Significance of mast cells in spermatogenesis,implantation, pregnancy,and abortion: Cross talk and molecular mechanisms

Both subsets of MCs including MC_TC (tryptase‐positive, chymase‐positive) and MC_T (tryptase‐positive, chymase‐negative) are present in the testis and epididymis. Increased number of MCs, higher levels of MC‐released tryptase in testis and seminal plasma of males with fertility problems, and promoting sperm motility in individuals with oligozoospermia after using MC blockers provide evidence that MCs may play a role in male infertility/subfertility disturbances. MC‐released tryptase and histamine contribute to the fibrosis and may disrupt spermatogenesis. MCs not only influence the process of spermatogenesis but also have effects on the function of other testis‐residing cells. MC‐derived histamine may influence the steroidogenesis of Leydig cells by acting through H1R and H2R receptors. Additionally, the interaction between MC‐released ATP and P2X receptors expressed on the peritubular cells may induce the production of the pro‐inflammatory mediators by peritubular cells. Further investigations showed that MCs may be involved in the pathology of female infertility during implantation, pregnancy, and abortion. In the uterus, MC_T subtype is abundant in myometrium and adjacent basal layer while MC_TC subtype is distributed in all layers. MCs in response to hormones mainly estradiol and progesterone become activated and release a wide range of mediators including histamine, VEGF, proteases, and metalloproteinases (MMPs) that have a role in different stages of pregnancy. An increasing influx of MCs to the cervix during the pregnancy occurs that helps to the physiologic cervical ripening. While MMPs degrade the extracellular matrix (ECM), VEGF modulates neovascularization and histamine influences the embryo implantation. MC‐derived histamine may have a positive effect during implantation due to its participation in tissue remodeling. MC proteases including tryptase and chymase activate the precursors of MMP2 and MMP9 to mediate ECM degradation during the physiologic menstrual cycle. There is a line of evidence that MCs have a role in abortion by releasing TNF‐α.     

Comprehensive meta-analysis of associations between temperament and character traits in Cloninger’s psychobiological theory and mental disorders

ObjectiveTo explore the relationship between temperament and character traits in Cloninger’s psychobiological theory and mental disorders.Methods: A systematic literature search was conducted of five international databases for all articles published in English between January 1990 and April 2019 (PROSPERO-CRD42019133214). Owing to heterogeneity, pooled estimates of correlations for personality disorders and standardized mean differences for case–control studies related to other mental disorders were calculated using the random-effects method.ResultsThe pooled effect sizes obtained from 149 studies showed that high harm avoidance (related to 22/24 diagnostic categories), low self-directedness (21/23), low cooperativeness (17/23), high self-transcendence (14/23), low reward dependence (11/24), high novelty-seeking (10/24), low novelty-seeking (7/24), high persistence (2/23), low persistence (2/23) and high reward dependence (2/24) were related to psychopathology.ConclusionsAll traits provided unique psychobiological tools for differential diagnosis of mental disorders. However, high harm avoidance and low self-directedness played a canonical role in psychopathology. Despite the study limitations, additional studies are warranted to evaluate the differential diagnoses suggested by the present model.     

Maintenance of CD8+ memory T lymphocytes in the spleen but not in the bone marrow is dependent on proliferation

It is current belief that numbers of CD8⁺ memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here, we compare the proliferation of CD8⁺ memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and bone marrow (BM). Fifty percent of CD8⁺ memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8⁺ memory T lymphocytes are maintained by proliferation. The numbers of CD8⁺ memory T lymphocytes in the BM, however, were not affected by cyclophosphamide. This stability was independent of circulating CD8⁺ memory T cells, blocked by FTY720, showing that BM is a privileged site for the maintenance of memory T lymphocytes, as resident cells, resting in terms of proliferation.     

Absence of alphavbeta6 integrin is linked to initiation and progression of periodontal disease

Integrin alphavbeta6 is generally not expressed in adult epithelia but is induced in wound healing, cancer, and certain fibrotic disorders. Despite this generalized absence, we observed that alphavbeta6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of alphavbeta6 integrin was down-regulated in human periodontal disease, a common medical condition causing tooth loss and also contributing to the development of cardiovascular diseases by increasing the total systemic inflammatory burden. Remarkably, integrin beta6 knockout mice developed classic signs of spontaneous, chronic periodontal disease with characteristic inflammation, epithelial down-growth, pocket formation, and bone loss around the teeth. Integrin alphavbeta6 acts as a major activator of transforming growth factor-beta1 (TGF-beta1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-beta1 and alphavbeta6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks alphavbeta6 integrin-mediated activation of TGF-beta1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, alphavbeta6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-beta1.     

Do they teach what they need to? An analysis of the impact of curriculum mapping on the learning objectives taught in a lecture series in surgery

Abstract

Introduction: Curriculum mapping shows concordances and differences between the intended and the taught curriculum. To our knowledge, no previous studies describe the effects that this mapping has on the curriculum. The aim of the present study is to map the content of a lecture series in surgery to the National Catalogue of Learning Objectives in Surgery and analyze the effects this mapping has on the content of the following lecture series.

Methods: All lecturers in the lecture series were directly observed by a minimum of two reviewers and learning objectives and the level of competence were documented. After the lecture series, the results were visualized within the catalog of learning objectives and were sent to the lecturers. In the following lecture series, learning objectives were documented correspondingly.

Results: In the first lecture series, 47% of the learning objectives were taught. After the mapping, the number of learning objectives that were taught increased to 59% (p?<?0.001). The increase was found in all surgical disciplines and in all levels of competences without any changes in the average duration of the lectures.

Conclusions: The presented method for mapping a curriculum effectively increased the number of taught learning objectives without requiring longer lecture durations.     

Longitudinal Tissue Velocity and Deformation Imaging in Inferobasal Left Ventricular Aneurysm

Background: Longitudinal myocardial tissue velocity imaging (TVI) and strain rate imaging (SRI) quantify regional myocardial function. We aimed to measure TVI and SRI indices for inferobasal aneurysmal segments by echocardiography at rest. Method: Sixteen patients with inferobasal left ventricular (LV) aneurysm, LV ejection fraction (EF) ≤50%, and 14 normal coronaries with normal echocardiography (control group) were studied. In SRI, peak systolic strain (ST), strain rate (SR), and pattern of strain curves and in TVI, peak systolic inward motion (Sm) were evaluated all at rest. Ascending curve means systolic expansion and descending means shortening. Results: LVEF was significantly lower in the patient group. Mean ST, SR, and Sm of inferobasal segment showed significant difference between patient and control groups; for ST: 1.45 ± 7.18% versus ?17.64 ± 7.45%, P < 0.0001; SR: ?0.25 ± 0.26 versus ?1.44 ± 0.64 sec^?1, P < 0.0001; and Sm: 3.85 ± 1.26 versus 5.56 ± 1.28 cm/sec, P = 0.006, respectively. All inferobasal aneurysmal segments had ascending curve while normal segments showed a descending curve. In patient group, aneurysmal segments had significantly reduced ST and SR compared to normal segments. Normal functioning segments of patients showed significant reduction of ST and SR compared to normal LV segments in control subjects. The range of SR and ST for inferobasal aneurysmal segments did not overlap with that of the normal segments (?0.60, 0.19 and ?3.00, ?0.80 sec^?1 for SR, and ?8.30, 23.30 and ?35.30, ?10.00% for ST, respectively). Conclusion: SRI indices were significantly reduced in inferobasal aneurysmal segment in comparison with either the same segment in normal subjects or normal functioning segments in the same patients. SR and ST may be superior to Sm in the evaluation of inferobasal aneurysmal segments. (Echocardiography 2010;27:803‐808)     

l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta

Introduction: Diminished bioavailability of nitric oxide is crucial in endothelial dysfunction and the development of atherosclerosis. Several studies have found that l-arginine as a nitric oxide (NO) donor has beneficial effect in prevention of atherosclerosis, but the mechanism is not completely known. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased inducible NOS (iNOS) expressions might be involved in the preventive effects of l-arginine in hypercholesterolemic rabbits. Methods: Seventeen male rabbits were divided randomly in two groups. They received rabbits chow supplemented with 1% cholesterol (group 1, n = 8) and the other group received also l-arginine (3% in drinking water) (group 2, n = 9) for 1 month. Blood samples were obtained before and after the experiment. At the end of experiment, the aortas were harvested. The serum levels of cholesterol and low-density lipoproteins (LDL) were measured. The intima/media thickness (IMT) ratio was measured and the determination of fatty streak formation was done with the aid of light microscopy. eNOS and iNOS expression in aorta were studied with immuohistochemistery. Results: The IMT ratio in first group having fatty streaks was 0.287 ± 0.15. No fatty streak lesion was detected in l-arginine-treated group. The results also indicated that eNOS expression (intensity) in aortas was significantly higher in l-arginine-treated group (group 1: 13.62 ± 2.7 and group 2: 21.77 ± 2.8; p < 0.05), but no significant difference was observed for iNOS expression between the groups. Conclusion: The expression of eNOS plays an important role in the protection of the vessel wall from atherosclerosis. l-Arginine in drinking water has a beneficial effect in the enhancement of eNOS protein expression.