Autoimmune primary adrenal insufficiency -current diagnostic approaches and future perspectives

The adrenal glands are small endocrine glands located on top of each kidney, producing hormones regulating important functions in our body like metabolism and stress. There are several underlying causes for adrenal insufficiency, where an autoimmune attack by the immune system is the most common cause. A number of genes are known to confer early onset adrenal disease in monogenic inheritance patterns, usually genetic encoding enzymes of adrenal steroidogenesis. Autoimmune primary adrenal insufficiency is usually a polygenic disease where our information recently has increased due to genome association studies. In this review, we go through the physiology of the adrenals before explaining the different reasons for adrenal insufficiency with a particular focus on autoimmune primary adrenal insufficiency. We will give a clinical overview including diagnosis and current treatment, before giving an overview of the genetic causes including monogenetic reasons for adrenal insufficiency and the polygenic background and inheritance pattern in autoimmune adrenal insufficiency. We will then look at the autoimmune mechanisms underlying autoimmune adrenal insufficiency and how autoantibodies are important for diagnosis. We end with a discussion on how to move the field forward emphasizing on the clinical workup, early identification, and potential targeted treatment of autoimmune PAI

Interferon autoantibodies as signals of a sick thymus

Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function magnitude, and adaptive immunity to fight infections, and they must therefore be tightly regulated. It has become increasingly evident that thymic irregularities and mutations in immune genes affecting thymic tolerance can lead to the production of IFN-I autoantibodies (autoAbs). Whether these biomarkers affect the immune system or tissue integrity of the host is still controversial, but new data show that IFN-I autoAbs may increase susceptibility to severe disease caused by certain viruses, including SARS-CoV-2, herpes zoster, and varicella pneumonia. In this article, we will elaborate on disorders that have been identified with IFN-I autoAbs, discuss models of how tolerance to IFN-Is is lost, and explain the consequences for the host

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: a protocol for a systematic review of human experimental studies

BACKGROUND: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s across multiple sectors exposing large proportions of the population. This fact has raised concerns related to the potential consequences to people's health. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF and has carried out an international survey amongst experts, who have identified six priority topics to be further addressed through systematic reviews, whereof the effects on symptoms is one of them. We report here the systematic review protocol of experimental studies in humans assessing the effects of RF-EMF on symptoms. OBJECTIVE: Our objectives are to assess the effects of exposure to electromagnetic fields (compared to no or lower exposure levels) on symptoms in human subjects. We will also assess the accuracy of perception of presence of exposure in volunteers with and without idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF). ELIGIBILITY CRITERIA: We will search relevant literature sources (e.g. the Web of Science, Medline, Embase, Epistemonikos) for randomized trials (comparing at least two arms) and randomised crossover trials of RF-EMF exposure that have assessed the effects on symptoms. We will also include studies that have measured the accuracy of the perception of the presence or absence of exposure. We will include studies in any language. STUDY APPRAISAL AND SYNTHESIS: Studies will be assessed against inclusion criteria by two independent reviewers. Data on study characteristics, participants, exposure, comparators and effects will be extracted using a specific template for this review, by two independent reviewers. Discrepancies will be solved by consensus. Risk of bias (ROB) will be assessed using the ROB Rating Tool for Human and Animal Studies and the level of confidence in the evidence of the exposure-outcome relations will be assessed using the GRADE approach. For the perception studies, we will use adapted versions of the ROB tool and GRADE assessment. Where appropriate, data will be combined using meta-analytical techniques

Self-Guided Multimedia Stress Management and Resilience Training for Flight Controllers

Stress and anxiety-related problems are among the most common and costly behavioral health problems in society, and for those working in operational environments (i.e. astronauts, flight controllers, military) this can seriously impact crew performance, safety, and wellbeing. Technology-based interventions are effective for treating behavioral health problems, and can significantly improve the delivery of evidence-based health care. This study is evaluating the effectiveness, usefulness, and usability of a self-guided multimedia stress management and resilience training program in a randomized controlled trial (RCT) with a sample of flight controllers at Johnson Space Center. The intervention, SMART-OP (Stress Management and Resilience Training for Optimal Performance), is a six-session, cognitive behavioral-based computer program that uses self-guided, interactive activities to teach skills that can help individuals build resilience and manage stress. In a prior RCT with a sample of stressed but otherwise healthy individuals, SMART-OP reduced perceived stress and increased perceived control over stress in comparison to an Attention Control (AC) group. SMART-OP was rated as "highly useful" and "excellent" in usability and acceptability. Based on -amylase data, individuals in SMART-OP recovered quicker and more completely from a social stress test as compared to the AC group [1]. In the current study, flight controllers are randomized either to receive SMART-OP training, or to a 6-week waitlist control period (WLC) before beginning SMART-OP. Eligible participants include JSC flight controllers and instructors without any medical or psychiatric disorder, but who are stressed based on self-report. Flight controllers provide a valid analog sample to astronauts in that they work in an operational setting, use similar terminology to astronauts, are mission-focused, and work under the same broader work culture. The study began in December 2014, and to date 79 flight controllers and instructors have expressed interest in the study, 49 of those were cleared for participation, we have screened 44 for eligibility, and 23 have met inclusion criteria. Recruitment is ongoing and the study will continue until December 2016. Outcome measures include perceived stress, perceived control over stress, resilience, mood, personality, emotion regulation, sleep, health behaviors, and psychophysiological data such as 24-hour heart rate, alpha amylase, and urinary and salivary cortisol. We are also collecting user feedback such as usability, working alliance, usefulness, and treatment credibility

Effect of lactation stage and concurrent pregnancy on milk composition in the bottlenose dolphin

Although many toothed whales (Cetacea: Odontoceti) lactate for 2–3 years or more, it is not known whether milk composition is affected by lactation stage in any odontocete species. We collected 64 pooled milk samples spanning 1–30 months postpartum from three captive bottlenose dolphins Tursiops truncatus. Milks were assayed for water, fat, crude protein (TN × 6.38) and sugar; gross energy was calculated. Ovulation and pregnancy were determined via monitoring of milk progesterone. Based on analysis of changes in milk composition for each individual dolphin, there were significant increases (P<0.05) in fat (in all three dolphins) and crude protein (in two of three), and a decrease (P<0.05) in water (in two of three) over the course of lactation, but the sugar content did not change. In all three animals, the energy content was positively correlated with month of lactation, but the percentage of energy provided by crude protein declined slightly but significantly (P<0.05). At mid-lactation (7–12 months postpartum, n=17), milk averaged 73.0±1.0% water, 12.8±1.0% fat, 8.9±0.5% crude protein, 1.0±0.1% sugar, 1.76±0.09 kcal g−1 (=7.25 kJ g−1) and 30.3±1.3% protein:energy per cent. This protein:energy per cent was surprisingly high compared with other cetaceans and in relation to the growth rates of calves. Milk progesterone indicated that dolphins ovulated and conceived between 413 and 673 days postpartum, following an increase in milk energy density. The significance of these observed compositional changes to calf nutrition will depend on the amounts of milk produced at different stages of lactation, and how milk composition and yield are influenced by sampling procedure, maternal diet and maternal condition, none of which are known

Guidelines for limiting exposure to electromagnetic fields (100 kHz to 300 GHz)

Radiofrequency electromagnetic fields (EMFs) are used to enable a number of modern devices, including mobile telecommunications infrastructure and phones, Wi-Fi, and Bluetooth. As radiofrequency EMFs at sufficiently high power levels can adversely affect health, ICNIRP published Guidelines in 1998 for human exposure to time-varying EMFs up to 300 GHz, which included the radiofrequency EMF spectrum. Since that time, there has been a considerable body of science further addressing the relation between radiofrequency EMFs and adverse health outcomes, as well as significant developments in the technologies that use radiofrequency EMFs. Accordingly, ICNIRP has updated the radiofrequency EMF part of the 1998 Guidelines. This document presents these revised Guidelines, which provide protection for humans from exposure to EMFs from 100 kHz to 300 GHz

Superconductivity in Cu_xTiSe_2

Charge density waves (CDWs) are periodic modulations of the conduction electron density in solids. They are collective states that arise from intrinsic instabilities often present in low dimensional electronic systems. The layered dichalcogenides are the most well-studied examples, with TiSe_2 one of the first CDW-bearing materials known. The competition between CDW and superconducting collective electronic states at low temperatures has long been held and explored, and yet no chemical system has been previously reported where finely controlled chemical tuning allows this competition to be studied in detail. Here we report how, upon controlled intercalation of TiSe_2 with Cu to yield Cu_xTiSe_2, the CDW transition is continuously suppressed, and a new superconducting state emerges near x = 0.04, with a maximum T_c of 4.15 K found at x = 0.08. Cu_xTiSe_2 thus provides the first opportunity to study the CDW to Superconductivity transition in detail through an easily-controllable chemical parameter, and will provide new insights into the behavior of correlated electron systems.Comment: Accepted to Nature Physic

Light-emitting diodes (LEDS): Implications for safety

Since the original ICNIRP Statement was published in 2000, there have been significant improvements in the efficiency and radiance (i.e., optical radiation emission) of LEDs. The most important improvement is the development of 'white' LEDs that can be used as general lighting sources, which are more efficient than traditional lighting sources. LEDs emitting in the ultraviolet wavelength region have also become available and have made their way into consumer products. All these changes have led to a rise in concern for the safety of the optical radiation emissions from LEDs. Several in vitro and animal studies have been conducted, which indicate that blue and white LEDs can potentially cause retinal cell damage under high irradiance and lengthy exposure conditions. However, these studies cannot be directly extrapolated to normal exposure conditions for humans, and equivalent effects can also be caused by the optical radiation from other light sources under extreme exposure conditions. Acute damage to the human retina from typical exposure to blue or white LEDs has not been demonstrated. Concern for potential long-term effects, e.g. age-related macular degeneration (AMD), remains based on epidemiological studies indicating a link between high levels of exposure to sunlight and AMD. When evaluating the optical radiation safety of LEDs, it has now been established that published safety standards for lamps, not lasers, should be applied. Thus far, the only clear, acute adverse health effects from LEDs are those due to temporal light modulation (including flicker). Glare can also create visual disturbances when LED light fixtures are not properly designed. Further research is needed on potential health effects from short- and long-term exposure to new and emerging lighting technologies

Principles for non-ionizing radiation protection

In this statement, the International Commission on Non-Ionizing Radiation Protection (ICNIRP) presents its principles for protection against adverse health effects from exposure to non-ionizing radiation. These are based upon the principles for protection against ionizing radiation of the International Commission for Radiological Protection (ICRP) in order to come to a comprehensive and consistent system of protection throughout the entire electromagnetic spectrum. The statement further contains information about ICNIRP and the processes it uses in setting exposure guidelines

Gaps in knowledge relevant to the “guidelines for limiting exposure to time-varying electric and magnetic fields (1 Hz-100 kHz)"

Sources of low-frequency fields are widely found in modern society. All wires or devices carrying or using electricity generate extremely low frequency (ELF) electric fields (EFs) and magnetic fields (MFs), but they decline rapidly with distance to the source. High magnetic flux densities are usually found in the vicinity of power lines and close to equipment using strong electrical currents, but can also be found in buildings with unbalanced return currents, or indoor transformer stations. For decades, epidemiological as well as experimental studies have addressed possible health effects of exposure to ELF-MFs. The main goal of ICNIRP is to protect people and the environment from detrimental exposure to all forms of non-ionizing radiation (NIR). To this end, ICNIRP provides advice and guidance by developing and disseminating exposure guidelines based on the available scientific research. Research in the low-frequency range began more than 40 years ago, and there is now a large body of literature available on which ICNIRP set its protection guidelines. A review of the literature has been carried out to identify possible relevant knowledge gaps, and the aim of this statement is to describe data gaps in research that would, if addressed, assist ICNIRP in further developing guidelines and setting revised recommendations on limiting exposure to electric and magnetic fields. It is articulated in two parts: the main document, which reviews the science related to LF data gaps, and the annex, which explains the methodology used to identify the data gaps