抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

/pdf/protective-and-damaging-effects-of-stress-mediators-34e0m747fy.pdf

Protective and Damaging Effects of Stress Mediators

Attachment--and loss.

This meta-analysis reviews 208 laboratory studies of acute psychological stressors and tests a theoretical model delineating conditions capable of eliciting cortisol responses. Psychological stressors increased cortisol levels; however, effects varied widely across tasks. Consistent with the theoretical model, motivated performance tasks elicited cortisol responses if they were uncontrollable or characterized by social-evaluative threat (task performance could be negatively judged by others), when methodological factors and other stressor characteristics were controlled for. Tasks containing both uncontrollable and social-evaluative elements were associated with the largest cortisol and adrenocorticotropin hormone changes and the longest times to recovery. These findings are consistent with the animal literature on the physiological effects of uncontrollable social threat and contradict the belief that cortisol is responsive to all types of stressors.

http://anthro.vancouver.wsu.edu/media/Course_files/anth-260-edward-h-hagen/acute-stressors-and-cortisol-responses-a-theoretical-integration-and-synthesis-of-laboratory-research-1.pdf

Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research.

Diurnal cortisol rhythm and cognitive functioning in toddlers: The Generation R Study Nathalie S. Saridjan a b , Jens Henrichs a c , Jacqueline J. Schenk c , Vincent W. V. Jaddoe a d e , Albert Hofman e , Clemens Kirschbaum f , Frank C. Verhulst b & Henning Tiemeier b e a The Generation R Study Group, Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands b Department of Child and Adolescent Psychiatry , Erasmus MCSophia Children's Hospital , Rotterdam , the Netherlands c Department of Developmental Psychology , Tilburg University , Tilburg , the Netherlands d Department of Pediatrics , Erasmus MC-Sophia Children's Hospital , Rotterdam , the Netherlands e Department of Epidemiology , Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands f Department of Psychology , Technical University of Dresden , Dresden , Germany Published online: 08 Feb 2013.

Child Neuropsychology: A Journal on Normal and Abnormal Development in Childhood and Adolescence

While there are many different methods for peak detection, no automatic methods for marking peak boundaries to calculate area under the curve (AUC) and signal-to-noise ratio (SNR) estimation exist. An algorithm for the automation of liquid chromatography tandem mass spectrometry (LC-MS/MS) mass chromatogram quantification was developed and validated. Continuous wavelet transformation and other digital signal processing methods were used in a multi-step procedure to calculate concentrations of six different analytes. To evaluate the performance of the algorithm, the results of the manual quantification of 446 hair samples with 6 different steroid hormones by two experts were compared to the algorithm results. The proposed approach of automating mass chromatogram quantification is reliable and valid. The algorithm returns less nondetectables than human raters. Based on signal to noise ratio, human non-detectables could be correctly classified with a diagnostic performance of AUC = 0.95. The algorithm presented here allows fast, automated, reliable, and valid computational peak detection and quantification in LC- MS/MS.

Automating LC-MS/MS mass chromatogram quantification. Wavelet transform based peak detection and automated estimation of peak boundaries and signal-to-noise ratio using signal processing methods

https://doi.org/10.1016/j.psyneuen.2022.105919

What to do now that hypocortisol appears to be a predominant sign of long COVID?

Background: Cell deformability of all major blood cell types is increased in depressive disorders (DD). Furthermore, impaired glucocorticoid secretion is causally related to DD. Nevertheless, there are no longitudinal studies examining changes in glucocorticoid output and depressive symptoms regarding cell deformability in DD. Aim: To investigate, whether changes in depressive symptoms or hair glucocorticoids predict cell deformability in DD. Methods: In 136 individuals, depressive symptoms (PHQ-9) and hair glucocorticoids (cortisol and cortisone) were measured at timepoint one (T1), while one year later (T2) depressive symptoms and hair glucocorticoids were remeasured and additionally cell deformability of peripheral blood cells was assessed and DD status was determined by clinical interview. Results: Depression severity at T1 predicted higher cell deformability in monocytes and lymphocytes over the entire sample. Subjects with continuously high depressive symptoms at T1 and T2 showed elevated monocyte deformability as compared to subjects with low depressive symptoms. Depression severity at T1 of subjects with a lifetime persistent depressive disorder (PDD) was associated with elevated monocyte, neutrophil, and granulo-monocyte deformability. Depression severity at T1 of subjects with a 12-month PDD was positively associated with monocyte deformability. Furthermore, increases in glucocorticoid concentrations from T1 to T2 tended to be associated with higher immune cell deformability, while strongest associations emerged for the increase in cortisone with elevated neutrophil and granulo-monocyte deformability in the 12-month PDD group. Conclusion: Continuously elevated depressive symptomatology as well as an increase in glucocorticoid levels over one year are associated with higher immune cell deformability, particularly in PDD. These findings suggest, that persistent depressive symptomatology associated with increased glucocorticoid secretion may lead to increased immune cell deformability thereby compromising immune cell function and likely contributing to the perpetuation of PDD.

Immune Cell Deformability in Depressive Disorders: Longitudinal Associations Between Depression, Glucocorticoids and Cell Deformability

Neuropsychiatric symptoms (NPS) are important treatment targets in the management of dementia, can be present at very early stages of neurodegeneration, and are associated with more rapid clinical disease progression. Increased cortisol has been reported in Alzheimer’s disease (AD), and has been associated with cognitive decline. At the same time, cortisol is often referred to as the “stress hormone” and elevated cortisol output has been observed in association with depression and delirium. Dehydroepiandrosterone sulfate (DHEAS) has known anti‐glucocorticoid effects and may counter the effects of cortisol.

Clemens Kirschbaum

Papers

Child Neuropsychology: A Journal on Normal and Abnormal Development in Childhood and Adolescence

Automating LC-MS/MS mass chromatogram quantification. Wavelet transform based peak detection and automated estimation of peak boundaries and signal-to-noise ratio using signal processing methods

What to do now that hypocortisol appears to be a predominant sign of long COVID?

Immune Cell Deformability in Depressive Disorders: Longitudinal Associations Between Depression, Glucocorticoids and Cell Deformability

Neuropsychiatric symptoms, Alzheimer’s Disease and Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate: a Prospective Study