Background Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuroendocrine equivalent of the systemic hypothalamic-pituitary-adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used corticotropin-releasing hormone (CRH), which triggers the HPA axis, to induce a stress response in human ex vivo male AGA HFs. Caffeine is known to reverse testosterone-mediated hair growth inhibition in the same hair organ culture model. Objectives To investigate whether caffeine would antagonize CRH-mediated stress in these HFs. Methods HFs from balding vertex area scalp biopsies of men affected by AGA were incubated with CRH (10 À7 mol L À1) with or without caffeine (0Á001% or 0Á005%). Results Compared to controls, CRH significantly enhanced the expression of catagen-inducing transforming growth factor-b2 (TGF-b2) (P < 0Á001), CRH receptors 1 and 2 (CRH-R1/2) (P < 0Á01), adrenocorticotropic hormone (ACTH) (P < 0Á001) and melanocortin receptor 2 (MC-R2) (P < 0Á001), and additional stressassociated parameters, substance P and p75 neurotrophin receptor (p75 NTR). CRH inhibited matrix keratinocyte proliferation and expression of anagen-promoting insulin-like growth factor-1 (IGF-1) and the pro-proliferative nerve growth factor receptor NGF-tyrosine kinase receptor A (TrkA). Caffeine significantly counteracted all described stress effects and additionally enhanced inositol trisphosphate receptor (IP 3-R), for the first time detected in human HFs. Conclusions These findings provide the first evidence in ex vivo human AGA HFs that the stress mediator CRH induces not only a complex intrafollicular HPA response, but also a non-HPA-related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss,
Tetrabromobisphenol A (TeBBPA) is a four-meta-brominated variant of bisphenol A (BPA) and is one of the most commonly used brominated flame retardants worldwide. We compared the estrogenic potency of TeBBPA, BPA and the brominated analogs mono- (MBBPA), di- (DBBPA), and tribromobisphenol A (TrBBPA) in the estrogen-dependent human breast cancer cell line MCF-7. All of the compounds competed with 17beta-estradiol for binding to the estrogen receptor, although the affinity of the test chemicals to the estrogen receptor was much lower than that of 17beta-estradiol. TrBBPA and TeBBPA showed a considerably lower access to the estrogen receptors within intact MCF-7 cells incubated in 100% serum compared to incubation in serum-free medium, indicating a strong binding to serum proteins. BPA, MBBPA, and DBBPA showed only a slightly reduced access to the receptors. All of the test compounds induced proliferation in MCF-7 cells, the potential decreasing with increasing number of bromo-substitutions. TeBBPA did not induce maximal cell growth, indicating cytotoxic effects at high concentrations. BPA and the brominated analogs, except TeBBPA, induced progesterone receptor and pS2 to the same extent as 17beta-estradiol, although at much higher concentrations. Our studies demonstrate that compared to 17beta-estradiol, BPA and the brominated analogs have much lower estrogenic potencies for all of the endpoints tested, TeBBPA being the least estrogenic compound.
With regard to the guidelines of the European Resuscitation Council, we are convinced that during cardiac arrest supraglottic airway devices should be used by emergency personnel unfamiliar with endotracheal intubation.
IntroductionThere is considerable uncertainty about the reproducibility of the various instruments used to measure dyspnea, their ability to reflect changes in symptoms, whether they accurately reflect the patient's experience and if its evolution is similar between acute heart failure syndrome patients and nonacute heart failure syndrome patients. URGENT was a prospective multicenter trial designed to address these issues. Methods Patients were interviewed within 1 hour of first physician evaluation, in the emergency department or acute care setting, with dyspnea assessed by the patient using both a five-point Likert scale and a 10-point visual analog scale (VAS) in the sitting (60º) and then supine (20º) position if dyspnea had not been considered severe or very severe by the sitting versus decubitus dyspnea measurement. Results Very good agreements were found between the five-point Likert and VAS at baseline (0.891, P <0.0001) and between changes (from baseline to hour 6) in the five-point Likert and in VAS (0.800, P <0.0001) in acute heart failure (AHF) patients. Lower agreements were found when changes from baseline to H6 measured by Likert or VAS were compared with the seven-point comparative Likert (0.512 and 0.500 respectively) in AHF patients. The worse the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours; this relationship is stronger when dyspnea is measured with VAS (Spearman's rho coefficient = 0.672) than with the five-point Likert (0.272) (both P <0.0001) in AHF patients. By the five-point Likert, only nine patients (3% (1% to 5%)) reported an improvement in their dyspnea, 177 (51% (46% to 57%)) had no change, and 159 (46% (41% to 52%)) reported worse dyspnea supine compared with sitting up in AHF patients. The PDA test with VAS was markedly different between AHF and non-AHF patients. Conclusions Both clinical tools five-point Likert and VAS showed very good agreement at baseline and between changes from baseline to tests performed 6 hours later in AHF patients. The PDA test with VAS was markedly different between AHF and non-AHF patients. Dyspnea is improved within 6 hours in more than threequarters of the patients regardless of the tool used to measure the change in dyspnea. The greater the dyspnea at admission, the greater the amplitude of improvement in the first 6 hours. Introduction Endotracheal intubation (ETI) engages the patient's life and demands a good experience. A preliminary prospective study has shown in one hospital that emergency physicians (EPs) rarely performed ETI. Do the EPs in Ile de France (Paris region) have sufficient experience and regular training to realise this procedure safely in the emergency room (ER)? Methods We conducted a descriptive telephone-based questionnaire study to assess EPs' endotracheal intubation skills through all ERs in Ile de France public hospitals. A questionnaire was completed by the investigator during a 10-minute telephone call with at least one EP in each ER. The structure of hospitals, number of ETIs perform...
The COVID-19 pandemic has prompted severe restrictions on everyday life to curb the spread of infections. For example, teaching at universities has been switched to an online format, reducing students' opportunities for exchange, and social interaction. Consequently, their self-reported mental health has significantly decreased and there is a pressing need to elucidate the underlying mechanisms—ideally considering not only data collected during the pandemic, but also before. One hundred seventeen German university students aged 18-27 were assessed for known resilience factors (optimism, self-care, social support, generalized self-efficacy) and subsequently completed surveys on stress experiences and mental health every 3 months over a period of 9 months before the outbreak of the pandemic and once during the first lockdown in Germany. For each timepoint before the pandemic, we regressed participants' mental health against the reported stressor load, such that the resulting residuals denote better or worse than expected outcomes, i.e., the degree of resilient functioning. We then tested whether different expressions in the resilience factors were predictive of distinct resilient functioning trajectories, which were identified through latent class growth analysis. Finally, we investigated whether trajectory class, resilience factors, and perceived stress predicted resilience during the pandemic. Results show rather stable resilient functioning trajectories, with classes differing mainly according to degree rather than change over time. More self-care was associated with a higher resilient functioning trajectory, which in turn was linked with the most favorable pandemic response (i.e., lower perceived stress and more self-care). Although findings should be interpreted with caution given the rather small sample size, they represent a rare examination of established resilience factors in relation to resilience over an extended period and highlight the relevance of self-care in coping with real-life stressors such as the pandemic.
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