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

https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

/pdf/how-do-glucocorticoids-influence-stress-responses-4egr3fa2k0.pdf

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.

/pdf/receiver-operating-characteristic-roc-plots-a-fundamental-1bsmhsp7j4.pdf

Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.

Molecular mechanisms of epithelial–mesenchymal transition

At laparoscopy performed in the early luteal phase the presence of a corpus luteum with or without ovulation stigma was evaluated in 24 women. At the same time the progesterone concentration in peritoneal fluid and serum was determined. Women (20/24) without ovulation stigma and with low peritoneal progesterone concentration, were considered to have a luteinized unruptured follicle syndrome (LUF syndrome). In 24 women an ambulatory puncture of the pouch of Douglas was performed at the same time in the next cycle. Almost all women (19/ 20) without ovulation stigma and low peritoneal fluid progesterone concentration, again showed a low progesterone concentration in peritoneal fluid, suggesting the continuancy of the LUF syndrome. Fifteen patients were stimulated with human menopausal gonadotropins (hMG), twelve of which also received human chorionic gonadotropins (hCG). In the latter group eleven had a high peritoneal progesterone concentration as established by another ambulatory puncture. One remained low, as did those (3/15) in whom hCG was withheld due to the occurrence of an endogenous LH peak.

Repetitivity and therapy of luteinized unruptured follicle syndrome

Depuis 1989, les donnees des activites de procreation medicalement assistee (PMA) en Belgique ont ete enregistrees par l’a.s.b.l. BELRAP (Belgian Register for Assisted Procreation). En 1999, fut instaure le “ College des Medecins Specialises en Medecine Reproductive ” qui recut pour mission d’effectuer le controle de qualite et l’enregistrement des donnees de la PMA dans notre pays. En 2001, fut inaugure un systeme d’enregistrement “ on line ” de tous les cycles de traitement, tandis que la structure de la base de donnees correspondante subissait au fil des annees, de nombreuses modifications. Bien que le nombre des cycles de PMA dans notre pays ait considerablement augmente au cours de la derniere decennie et ce principalement en raison de l’introduction de nouvelles techniques telles que l’injection intracytoplasmique d’un spermatozoide (ICSI), les taux de succes par essai sont demeures globalement inchanges, se situant aux alentours de 18,8 % de grossesses evolutives par cycle de traitement entame. La modification la plus importante survenue au cours de la periode analysee est la reduction du nombre d’embryons replaces, passant d’abord de trois a deux, pour evoluer recemment vers la reinsertion d’un seul embryon. Les grossesses multiples sont en effet la complication la plus importante de la PMA et les centres belges ont ete les initiateurs d’une reduction drastique du nombre d’embryons replaces visant a l’eviter. Cette annee, ont ete edictees des dispositions legales qui fixent, d’une part, le nombre d’embryons reinseres en fonction de l’âge de la patiente et du rang de l’essai et reglent, d’autre part, le probleme du remboursement de la PMA dans notre pays, attendu depuis longtemps.

https://www.amub.be/revue-medicale-bruxelles/download/65

Une décennie d'enregistrement des données de la procréation médicalement assistée en Belgique Ten years follow-up of medically assisted procreation in Belgium


 Intracytoplasmic sperm injection (ICSI), developed 30 years ago in our Center, allowed men with low to extremely low sperm quality to become the genetic father of their child. Overall, ICSI is now applied in up to 70% of all ART cycles and has resulted in the birth of millions of children worldwide.
 ICSI circumvents natural sperm selection mechanisms and concerns related to transgenerational inheritance of male infertility following ICSI could not be fully answered till today, given the young age of the offspring born after ICSI. Since genetic abnormalities account for one third of all cases of male factor infertility, it is essential to identify these genetic abnormalities because of the potential risk of their transmission to the offspring through the use of ART. As ICSI is nowadays performed even in couples with normal semen parameters, the disentanglement of procedure-related and parental background-related factors on the health of the offspring is important.
 Due to the safety concerns regarding the health of children born after ART, a longitudinal follow-up program was set up in our Center in the 80’s, resulting in data of more than 50 000 pregnancies. To date, more than 25 000 children are conceived after ICSI in our Center. We have not only the worldwide eldest cohort of ICSI offspring but also a uniform cohort of children and young adults conceived by ICSI because of (severe) male factor infertility.
 We present the results of these prospective studies with focus on the reproductive health in ICSI children between 8 and 22 years and compare these with available data from others. First of all, we will show data on the gonadal function assessed both clinically and by means of biomarkers at pre-pubertal and pubertal ages in ICSI boys. Secondly, we will present findings on the reproductive status of young adult men and women conceived after ICSI between 1992 and 1996: results of hormonal work-up, physical examination and semen parameters for ICSI men and results of hormone levels and antral follicle counts for ICSI women.
 Finally, we will discuss the findings in these cohorts of children and young adults conceived because of male infertility in view of the available literature regarding reproductive function in offspring conceived following ICSI.

O-046 Reproductive prospects for ICSI children

Infertility, a failure of conception after at least 12 months of unprotected intercourse, will affect 14–17% of couples at some time in their reproductive lives. The types of infertility, with their respective frequencies, are tubal and pelvic pathology (35%), male problems (35%), anovulation (15%), unexplained infertility (10%) and other infrequent problems (5%). While anovulation, mild/moderate endometriosis, unexplained infertility and moderate oligozoospermia can be treated with mild ovarian stimulation and timed intercourse and/or intrauterine insemination (IUI), no treatment options are available for nonoperable tubal problems or treatment failures with IUI.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0962279901000242

Intracytoplasmic sperm injection – an update

About 15% of the couples are infertile and need medical assistance for reproduction. In about half of those 15% the infertility is caused by a female pathology. In the female, several causes, alone or in association can be present: blocked Fallopian tubes, anovulation, endometriosis, immunological problems and primary ovarian failure. In some patients no apparent cause for the infertility can be detected, they have so-called unexplained or idiopathic infertility.

A. Van Steirteghem

Papers

Repetitivity and therapy of luteinized unruptured follicle syndrome

Une décennie d'enregistrement des données de la procréation médicalement assistée en Belgique Ten years follow-up of medically assisted procreation in Belgium

O-046 Reproductive prospects for ICSI children

Intracytoplasmic sperm injection – an update

Clinical Aspects of Female Infertility