Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β‐cells, and to recognise and revert the physiopathology of ...diabetes. Indeed, integrin‐mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β‐cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin‐mediated cell‐matrix adhesions and how they are affected during diabetes. To treat diabetes, a promising approach consists in replacing β‐cells by transplantation. However, efficiency is low, because β‐cells suffer of anoikis, due to enzymatic digestion of the pancreatic ECM, which affects the survival of insulin‐secreting β‐cells. The strategy of adding ECM components during transplantation, to reproduce the pancreatic microenvironment, is a challenging task, as many of the regulatory mechanisms that control ECM deposition and turnover are not sufficiently understood. A better comprehension of the impact of the ECM on the adhesion and integrin‐dependent signalling in β‐cells is primordial to improve the healthy state of islets to prevent the onset of diabetes as well as for enhancing the efficiency of the islet transplantation therapy.
Review: Proper pancreatic ß‐cell function requires ECM adhesion that is altered in diabetes. In response to glucose stimulation, actin remodelling and integrin‐mediated adhesion signalling regulate insulin release. The preservation of the pancreatic and islet ECM is primordial to maintain ß‐cell function. In contrast, diabetic conditions activate pancreatic stellate cells (PSC) that alter ECM composition and deposition, which in turn modify integrin‐mediated adhesion signalling, leading to an insulin secretion‐defect and ß‐cell death.
Cell Adhesion by Integrins Bachmann, Michael; Kukkurainen, Sampo; Hytönen, Vesa P ...
Physiological reviews,
10/2019, Volume:
99, Issue:
4
Journal Article
Peer reviewed
Open access
Integrins are heterodimeric cell surface receptors ensuring the mechanical connection between cells and the extracellular matrix. In addition to the anchorage of cells to the extracellular matrix, ...these receptors have critical functions in intracellular signaling, but are also taking center stage in many physiological and pathological conditions. In this review, we provide some historical, structural, and physiological notes so that the diverse functions of these receptors can be appreciated and put into the context of the emerging field of mechanobiology. We propose that the exciting journey of the exploration of these receptors will continue for at least another new generation of researchers.
Minimalist shoes (MS) are beneficial for foot health. The foot is a part of the posterior chain. It is suggested that interventions on the plantar foot sole also affect the upper segments of the ...body. This study aimed to investigate the local and remote effects along the posterior chain of four weeks of MS walking in recreationally active young adults. 28 healthy participants (15 female, 13 male; 25.3 ± 5.3 years; 70.2 ± 11.9 kg; 175.0 ± 7.8 cm) were randomly assigned to a control- or intervention group. The intervention group undertook a four-week incremental MS walking program, which included 3,000 steps/day in the first week, increasing to 5,000 steps/day for the remaining three weeks. The control group walked in their preferred shoe (no MS). We assessed the following parameters in a laboratory at baseline M1, after the four-week intervention M2, and after a four-week wash-out period M3: Foot parameters (i.e., Foot Posture Index-6, Arch Rigidity Index), static single-leg stance balance, foot-, ankle-, and posterior chain range of motion, and muscle strength of the posterior chain. We fitted multiple hierarchically built mixed models to the data. In the MS group, the Foot Posture Index (b = -3.72, t(51) = -6.05, p .05). The improvements remained at M3 (Foot Posture Index: b = -1.71, t(51) = -2.73, p = .009, -4,94,0.48; balance: b = -15.97, t(49) = -2.25, p = .03, -29.72, 2.21). Walking in MS for four weeks might be advantageous for foot health of recreationally active young adults but no chronic remote effects should be expected.
Summary
From the onset of melanocyte specification from the neural crest, throughout their migration during embryogenesis and until they reside in their niche in the basal keratinocyte layer, ...melanocytes interact in dynamic ways with the extracellular environment of the growing embryo. To recognize and to adhere to their environment, melanocytes depend on heterodimeric cell surface receptors of the family of integrins. In addition to the control of adhesive interactions between melanocytes and the extracellular matrix scaffold secreted by fibroblasts and keratinocytes, the integrin receptors allow cells also to sense the mechanical condition of the extracellular environment, responding by intracellular signaling, triggering cell survival, proliferation or migration events. In this review, we summarize the recently emerged concepts that explain integrin‐dependent adhesion and how this adhesion system interfaces with integrin‐dependent signaling events. The gained information will help to understand melanocyte behavior in pathological situations such as melanoma growth and metastasis formation.
Adenoma detection is a highly personalized task that differs markedly among endoscopists. Technical advances are therefore desirable for the improvement of the adenoma detection rate (ADR). An ...automated computer-driven technology would offer the chance to objectively assess the presence of colorectal polyps during colonoscopy. We present here the application of a real-time automated polyp detection software (APDS) under routine colonoscopy conditions.
This was a prospective study at a university hospital in Germany. A prototype of a novel APDS (“KoloPol,” Fraunhofer IIS, Erlangen, Germany) was used for automated image-based polyp detection. The software functions by highlighting structures of possible polyp lesions in a color-coded manner during real-time colonoscopy procedures. Testing the feasibility of APDS deployment under real-time conditions was the primary goal of the study. APDS polyp detection rates (PDRs) were defined as secondary endpoints provided that endoscopists’ detection served as criterion standard.
The APDS was applied in 55 routine colonoscopies without the occurrence of any clinically relevant adverse events. Endoscopists’ PDRs and ADRs were 56.4% and 30.9%, respectively. The PDRs and ADRs of the APDS were 50.9% and 29.1%, respectively. The APDS detected 55 of 73 polyps (75.3%). Smaller polyp size and flat polyp morphology were correlated with insufficient polyp detection by the APDS.
Computer-assisted automated low-delay polyp detection is feasible during real-time colonoscopy. Efforts should be undertaken to improve the APDS with respect to smaller and flat shaped polyps. (Clinical trial registration number: NCT02838888.)
Display omitted
Abstract Background Transcatheter aortic valve implantation (TAVI) is increasingly applied for aortic stenosis in elderly patients with impaired mobility and reduced quality of life. These patients ...may particularly benefit from post-interventional exercise programs, but no randomized study has evaluated the safety and efficacy of exercise in this population. Methods In a prospective pilot study, 30 patients after TAVI (mean age 81 ± 6 yrs., 44% female, 83 ± 34 days post-intervention) were randomly allocated 1:1 to eight weeks of supervised combined endurance and resistance training (TG) or to usual care (UC). The formal primary efficacy endpoint was between-group difference in change in peak oxygen uptake (VO2 peak) assessed by cardiopulmonary exercise testing; secondary endpoints included muscular strength, 6-min walk distance, and quality of life (KCCQ and SF12 questionnaires). Safety was assessed by documenting training-related adverse events, prosthesis and renal function. Results Significant changes in favor of TG were observed for VO2 peak (group difference 3.7 ml/min/kg (95%-CI 1.1–6.3, P = .007)), muscular strength (bench press 6 kg (3–10, P = .002), rowing 7(3–11, P < .001), pulldown 9(4–14, P = .001), shoulder press 5(1–8, P = .008), leg press 17(6–28, P = .005)), components of quality of life (KCCQ physical limitation 19.2(4.1–34.2, P = .015), symptom burden 12.3(0.5–24.0, P = .041), clinical summary 12.4(3.4–21.4, P = .009)), but not for other questionnaire subscales and 6-min walk distance (15 m (−23–53, P = .428)). Three dropouts unrelated to exercise occurred (TG = 2, UC = 1); prosthesis and renal function were not affected by the exercise intervention. Conclusions In patients after TAVI, exercise training appears safe and highly effective with respect to improvements in exercise capacity, muscular strength and quality of life. Clinical Trial Registration: Clinicaltrials.gov NCT01935297
Acute type B aortic dissections (TBADs) can have immediate or delayed complications within the first 2 weeks. Because the majority of clinical series retrospectively categorized TBAD, the incidence ...and outcome of delayed complications in initially uncomplicated TBAD within the first 14 days are not well described.
We retrospectively analyzed 86 patients (78% male; age, 62.5 ± 13 years) with acute TBAD treated consecutively between January 2004 and May 2016 at a tertiary referral center. All TBADs were confirmed by computed tomography angiography (CTA) on admission, after 2 to 5 days, and after 10 to 14 days. Study end points were the incidence of immediate and delayed complications (aortic rupture, malperfusion, rapid aortic expansion >4 mm, pain or hypertension resistant to medical therapy) and in-hospital mortality. In addition, we looked at CTA-detected morphometric variables (maximum diameters of descending aorta, false lumen FL, and primary entry tear; number of intimal tears; FL configuration; true lumen collapse; course of the dissection) and their association with delayed complications. Finally, we assessed treatment modalities and clinical outcomes.
Of all TBADs, 22 (26%) presented with immediate complications (rupture, n = 11); 64 patients (74%) were initially assessed as having uncomplicated TBAD. Of these 64 patients, 24 (28% of all 86) suffered from delayed complications (malperfusion, n = 10; aortic rupture, n = 3; early expansion >4 mm, n = 8; refractory pain, n = 2; uncontrollable hypertension, n = 1) at a median interval of 7.1 (2-14) days after symptom onset. During the first 14 days, 40 patients (46%) remained uncomplicated. The CTA analysis revealed a significant association of initial thoracic aortic diameter (P = .009), size of the primary entry tear (P = .018), true lumen collapse (P = .019), and partially thrombosed FL (P = .019) with the occurrence of delayed complications within the first 14 days. Of the patients with delayed complications, 87.5% underwent surgery (90% thoracic endovascular aortic repair, 10% peripheral revascularization); 12.5% in this group died following aortic rupture before they received surgical repair. The mortality of patients with delayed complicated TBAD was significantly higher compared with those who remained uncomplicated within the 14-day period (12.5% vs 0%; P = .0221).
Delayed complications in initially uncomplicated acute TBAD are not infrequent. Morphologic variables like maximum diameter of the descending aorta, primary entry tear, true lumen collapse, and partially thrombosed FL were associated with an increased risk of delayed complications in initially uncomplicated TBAD. Future clinical research must verify the predictive role of clinical and morphologic variables in the acute phase, particularly with regard to a possible early surgical treatment to prevent a fatal outcome.
Subcortical stimulation is a method used to evaluate the distance from the stimulation site to the corticospinal tract (CST) and to decide whether the resection of an adjacent lesion should be ...terminated to prevent damage to the CST. However, the correlation between stimulation intensity and distance to the CST has not yet been clearly assessed. The objective of this study was to investigate the appropriate correlation between the subcortical stimulation pattern and the distance to the CST.
Monopolar subcortical motor evoked potential (MEP) mapping was performed in addition to continuous MEP monitoring in 37 consecutive patients with lesions located in motor-eloquent locations. The proximity of the resection cavity to the CST was identified by subcortical MEP mapping. At the end of resection, the point at which an MEP response was still measurable with minimal subcortical MEP intensity was marked with a titanium clip. At this location, different stimulation paradigms were executed with cathodal or anodal stimulation at 0.3-, 0.5-, and 0.7-msec pulse durations. Postoperatively, the distance between the CST as defined by postoperative diffusion tensor imaging fiber tracking and the titanium clip was measured. The correlation between this distance and the subcortical MEP electrical charge was calculated.
Subcortical MEP mapping was successful in all patients. There were no new permanent motor deficits. Transient new postoperative motor deficits were observed in 14% (5/36) of cases. Gross-total resection was achieved in 75% (27/36) and subtotal resection (> 80% of tumor mass) in 25% (9/36) of cases. Stimulation intensity with various pulse durations as well as current intensity was plotted against the measured distance between the CST and the titanium clip on postoperative MRI using diffusion-weighted imaging fiberitracking tractography. Correlational and regression analyses showed a nonlinear correlation between stimulation intensity and the distance to the CST. Cathodal stimulation appeared better suited for subcortical stimulation.
Subcortical MEP mapping is an excellent intraoperative method to determine the distance to the CST during resection of motor-eloquent lesions and is highly capable of further reducing the risk of a new neurological deficit.
Anti-viral immunity continuously declines over time after SARS-CoV-2 infection. Here, we characterize the dynamics of anti-viral immunity during long-term follow-up and after BNT162b2 ...mRNA-vaccination in convalescents after asymptomatic or mild SARS-CoV-2 infection. Virus-specific and virus-neutralizing antibody titers rapidly declined in convalescents over 9 months after infection, whereas virus-specific cytokine-producing polyfunctional T cells persisted, among which IL-2-producing T cells correlated with virus-neutralizing antibody titers. Among convalescents, 5% of individuals failed to mount long-lasting immunity after infection and showed a delayed response to vaccination compared to 1% of naïve vaccinees, but successfully responded to prime/boost vaccination. During the follow-up period, 8% of convalescents showed a selective increase in virus-neutralizing antibody titers without accompanying increased frequencies of circulating SARS-CoV-2-specific T cells. The same convalescents, however, responded to vaccination with simultaneous increase in antibody and T cell immunity revealing the strength of mRNA-vaccination to increase virus-specific immunity in convalescents.
Monocytes are key players in atherosclerotic. Human monocytes display a considerable heterogeneity and at least three subsets can be distinguished. While the role of monocyte subset heterogeneity has ...already been well investigated in coronary artery disease (CAD), the knowledge about monocytes and their heterogeneity in peripheral artery occlusive disease (PAOD) still is limited. Therefore, we aimed to investigate monocyte subset heterogeneity in patients with PAOD. Peripheral blood was obtained from 143 patients suffering from PAOD (Rutherford stage I to VI) and three monocyte subsets were identified by flow cytometry: CD14
CD16
classical monocytes, CD14
CD16
non-classical monocytes and CD14
CD16
intermediate monocytes. Additionally the expression of distinct surface markers (CD106, CD162 and myeloperoxidase MPO) was analyzed. Proportions of CD14
CD16
intermediate monocyte levels were significantly increased in advanced stages of PAOD, while classical and non-classical monocytes displayed no such trend. Moreover, CD162 and MPO expression increased significantly in intermediate monocyte subsets in advanced disease stages. Likewise, increased CD162 and MPO expression was noted in CD14
CD16
classical monocytes. These data suggest substantial dynamics in monocyte subset distributions and phenotypes in different stages of PAOD, which can either serve as biomarkers or as potential therapeutic targets to decrease the inflammatory burden in advanced stages of atherosclerosis.
PDF
