Causes of Down syndrome regression disorder: a scoping review

Racial/Ethnic and Nativity Inequalities in Gestational Diabetes Mellitus: The Role of Psychosocial Stressors.

Lifestyle related factors such as obesity, drinking habits, sodium and potassium intake and physical inactivity are well established determinants of high blood pressure. The role of psycho-social stressors, and in particular environmental work or home stress is far less clear. Some but not all studies using the Karasek ‘job-strain’ model have found a relationship with ambulatory blood pressure levels. Other studies using more ‘subjective’ measures of occupational stress have found no relationship or even inverse associations with blood pressure. The possibility that relationships between external stressors, personality factors and blood pressure levels might be mediated or confounded by coping mechanisms influencing lifestyle factors known to directly affect blood pressure has not been adequately studied. This paper briefly explores the paradigm relating environmental psychosocial stress, individual coping mechanisms, lifestyle behaviours and blood pressure levels.The issues are critical for research methodology in this area and for the development of better behavioural strategies for the prevention and nonpharmacologicalmanagement of hypertension.

Introduction: Snakebite is a neglected tropical disease and a common medical emergency in the tropics. Envenoming in humans activates both innate and adaptive immune responses, which play a pivotal role in host defence against venom toxins. On the other hand, a dysregulated immune response triggers devastating pathophysiological effects related to venom-induced, immune-mediated host damage, causing tissue injury or organ damage, oxidative stress, angiogenesis, and fibrosis in diverse target tissues. While there is evidence of an association between immune dysregulation and the clinical features of severe envenoming, the role of immune mediators in the pathophysiology of snakebite envenoming, contributing to the development of severe clinical features, remains to be elucidated. Our scoping review aims to summarise the role of immune mediators in pathophysiological events following snakebite envenoming and antivenom treatment.Method and analysis: The scoping review will follow Arksey and O'Malley's scoping review framework and the guidance recommended by the Joanna Briggs Institute (JBI). MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases will be searched using predefined keywords to gather the peer-reviewed, English-language articles reporting original data from 2000 to the present. All reviews will involve two or more reviewers. Data will be presented in a descriptive manner, and tables and figures will be used when necessary.Ethics and dissemination: A scoping review does not require ethics approval since it will rely on secondary data. Once the review is completed, we anticipate submitting it for publication in a peer-reviewed journal.

Retrospective and prospective biobehavioral cancer studies have revealed that psychosocial stressors may play a pivotal role in the initiation and progression of malignant neoplasia. In recent research, a pattern has emerged, which in analogy to the coronary prone pattern (type A) has been labelled type C, encompassing suppression of emotional responses, such as anger and hostility, rationality and antiemotionality, as well as high social conformity and a lack of self-assertiveness. There is growing evidence in both infrahuman and human research that specific coping styles (repressive coping) with stress may be associated with specific biologic responses, including neuroendocrine, immunologic and other bodily functions. The application of this model appears to be of importance for further research, as well as for the detection of high risk individuals, but also in regard to therapy, rehabilitation, early detection and possibly also prevention of malignant disease. This concept suggests also new directions and modifications of stress research, as stressors are to be viewed not necessarily as pathological, but in some instances as quite possibly salutary, depending on the nature of the stressor, the psychophysiologic state of the individual and his or her ability to cope with adverse life situations. Quite naturally, the development of this concept is still in its initial stages, there remain a number of open questions, and it needs hardly to be pointed out in this connection that further and painstaking clinical and laboratory work is warranted in order to clarify the role of stressors, life and coping styles and its biological concomitants in neoplastic disease.

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player in dyslipidemia and is linked to cardiovascular disease risk. To our knowledge, the potential link between psychosocial stressors, PCSK9 levels, and related dyslipidemia has not been evaluated. Hypothesis: IFNγ mediates the association between amygdalar activity (AmygA) and PCSK9. Methods: Participants from the D.C. Cardiovascular Health and Needs Assessment (DC-CHNA), a community-engaged cohort study, were recruited to the NIH Clinical Center and underwent phenotyping, including 18 FDG PET/CT to assess AmygA as a marker of chronic stress-related neural activity. Cytokines, PCSK9, and lipoprotein (a) (Lp(a)) were measured using ELISA-based techniques. Regression modeling identified associations between AmygA and PCSK9 and between PCSK9 and Lp(a) while adjusting for atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and body mass index (BMI). Mediation analysis was used to evaluate IFNγ, TNFα, and IL-6 as potential mediators. Results: The DC-CHNA consisted of 60 African American participants (mean age 61±11 years, 93% female) at risk for ASCVD. AmygA associated with PCSK9 and IFNγ after adjusting for ASCVD and BMI; additionally, IFNγ associated with PCSK9 ( Figure ). Mediation analysis indicated that IFNγ mediated 45.8% of the AmygA and PCSK9 relationship. TNFα and IL-6 did not mediate the relationship. Lastly, PCSK9 associated with Lp(a) independent of ASCVD risk factors (β=0.34, p=0.013). Conclusions: The role of psychosocial stressors in PCSK9 related-dyslipidemia is not well known. Thus, we show that AmygA, a measure of chronic stress, associated with PCSK9 in an IFNγ-mediated fashion. PCSK9 then associated with Lp(a) which is notable as Lp(a) is thought to be largely genetically determined and highly atherogenic. Future research should further this hypothesis-generating study by prospectively investigating the impact of psychosocial stressors on PCSK9 and dyslipidemia in larger, diverse populations.

Down Syndrome (DS) is caused by trisomy of HSA21 in humans and is the most common autosomal aneuploidy, occurring in about 1 in 700 live births. DS is a major genetic cause of intellectual disability and is characterised by a reduction in the size and altered morphology of the brain. DS is also associated with immunological dysfunction, with sufferers being more susceptible to infection and having a higher incidence of both autoimmune disorders and haematological cancers. Many of the immune deficits observed in DS are T cell dependent, with T cell development and function adversely affected. One of the genes located on HSA21 that is believed to contribute to some of the DS phenotypes is Regulator of Calcineurin 1 or RCAN1. In order investigate the effects of over expression of RCAN1 on the brain and immune system we used mice over expressing RCAN1. In this study we found that over expression of RCAN1 in the brain resulted in multiple defects in the formation, structure and function of the hippocampus and these structural abnormalities were accompanied by cognitive impairments. We also reveal that over expression of RCAN1 in mice replicates a subset of the immune deficiencies observed in DS. Specifically, RCAN1-TG mice exhibited impaired T cell development and maturation within the thymus as well as T cell functional deficits characterised by a reduced proliferative capacity and aberrant cytokine production. In a separate study we found that increased levels of RCAN1 provided protection against ischaemic damage (stroke) in the brain by decreasing neuronal cell death and reducing inflammation. Based on the results presented in this study we have demonstrated that RCAN1 plays an important role in the development and function of the neurological and the immune systems and when over expressed, may be a key contributor to the abnormal phenotypes intrinsic to DS, yet protective in stroke.

People with Down syndrome (DS), the genetic condition caused by trisomy of chromosome 21 (chr21), have an altered disease spectrum. For example, adults with DS are largely protected from solid tumors while predisposed to various autoimmune disorders, early-onset Alzheimer’s disease, and severe respiratory infection. While the immune system is known to play a key role in these comorbidities among the disomic population, there is a dearth of immune studies in adults with DS. Here, we applied the single-cell, systems-level approach of mass-cytometry, or Cytometry by Time-Of-Flight (CyTOF), to broadly define phenotypic and functional alterations in immune homeostasis in adults with DS that are relevant to the potentiation of comorbidities associated with T21. We developed an innovative strategy to analyze CyTOF data, by incorporating techniques commonly used in genomics and even topography to eliminate batch bias and efficiently resolve ~100 immune cell types. This approach revealed that adults with DS have global immune dysregulation reminiscent of various inflammatory and autoimmune states enriched among older individuals of the disomic population. Upon stimulation directly ex vivo with Type I Interferon (IFN) and simultaneous detection of diverse phosphorylation events across the lymphoid and myeloid lineages, all immune subsets from individuals with T21 were hyper-responsive, but the degree of response and signaling pathways used varied among specific cell types. Notably, 4 of the 6 IFN receptor subunits for Types I, II, and III IFNs are encoded on chr21. Altogether, these results establish a critical foundation to pursue immune dysregulation and IFN hyperactivity as a driver of the altered disease spectrum in adults with DS.

Functional neurological disorder (FND) is a common and highly disabling disorder, but its aetiology remains enigmatic. Conceptually, there has been reduced emphasis on the role of psychosocial stressors in recent...

Biological and perceived stress in motor functional neurological disorders

The aim: to study the possible role of psychosocial stressors in the emergence of anomalies of childbirth, as well as to examine their nature using the example of pregnant women who have been forcefully displaced from Donetsk and Luhansk regions of Ukraine. Materials and methods: 115 internally displaced pregnant women from Donetsk and Luhansk regions, were surveyed. All women underwent a comprehensive neuropsychological examination of their psycho-emotional status via interviews, questioning, and psychological testing (Spielberg-Haning's Situational and Personal Anxiety Scale). The following analysis of the childbirth process' nature was conducted. Results: The prevalence of high level of situational and personal anxiety by the Spielberg-Haning's test were determined in the internally displaced women. This indicates a high level of social anxiety (stress) in these pregnant women. Labours in women in this group can be characterized by 3 main features: rapid (precipitated) labour with high levels of obstetric traumatism (tear of perineum) and labour medicalization (EDA). The characteristics described above are due to such labour activity anomalies as hypertensive uterine dysfunction - the cases when the speed and strength of uterine contractions significantly exceed the normative parameters. The reasons for the high level of pain in labour in displaced women could be objecttive and subjective factors: excessive nociceptor irritation due to cervical-uterine dysfunction and impaired individual perception of pain. Conclusions: Chronic psychosocial stress has an impact on labour activity in displaced women. A mandatory standard for managing such pregnancy is psychological counselling and correction of the identified disorders.

Adverse birth outcomes, such as preterm birth, low birthweight, and small for gestational age, are critical indicators of neonatal health. While the impact of biomedical risk factors is well established, the role of psychosocial stressors, including intimate partner violence, remains less understood. This study investigates the association between intimate partner violence among pregnant women and adverse birth outcomes in a Danish context. Based on routinely collected Patient-Reported Outcomes, we conducted a cohort study, including 28 697 pregnant individuals. Enrolled in the period from November 2019 to September 2022, the women were followed until childbirth, leading to 22 799 mothers-offspring pairs with valid data. Data on IPV exposure were collected through the Abuse Assessment Screen, detecting physical, psychological, and sexual violence and fear of partner. Birth outcomes were obtained from the Danish registries, including the Danish medical birth registry. Generalized linear models (GLMs) were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs), adjusting for confounders, such as maternal age, socioeconomic position, smoking status, and psychiatric disorders. Of the 22 799 mothers, 5.3% screened positive for intimate partner violence, and 1.9% reported intimate partner violence within the last year. Intimate partner violence was positively associated with preterm birth and low birthweight, with an increased risk of preterm birth (adjusted RR: 1.24, 95% CI 1.06, 1.45) and increased risk for low birthweight (adjusted RR: 1.35, 95% CI 1.04, 1.75) but showed no significant association with small for gestational age (adjusted RR: 0.93, 95% CI 0.78, 1.11). Our analysis demonstrates a significantly heightened risk of preterm birth and low birthweight among pregnant women who screened positive for intimate partner violence. These results underscore the need for targeted intimate partner violence screening and intervention strategies during prenatal care to reduce the burden of adverse birth outcomes.

This paper focuses on one category of mental illness, the personality disorders, and discusses them from an interactional personality perspective. After reviewing the classification of mental disorders from a historical perspective, we briefly discuss the DSM–III with special emphasis on one of the multiaxial axes, the personality disorders. The role of psychosocial Stressors (Axis IV) is also described. We then discuss Leary's and Benjamin's interpersonal classification models and indicate why an interactional (Person by Situation) classification model (Endler) would be a more appropriate nosology. Finally, we discuss the relationship between diagnosis and treatment, and indicate that a complete classification scheme would have to link diagnoses with appropriate and specific treatments.

Psychiatric Evaluation of the Dermatology Patient

Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2 receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.

Health equity and e-cigarette use among young adults in rural areas: A social determinants of health framework.