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1.
The Impact of Genetic Variability of TGF-Beta Signaling Biomarkers in Major Craniofacial Syndromes.
Yapijakis, C, Davaria, S, Gintoni, I, Chrousos, GP
Advances in experimental medicine and biology. 2023;:187-191
Abstract
Craniofacial development is a complex process involving several signaling pathways, including the one regulated by the TGF-beta (TGF-β) superfamily of growth factors. Isoforms of TGF-β play a vital part in embryonic development, notably in craniofacial patterning. Consequently, pathogenic variants in their coding genes may result in a variety of orofacial and craniofacial malformations. Here, we review the impact of genetic variability of TGF-β signaling biomarkers in major disorders, including palatal and lip clefts, dental anomalies, and craniofacial syndromes, such as the Loeys-Dietz syndrome (LDS) and Camurati-Engelmann disease. Cleft lip and cleft palate are associated with missense mutations in the TGFB1 and TGFB3 genes, while mutations in the LTBP3 gene encoding TGF-β binding protein 3 may cause selective tooth agenesis. Oligodontia may also be caused by TGFB1-inactivating mutations and/or by variations in the GREM2 gene, which disrupt the activity of gremlin 2, a TGF-β/bone morphogenetic protein (BMP4) signaling antagonist. CED may be caused by mutations in the TGFB1 gene, while the TGF-β-related genetic background of LDS consists mostly of TGFBR1 and TGFBR2 mutations, which may also impact the above syndromes' vascular manifestations. The potential utility of the TGF-β signaling pathway factors as biomarkers that correlate genetics with clinical outcome of craniofacial malformations is discussed.
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2.
Amyotrophic lateral sclerosis (ALS) and the endocrine system: Are there any further ties to be explored?
Mentis, AA, Bougea, AM, Chrousos, GP
Aging brain. 2021;:100024
Abstract
Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular atrophy, primary lateral sclerosis, and pseudobulbar palsy. Even though endocrine dysfunction independently impacts the ALS-related survival rate, the complex connection between ALS and the endocrine system has not been studied in depth. Here we review earlier and recent findings on how ALS interacts with hormones a) of the hypothalamus and pituitary gland, b) the thyroid gland, c) the pancreas, d) the adipose tissue, e) the parathyroid glands, f) the bones, g) the adrenal glands, and h) the gonads (ovaries and testes). Of note, endocrine issues should always be explored in patients with ALS, especially those with low skeletal muscle and bone mass, vitamin D deficiency, and decreased insulin sensitivity (diabetes mellitus). Because ALS is a progressively deteriorating disease, addressing any potential endocrine co-morbidities in patients with this malady is quite important for decreasing the overall ALS-associated disease burden. Importantly, as this burden is estimated to increase globally in the decades to follow, in part because of an increasingly aging population, it is high time for future multi-center, multi-ethnic studies to assess the link between ALS and the endocrine system in significantly larger patient populations. Last, the psychosocial stress experienced by patients with ALS and its psycho-neuro-endocrinological sequelae, including hypothalamic-pituitaryadrenal dysregulation, should become an area of intensive study in the future.
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3.
Extracorporeal apheresis therapy for Alzheimer disease-targeting lipids, stress, and inflammation.
Bornstein, SR, Voit-Bak, K, Rosenthal, P, Tselmin, S, Julius, U, Schatz, U, Boehm, BO, Thuret, S, Kempermann, G, Reichmann, H, et al
Molecular psychiatry. 2020;(2):275-282
Abstract
Current therapeutic approaches to Alzheimer disease (AD) remain disappointing and, hence, there is an urgent need for effective treatments. Here, we provide a perspective review on the emerging role of "metabolic inflammation" and stress as a key factor in the pathogenesis of AD and propose a novel rationale for correction of metabolic inflammation, increase resilience and potentially slow-down or halt the progression of the neurodegenerative process. Based on recent evidence and observations of an early pilot trial, we posit a potential use of extracorporeal apheresis in the prevention and treatment of AD. Apolipoprotein E, lipoprotein(a), oxidized LDL (low density lipoprotein)'s and large LDL particles, as well as other proinflammatory lipids and stress hormones such as cortisol, have been recognized as key factors in amyloid plaque formation and aggravation of AD. Extracorporeal lipoprotein apheresis systems employ well-established, powerful methods to provide an acute, reliable 60-80% reduction in the circulating concentration of these lipid classes and reduce acute cortisol levels. Following a double-membrane extracorporeal apheresis in patients with AD, there was a significant reduction of proinflammatory lipids, circulating cytokines, immune complexes, proinflammatory metals and toxic chaperones in patients with AD. On the basis of the above, we suggest designing clinical trials to assess the promising potential of such "cerebropheresis" treatment in patients with AD and, possibly, other neurodegenerative diseases.
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Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension.
Piaditis, GP, Kaltsas, G, Markou, A, Chrousos, GP
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(12):827-833
Abstract
Primary hyperaldosteronism (PA) is a well-known cause of hypertension although its exact prevalence amongst patients with apparent essential hypertension has been a matter of debate. A number of recent studies have suggested that mild forms of PA may be relatively common taking into consideration factors that were previously either overestimated or ignored when developing diagnostic tests of PA and when applying these tests into normotensive individuals. The performance characteristics and diagnostic accuracy of such tests are substantially increased when the adrenocorticotrophin effect, inappropriate potassium levels and their application in carefully selected normotensive individuals are considered. In the present review, we critically analyze these issues and provide evidence that several, particularly mild, forms of PA can be effectively identified exhibiting potentially important clinical implications.
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Stress management for headaches in children and adolescents: A review and practical recommendations for health promotion programs and well-being.
Bougea, A, Spantideas, N, Chrousos, GP
Journal of child health care : for professionals working with children in the hospital and community. 2018;(1):19-33
Abstract
Stress is considered to be the most common factor reported to trigger headaches in children and adolescents. Although tension-type headache and migraine are the two most common types of headache in children and adolescents, they are often untreated, ignoring their stressful background. We provide a narrative review of the available evidence for health-care professionals involved in stress-related headache management and health promotion programs. An integrative plan is delivered through lifestyle improvement and biopsychosocial modifying stress response techniques. Healthy dietary choices, sleep hygiene, and regular exercise, although limited, are effective for young sufferers. Biopsychosocial therapies such as relaxation, biofeedback, hypnosis, yoga, cognitive behavioral therapy, and acupuncture focus at stress physiological and behavioral relief. Our purpose is to suggest a stress-related headache management to empower children to make healthy choices in order to improve their lifelong well-being and quality of life. We aim to authorize relationship between nurses and other health-care providers with background knowledge around stress management for pediatric headache populations.
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6.
Chronic stress and body composition disorders: implications for health and disease.
Stefanaki, C, Pervanidou, P, Boschiero, D, Chrousos, GP
Hormones (Athens, Greece). 2018;(1):33-43
Abstract
Recent studies have suggested that body composition is key to health and disease. First, fat tissue is a complex, essential, and highly active metabolic and endocrine organ that responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine, metabolic, and immune functions. Second, skeletal muscle mass is an important predictor of health in adult life, while severe mass loss has been associated with the frailty of old age. Studies have shown that skeletal muscle is also an important endocrine organ that secretes factors with autocrine, paracrine, or endocrine actions, which have been associated with inflammatory processes. Third, the bone is also a systemic endocrine regulator playing a pivotal role in health and disease. Finally, proper hydration in humans has been neglected as a health factor, especially in adults. Chronic stress and stress hormone hypersecretion alone or associated with distinct disorders, such as anxiety, depression, obesity, metabolic syndrome, autoimmune disorders, type 2 diabetes mellitus, and polycystic ovary syndrome (PCOS), have been associated with psychological and somatic manifestations, typically, increased fat mass, osteosarcopenia/frailty, cellular dehydration, and chronic systemic inflammation. This review aims to provide new insights into the newly developed concept of stress-related osteosarcopenic obesity and its prevention.
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7.
Vitamin D and cardiovascular risk among adults with obesity: a systematic review and meta-analysis.
Manousopoulou, A, Al-Daghri, NM, Garbis, SD, Chrousos, GP
European journal of clinical investigation. 2015;(10):1113-26
Abstract
BACKGROUND Obesity is a risk factor for both vitamin D deficiency and cardiovascular disease. A link between vitamin D status optimisation and improved cardiometabolic profile among adults with obesity could inform public health initiatives. METHODS PubMed, Embase and Web of Science were searched for interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors (anthropometric measures, lipid profile, blood pressure, glucose tolerance) among nondiabetic adults with obesity. RESULTS Seventeen publications reporting results from 11 different studies were included. Number of participants ranged from 34 to 1179 subjects. Duration was between 6 weeks and 4 years. Vitamin D was administered as a supplement in ten studies (1000 IU daily to 120 000 IU fortnightly). In one study, participants were advised to increase sunlight exposure and dietary vitamin D intake. The random and fixed-effects meta-analysis showed that vitamin D significantly increased systolic blood pressure and LDL-C levels. The fixed-effects model also indicated a significant decrease in triglyceride levels, which was not evident using the random-effects model. Caution should be given to these results given the small number of studies used and the high heterogeneity between studies for the two latter outcomes. Additionally, a subset of eligible studies with compatible data presentation was included in the meta-analysis. CONCLUSION This systematic review highlights a paucity of interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors among otherwise healthy adults with obesity. Large-scale studies at pharmacologically relevant doses and with sufficient duration are warranted.
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Conceptual framework of a simplified multi-dimensional model presenting the environmental and personal determinants of cardiometabolic risk behaviors in childhood.
Moschonis, G, Tsoutsoulopoulou, K, Efstathopoulou, E, Tsirigoti, L, Lambrinou, CP, Georgiou, A, Filippou, C, Lidoriki, I, Reppas, K, Androutsos, O, et al
Expert review of cardiovascular therapy. 2015;(6):673-92
Abstract
Clinical manifestations of cardiometabolic risk (CMR) may be set early in childhood due to unfavorable behaviors or lifestyle patterns related to diet and physical activity. Several factors may determine the adoption of such lifestyle-related behaviors, which researchers have tried to cluster under certain frameworks or models. In this context, the framework developed and proposed by this review gathers all the present knowledge regarding these determining factors to date and groups them into three main categories related to personal characteristics and the social and physical environment. Based on the proposed framework, a large variety of personal, social and physical environmental factors can positively or negatively influence CMR-related behaviors (either directly or indirectly via their interrelations), thus leading to decreased or increased risk, respectively. This framework could be of great value to public health policy makers and legislators for designing and implementing interventional programs tailored to the needs of susceptible population groups who are most in need for such initiatives. Targeting the correlates as potential determinants of CMR-related behaviors, and not just on the behaviors themselves, has been shown previously to be the most effective approach for tackling health issues related to CMR starting from early life stages.
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9.
Influences on adherence to diet and physical activity recommendations in women and children: insights from six European studies.
Inskip, H, Baird, J, Barker, M, Briley, AL, D'Angelo, S, Grote, V, Koletzko, B, Lawrence, W, Manios, Y, Moschonis, G, et al
Annals of nutrition & metabolism. 2014;(3-4):332-9
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Abstract
BACKGROUND Across Europe, poor health behaviours are associated with increased risks of non-communicable diseases. There is particular concern about young women, children and families, not least as health behaviours operating before and during pregnancy and in early postnatal life may have profound long-term consequences for children's health. Using findings drawn from 7 European countries, we aimed to identify barriers to the implementation and uptake of dietary and physical activity recommendations, and to consider how best to achieve changes in mothers' behaviours and thereby improve the adoption of health recommendations. Six studies across the 7 countries were used for this narrative synthesis of findings. KEY MESSAGES A woman's education has a strong influence on her own and her children's health behaviours. Women's diets vary across ethnic groups and according to number of children, but psychological factors, such as self-efficacy and sense of control, which may be amenable to modification, are powerful, too, particularly in women with lower educational attainment. Maternal influences on children's behaviours are strong. Differences exist in infant feeding across countries, and there are apparent urban/rural differences in children's diets and physical activity. CONCLUSIONS Interventions are needed before, as well as during, pregnancy to improve the diets of families with young children. Interventions to address psychological barriers to eating well and being more active are indicated.
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Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder.
Charmandari, E, Kino, T, Ichijo, T, Chrousos, GP
The Journal of clinical endocrinology and metabolism. 2008;(5):1563-72
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Abstract
CONTEXT Primary generalized glucocorticoid resistance is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. We review the clinical aspects, molecular mechanisms, and implications of this disorder. EVIDENCE ACQUISITION We conducted a systematic review of the published, peer-reviewed medical literature using MEDLINE (1975 through February 2008) to identify original articles and reviews on this topic. EVIDENCE SYNTHESIS We have relied on the experience of a number of experts in the field, including our extensive personal experience. CONCLUSIONS The clinical spectrum of primary generalized glucocorticoid resistance is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue, and/or mineralocorticoid excess. The molecular basis of the condition has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction and reduce tissue sensitivity to glucocorticoids. A consequent increase in the activity of the hypothalamic-pituitary-adrenal axis compensates for the reduced sensitivity of peripheral tissues to glucocorticoids at the expense of ACTH hypersecretion-related pathology. The study of functional defects of natural hGR mutants enhances our understanding of the molecular mechanisms of hGR action and highlights the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology.