Modeling the enigma of complex disease etiology.

BACKGROUND: Complex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors. METHODS: Here we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model. RESULTS: We provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. The model is robust and flexible to capture new information as the understanding of complex disease improves. CONCLUSIONS: The Human Disease Ontology's Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The new model facilitates the comparison of etiological factors between complex, common and rare diseases and is available at the Human Disease Ontology website.

Alcohol ban during the COVID-19 pandemic lockdown: Lessons for preventing foetal alcohol spectrum disorder in South Africa.

During the two national lockdowns implemented in South Africa to curb the spread of the coronavirus disease 2019 (COVID-19) pandemic, the sale and consumption of alcoholic beverages were prohibited. There is observational evidence from the literature suggesting a drastic reduction in the emergency and trauma unit admissions in many South African hospitals and clinics with alcohol-related restrictions. This article explores the potential benefits of the restrictions placed on the sale and consumption of alcohol during the COVID-19 pandemic on preventing foetal alcohol spectrum disorder (FASD) in South Africa. Following the potential benefits of the alcohol bans, we recommended that the current South African national liquor policy and the 2012 South African government-drafted Bill for Control of Marketing of Alcoholic Beverages should be fully implemented and enforced. Furthermore, the 'best buys' by the World Health Organization (WHO) should be adapted (based on local evidence) and executed. Implementing the abovementioned policies can reduce alcohol abuse by limiting and regulating the manufacturing, distribution, advertising, sponsorship, promotion, physical availability and hours of sale of alcoholic beverages in South Africa.Contribution: This article shows that alcohol bans during the coronavirus disease 2019 (COVID-19) lockdown reduced the short-term effects of alcohol. We believe that this could be a game-changer for the prevention of FASD in South Africa and positively impact the incidence and prevalence of FASD. This piece provides evidence that policymakers, health practitioners and academics can use to continue advocating for stricter alcohol control measures in South Africa.

Proceedings of the 2021 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group.

The 2021 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was titled "Role of Parental Experiences in Offspring Outcomes". The theme was reflected in the presentations of two keynote speakers: Edward Levin, Ph.D., who spoke about the role of paternal exposures in offspring development, and Catherine Monk, Ph.D., who spoke about the effects of maternal exposures and maternal mental health on offspring development. The conference included updates from three government agencies, short presentations by junior and senior investigators showcasing late-breaking FASD research, a report on international efforts to streamline FASD classifications for research, a presentation of observations from adults with FASD, a short film of people with FASDs describing their experiences, and a poster session. The conference was capped by awarding the 2021 Henry Rosett award for career-long contributions to the field to Cynthia J.M. Kane, Ph.D.

Alcohol's Impact on the Fetus.

BACKGROUND: Alcohol is a teratogen and prenatal exposure may adversely impact the developing fetus, increasing risk for negative outcomes, including Fetal Alcohol Spectrum Disorder (FASD). Global trends of increasing alcohol use among women of childbearing age due to economic development, changing gender roles, increased availability of alcohol, peer pressure and social acceptability of women's alcohol use may put an increasing number of pregnancies at risk for prenatal alcohol exposure (PAE). This risk has been exacerbated by the ongoing COVID-19 pandemic in some countries. METHOD: This literature review presents an overview on the epidemiology of alcohol use among childbearing age and pregnant women and FASD by World Health Organization regions; impact of PAE on fetal health, including FASD; associated comorbidities; and social outcomes. RESULTS/CONCLUSION: The impact of alcohol on fetal health and social outcomes later in life is enormous, placing a huge economic burden on countries. Prevention of prenatal alcohol exposure and early identification of affected individuals should be a global public health priority.

Diagnosis of Fetal Alcohol Spectrum Disorders (FASDs): Guidelines of Interdisciplinary Group of Polish Professionals.

(1) Background: Considerable prevalence in Poland and serious health consequences of prenatal alcohol exposure indicated the need to develop national guidelines for the diagnosis of fetal alcohol spectrum disorders (FASDs). It was assumed that the guidelines must be in line with international standards but adjusted to the Polish context. (2) Methods: Work on recommendations was carried out by an interdisciplinary team of Polish specialists. Its first stage was to assess the usefulness in our country of the U.S. and Canadian guidelines. In the second stage, after several rounds of discussions, a consensus was achieved. (3) Results: The Polish guidelines for diagnosing FASD cover the following issues: 1. distinguished diagnostic categories; 2. diagnostic procedure; 3. assessment of prenatal exposure to alcohol; 4. assessment of sentinel facial dysmorphias; 5. assessment of body weight, height, and head circumference; 6. neurodevelopmental assessment. An important element of the recommendation is appendices containing practical tools that are useful in the diagnostic procedure. (4) Conclusions: National guidelines may improve the quality and standardization of FASD diagnosis in Poland, but their practical utility has to be monitored.

Neuroinflammation and Brain Development: Possible Risk Factors in COVID-19-Infected Children.

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.