In the LEW/N rat model, a decreased hypothalamic-pituitary-adrenal (HPA) axis response to inflammatory and immune mediators confers susceptibility to the development of a variety of inflammatory and immune diseases, including experimental allergic encephalomyelitis. In humans with optic neuritis, early intervention with steroids is associated with a decrease in the number of patients who go on to develop multiple sclerosis (MS). The current study was designed to determine whether patients with MS show evidence of a hypoactive HPA axis. Thirteen patients with MS were studied at baseline and with provocative tests of HPA axis function [ovine CRH, arginine vasopressin (AVP), and ACTH stimulation]. Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression. Patients with MS also showed blunted ACTH responses to AVP stimulation and normal cortisol responses to high and low dose ACTH stimulation. Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis. These data do not support a role for hypocortisolism in MS once the disease is established.
Abstract Background The epidemiology of alopecia areata (AA) is well documented in adults but has not been studied adequately in children. Objective To evaluate the clinical and epidemiological profile of AA in children and assess the significance of thyroid screening. Methods One hundred and fifty‐seven children (83 boys, 74 girls, aged 1–16 years) who visited our clinic with a first episode of AA from 1996 to 2000 were retrospectively studied. One hundred children served as clinical controls. Results The age of peak incidence of AA was 0–5 years. The youngest child was 1 year old. In the majority of the cases (131/157, 83.4%) the disease was mild or moderate (less than 50% hair loss). In 15 patients (9.5%), AA was preceded by a stressful event. Five patients had a personal history of autoimmune disease (3.2 vs. 5% of the controls, ( P = not significant [NS]) while 18 patients had a personal history of atopy (11.4 vs. 18% of the controls, P = NS). Twenty‐one patients had a family history of autoimmune disease other than thyroiditis (13.4 vs. 5% of the controls, P = 0.04), while 23 patients had a family history of thyroid disorder (14.6 vs. 3% of the controls, P = 0.006). In eight patients (5%) subclinical hypothyroidism of autoimmune aetiology (Hashimoto's thyroiditis) was revealed at the time of investigation. Six out of the eight patients with Hashimoto's thyroiditis had a family history of thyroid disorder, which was statistically significant when compared to AA patients without thyroiditis ( P < 0.001). The severity of AA was associated with early age of onset of the disease ( P = 0.02). Conclusion The age of peak incidence of AA in children is 0–5 years. Children with AA have an increased family history of autoimmunity, and, among children with a first episode and short duration of AA (< 6 months), thyroid screening might be restricted in those with a positive family history of thyroid disorder. Thyroid screening should be routinely performed in all children with long‐standing AA.
Epicurus used an empirical and sensualistic approach to knowledge, creating a consistent, naturalistic, pragmatic and consequentialistic philosophy. The scientific observations of the last centuries have confirmed the basic principles of Epicurean physics, as well the psychotherapeutic approach of Epicurean ethics, which fits human nature. We know from the work “On Frank Criticism” of Epicurean philosopher Philodemus of Gadara, that the teaching methodology of Epicureans included psychoeducational counseling through therapeutic criticism based on friendly freedom of speech and aiming at τῆς ψυχῆς θεραπείαν (psychotherapy) and at knowledge of maintaining mental health and well-being. The Epicureans called εὐστάθεια (eustatheia, “stability”) the psychosomatic balance (τὸ τῆς σαρκὸς καὶ ψυχῆς εὐσταθὲς κατάστημα), which today we call homeostasis (ὁμοιόστασις), and considered it the basis of true happiness. They recognized empirically the stress that disturbed psychosomatic homeostasis as an agitation of the psyche or a painful feeling of the body and used a number of mental and affective techniques (including the tetrapharmakos) to manage stress at its onset, so that it does not evolve into the particularly troublesome conditions of anxiety and/or depression, which may become chronic psychosomatic disorders with significant social consequences. The article discusses the relation of the main ethical teachings of Epicurus with the biological basis of human brain functions and with the management of stress by cognitive and behavioral psychotherapy.
Blast-loaded structures are presently assessed and designed following a deterministic approach, where only a set of structural analyses under worst-case design scenarios are carried out in order to verify each limit state. As a rational alternative, a conditional probabilistic approach is introduced to offer comprehensive risk assessment and to allow the design with user-defined confidence in meeting performance targets in view of uncertainties. To simplify the probabilistic consideration of the uncertain parameters, the determination of the blast hazard and the structural response are decoupled into the evaluation of blast hazard curves and structural fragilities curves, respectively, by introducing a single conditioning intensity measure. This is chosen to be the impulse density, shown to be sufficient for impulse-governed scenarios, achieving a reduction of the computational effort by several orders of magnitude without introducing bias. Furthermore a problem-specific safety factor formulation is introduced to incorporate the influence of uncertainties in a simple manner, akin to current engineering practice. As a proof-of-concept test, a steel built-up blast resistant door is subjected to an accidental detonation of mortar rounds in a military facility. The equivalent single degree of freedom model is adopted in order to conduct the structural analyses, while detailed finite element analyses are carried out for validation. Finally, the conditional approach risk analysis on the steel door is compared against the results obtained through the comprehensive (probabilistic) unconditional approach, showing the validity of both the proposed intensity measure and safety factor formulation.
Onshore buried steel pipelines are vulnerable to fault rupture, where large ground displacements are imposed on the crossing pipe and thus protection measures are often necessary to avoid failure. A three-step methodology based on the framework of performance-based earthquake engineering is presented on assessing the effectiveness of protection measures against the consequences of strike-slip faulting on pipes. Firstly, the randomness of the fault movement is quantified, next the pipeline mechanical behavior is numerically assessed and finally the results are combined to extract the strain hazard curves, which are easy-to-handle engineering decision making tools. The various protection measures used in engineering practice or proposed in the literature are evaluated through the mean annual rate of exceeding strain values, also including a simple safety checking format at the strain level. Conclusions are extracted from the proposed assessment methodology on the efficiency of measures with reference to engineering practice and safety requirements of the pipeline operator.
Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of the quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological centre of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the keywords: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its aetiology. The angular and linear cephalometric measurements differ from the measurements of the average normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusions: The greater part of the existing literature regarding cephalometric measurements in short-statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature should be the focus of future studies. These quantitative data are required to potentially establish cut-off values for reference for genetic testing based on craniofacial phenotypes.
