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

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

Health-care professionals' assessment of a person-centred intervention to empower self-management and health across chronic illness: Qualitative findings from a process evaluation study.

BACKGROUND: Person-centred care (PCC) empowers patients to manage their chronic illness and promote their health in accordance with their own beliefs, values and preferences. Drawing on health-care professional's (HCP's) experiences implementing an empowerment-focused, person-centred intervention called the Bodyknowledging Program (BKP), we undertook a process evaluation that aimed to assess the impact on patient health and well-being. METHODS: We used individual in-depth interviews and semi-structured focus groups comprising n = 8 interprofessional HCP who facilitated intervention sessions with n = 58 patients situated in Norwegian specialist care sites. Content analysis was used to analyse the data and summarize major themes. RESULTS: Health-care professional interviews revealed four main ways in which the intervention operated in support of health-related patient outcomes: (i) addressing the whole person; (ii) hope and affirmation; (iii) expanding recovery; and (iv) social support and revitalized relationships. The intervention provided new tools for patients to understand the social, emotional and physical impact of their illness. Health-care professional reported new insights to facilitate patient engagement and to promote patients' health. CONCLUSIONS: The Bodyknowledging Program facilitated patient engagement through the promotion of patient-centred care while developing the patients' ability to exploit their own resources for effectively managing their health within illness. The process evaluation supported the underlying theoretical basis of the intervention and was suggestive of its potential transferability elsewhere

Health Care Professionals' Experiences of Facilitating Patient Activation and Empowerment in Chronic Illness using a Person-Centered and Strengths-Based Self-Management Program.

OBJECTIVE: Patients with chronic illness who are empowered and activated are more likely to engage in self-management in order to stabilise their condition and enhance their quality of life. This study aimed to explore Health Care Professional's (HCP) assessment of a person-centered intervention called 'The Bodyknowledging Program' (BKP) for the facilitation of empowerment and patient activation in the context of chronic illness. METHODS: This study employed a qualitative process evaluation after programme completion. Data was collected through focus-groups and individual interviews with HCPs and content analysis was used in the analysis. RESULTS: Four themes were identified: 1) Shifts towards the patient-perspective, 2) The value of a patient-centered conceptual framework, 3) Patient activation through dialogue based support and 4) Challenging competencies. Discussion: This study introduces 'The Bodyknowledging Program' as a useful tool to uncover patients' needs and to activate and empower them to take more responsibility for their health through self-care management. The usability of the new intervention depends on HCP's ability to develop their counselling skills and changing their approach towards utilising patients' individual resources in the promotion of their health

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

Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 μg/m(3) and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I(2) = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence

Validation of a new assay for alpha-synuclein detection in cerebrospinal fluid

BACKGROUND: Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein. METHODS: This novel ELISA uses commercially available antibodies and is based on electrochemiluminescence technology. The assay protocol is straightforward, with short and simple incubation steps, and requires only small amounts of CSF. We validated this assay for precision, parallelism, dilution linearity, specificity, and spike recovery. We further compared it to the newly validated α-synuclein assay from BioLegend by analyzing a set of 50 CSF samples with both assays. RESULTS: The new assay quantifies α-synuclein in CSF with a lower limit of detection of 36.3 pg/mL and shows no cross-reactivity with human β- and γ-synuclein. Results of dilution linearity, parallelism, spike recovery, and precision classify this assay as well suited for α-synuclein detection in human CSF samples. CONCLUSIONS: We present a novel assay based on freely available components to quantify total α-synuclein in CSF as an additional method for α-synuclein as a biomarker in neurodegenerative diseases. The assay convinces with its simple and convenient protocol paired with high sensitivity

Исследование тепловых характеристик в виброаппарате - утилизаторе отработавшего топлива АЗС

Purpose: Self-management is crucial for effective COPD management. This study aimed at identifying associations between self-management and sociodemographic characteristics, clinical characteristics, and symptom burden in people with COPD.Patients and methods: In this cross-sectional study with 225 participants diagnosed with COPD grades II&ndash;IV, multiple linear regression analysis was conducted, using sociodemographic and clinical characteristics and symptom burden (COPD Assessment Test) as the independent variables and the eight self-management domains of the Health Education Impact Questionnaire (heiQ) as the outcome variables.Results: Higher symptom burden was significantly associated with worse scores in all self-management domains (p&lt;0.003), except for self-monitoring and insight (p=0.012). Higher disease severity (p=0.004) and numbers of comorbidities (p&lt;0.001) were associated with more emotional distress, and women scored higher than men on positive and active engagement in life (p=0.001). Higher score in pack-years smoking was associated with lower score in health-directed activities (p=0.006) and self-monitoring and insight (p&lt;0.001), and participation in organized physical training was associated with higher score in health-directed activities (p&lt;0.001). The final models explained 3.7%&ndash;31.7% of variance (adjusted R2) across the eight heiQ scales.Conclusion: A notable finding of this study was that higher symptom burden was associated with worse scores in all self-management domains, except for self-monitoring and insight. In addition, sex, disease severity, comorbidity, pack-years smoking, and participation in organized physical training were associated with one or two self-management domains. The study contributes to improved understanding of self-management in COPD. However, the explained variance levels indicate that more research needs to be done to uncover what else explains self-management domains in COPD.<br /

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