads’ and less access to environmental ‘goods’.ConclusionsThe index, that is now publicly available, is able to capture both inter-regional and local variations in accessibility to health-promoting and health-constraining environments and their combination. Results in this study further reinforce the need to embrace the multidimensional nature of neighbourhood and place not only when designing health-promoting places, but also when studying the effect of existing built environments on population health.

Multiple Environmental Influences on the Lightning of Cold-Based Continental Cumulonimbus Clouds. Part I: Description and Validation of Model

AbstractIn this two-part paper, influences from environmental factors on lightning in a convective storm are assessed with a model. In Part I, an electrical component is described and applied in the Aerosol–Cloud model (AC). AC treats many types of secondary (e.g., breakup in ice–ice collisions, raindrop-freezing fragmentation, rime splintering) and primary (heterogeneous, homogeneous freezing) ice initiation. AC represents lightning flashes with a statistical treatment of branching from a fractal law constrained by video imagery.The storm simulated is from the Severe Thunderstorm Electrification and Precipitation Study (STEPS; 19/20 June 2000). The simulation was validated microphysically [e.g., ice/droplet concentrations and mean sizes, liquid water content (LWC), reflectivity, surface precipitation] and dynamically (e.g., ascent) in our 2017 paper. Predicted ice concentrations (~10 L−1) agreed—to within a factor of about 2—with aircraft data at flight levels (−10° to −15°C). Here, electrical statistics of the same simulation are compared with observations. Flash rates (to within a factor of 2), triggering altitudes and polarity of flashes, and electric fields, all agree with the coincident STEPS observations.The “normal” tripole of charge structure observed during an electrical balloon sounding is reproduced by AC. It is related to reversal of polarity of noninductive charging in ice–ice collisions seen in laboratory experiments when temperature or LWC are varied. Positively charged graupel and negatively charged snow at most midlevels, charged away from the fastest updrafts, is predicted to cause the normal tripole. Total charge separated in the simulated storm is dominated by collisions involving secondary ice from fragmentation in graupel–snow collisions.

How Older Citizens in Germany Perceive and Handle Their Food Environment-A Qualitative Exploratory Study.

Apart from individual factors like knowledge or personal motivation, the environment also influences a person’s eating behaviour. Food environments can be described as the collective physical, economic, policy and sociocultural surroundings, opportunities and conditions that influence people’s food choices and nutritional status. In order to explore how older citizens in rural Germany perceive and handle their food environment, we conducted semi-structured face-to-face interviews with 35 older adults (71 ± 7 years), asking about micro-, meso- and macro-level influences on eating habits. Participants reported social factors to be crucial in shaping their diets, such as preferences of family members or social expectations connected to roles (guest, host). On a physical level, structural aspects and resources in their nearby surroundings influenced shopping and eating behaviour (for example access to an own vegetable garden, local shopping facilities and restaurants). Macro-level influences such as the food industry were hardly mentioned. Participants noticed that the environment affects their diets but dealt with undesired influences using strategies of adaptation and behaviour change, rather than challenging the environmental influences. Public health projects should raise the awareness of the multiple environmental influences on eating behaviour and also help people to create healthier food environments.

Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson's Disease.

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.

The microbiome and rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a severe, chronic autoimmune disease that affects 1% of the world's population. Familial risk contributes 50% of the risk of seropositive RA, with strongest risks seen in first-degree relatives. Smoking increases the risk of developing anti-citrullinated peptide antibody (ACPA)+ RA, particularly in individuals with high-risk RA-susceptibility alleles. Other contributory environmental risks including particulate exposure, periodontal disease, bronchiectasis, diet, obesity and the oral contraceptive impact respiratory, oral, intestinal and genital tract mucosal sites. Furthermore, the first signs of autoimmunity may appear at mucosal sites e.g. sputum ACPA-IgA and IgG. While oral and faecal dysbiosis are well described, there is no consistent single bacterial species that appears to drive RA. Animal and human data suggest a model in which multiple environmental influences impact mucosal immune function through the host genetics through enhanced mucosal permeability and the traffic of pro-inflammatory PAMPs and the amplification of autoimmune responses. In some cases, autoimmunity may be driven by cross-reactivity, or mimicry, to pathogen-specific antigens, particularly where the host immune system fails to support their rapid control and elimination.

Standardizing Safety Assessment and Reporting for Neonatal Clinical Trials

Standardizing Safety Assessment and Reporting for Neonatal Clinical Trials

Building the evidence for an ecological model of cognitive health.

This is a commentary on Besser and colleagues' article "Associations between neighbourhood built environment and cognition vary by apolipoprotein E genotype: Multi-Ethnic Study on Atherosclerosis" published in Health & Place. Unlike previous studies, the authors found significant environment-cognition associations in apolipoprotein E (APOE) ε2 carriers and no significant associations in ε4 carriers. This commentary discusses the possible reasons for these findings and, in doing so, proposes an ecological model of cognitive health. The model highlights the importance of accounting for multiple environmental influences including the built and natural environment and air and noise pollution indicators. It also stresses the importance of studying the underlying biological mechanisms explaining differences in environment-cognition associations across APOE genotype categories.

Developmental Programming of PCOS Traits: Insights from the Sheep.

Polycystic ovary syndrome (PCOS) is a complex disorder that results from a combination of multiple factors, including genetic, epigenetic, and environmental influences. Evidence from clinical and preclinical studies indicates that elevated intrauterine androgen levels increase the susceptibility of the female offspring to develop the PCOS phenotype. Additionally, early postnatal endocrine and metabolic imbalances may act as a “second-hit”, which, through activational effects, might unmask or amplify the modifications programmed prenatally, thus culminating in the development of adult disease. Animal models provide unparalleled resources to investigate the effects of prenatal exposure to androgen excess and to elucidate the etiology and progression of disease conditions associated with this occurrence, such as PCOS. In sheep, prenatal treatment with testosterone disrupts the developmental trajectory of the fetus, culminating in adult neuroendocrine, ovarian, and metabolic perturbations that closely resemble those seen in women with PCOS. Our longitudinal studies clearly demonstrate that prenatal exposure to testosterone excess affects both the reproductive and the metabolic systems, leading to a self-perpetuating cycle with defects in one system having an impact on the other. These observations in the sheep suggest that intervention strategies targeting multiple organ systems may be required to prevent the progression of developmentally programmed disorders.

Cesarean Section and Development of Childhood Bronchial Asthma: Is There A Risk?

BACKGROUND:Asthma is a chronic inflammatory disease of the airways that results from complex interactions between multiple environmental and genetic influences. In recent years, studies have observed an increase in caesarean section rates, and have suggested a strong association with the rapid increase in the incidence of childhood asthma that cannot be explained by genetic factors alone. In this case-control study, we investigate the association between the developments of childhood asthma with the mode of delivery. We also explored the relationship between mode of delivery and control of asthma.METHODS:Two groups (509 pediatric patients in total) were assessed between January 1, 2017, and January 1, 2018. Part of these patients, 257 (50.4%) were asthmatic children visiting specialised clinics, and 252 (49.6%) controlled cases selected from a primary health care clinic from the same institution (control group).RESULTS:The Chi-square test revealed a significant association between cesarean sections and bronchial asthma (OR, 1.483 [95% CI, 1.013–21.71]; P =0.042). However, the adjusted OR from our binary logistic regression model revealed this association to be insignificant (adjusted OR, 1.417 [95% CI, 0.885–2.269]; P =0.804). The value of the chi-square of the model shows that the overall model is statistically significant at 1%. The Nagelkerke R square indicates that 34.9% of the variation in having asthma is explained by the risk factors included in the model.CONCLUSION:We do not believe that the rise in cesarean sections explains the increase in childhood bronchial asthma – at least not in our population. We also found no association between the mode of delivery and asthma control. We encourage further research into this topic, namely to recruit a larger number of patients, and to adjust for the significant risk factors found in our study.

Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012

Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes.