Leukocyte migration through interstitial tissues is essential for mounting a successful immune response. Interstitial motility is governed by a vast array of cell-intrinsic and cell-extrinsic factors ...that together ensure the proper positioning of immune cells in the context of specific microenvironments. Recent advances in imaging modalities, in particular intravital confocal and multi-photon microscopy, have helped to expand our understanding of the cellular and molecular mechanisms that underlie leukocyte navigation in the extravascular space. In this Review, we discuss the key factors that regulate leukocyte motility within three-dimensional environments, with a focus on neutrophils and T cells in non-lymphoid organs.
Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not ...the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.
The CNS is an immune-privileged environment, yet the local control of multiple pathogens is dependent on the ability of immune cells to access and operate within this site. However, inflammation of ...the distinct anatomical sites (i.e., meninges, cerebrospinal fluid, and parenchyma) associated with the CNS can also be deleterious. Therefore, control of lymphocyte entry and migration within the brain is vital to regulate protective and pathological responses. In this review, several recent advances are highlighted that provide new insights into the processes that regulate leukocyte access to, and movement within, the brain.
The dynamic anatomy and patterning of skin Wong, Richard; Geyer, Stefan; Weninger, Wolfgang ...
Experimental dermatology,
February 2016, Volume:
25, Issue:
2
Journal Article
Peer reviewed
Open access
The skin is often viewed as a static barrier that protects the body from the outside world. Emphasis on studying the skin's architecture and biomechanics in the context of restoring skin movement and ...function is often ignored. It is fundamentally important that if skin is to be modelled or developed, we do not only focus on the biology of skin but also aim to understand its mechanical properties and structure in living dynamic tissue. In this review, we describe the architecture of skin and patterning seen in skin as viewed from a surgical perspective and highlight aspects of the microanatomy that have never fully been realized and provide evidence or concepts that support the importance of studying living skin's dynamic behaviour. We highlight how the structure of the skin has evolved to allow the body dynamic form and function, and how injury, disease or ageing results in a dramatic changes to the microarchitecture and changes physical characteristics of skin. Therefore, appreciating the dynamic microanatomy of skin from the deep fascia through to the skin surface is vitally important from a dermatological and surgical perspective. This focus provides an alternative perspective and approach to addressing skin pathologies and skin ageing.
Connective or muscular tissue crossing the axilla is named axillary arch (of Langer). It is known to complicate axillary surgery and to compress nerves and vessels transiting from the axilla to the ...arm. Our study aims at systematically researching the frequency, insertions, tissue composition and dimension of axillary arches in a large cohort of individuals with regard to gender and bilaterality. In addition, it aims at evaluating the ability of axillary arches to cause compression of the axillary neurovascular bundle. Four hundred axillae from 200 unembalmed and previously unharmed cadavers were investigated by careful anatomical dissection. Identified axillary arches were examined for tissue composition and insertion. Length, width and thickness were measured. The relation of the axillary arch and the neurovascular axillary bundle was recorded after passive arm movements. Twenty‐seven axillae of 18 cadavers featured axillary arches. Macroscopically, 15 solely comprised muscular tissue, six connective tissue and six both. Their average length was 79.56 mm, width 7.44 mm and thickness 2.30 mm. One to three distinct insertions were observed. After passive abduction and external rotation of the arm, 17 arches (63%) touched the neurovascular axillary bundle. According to our results, 9% of the Central European population feature an axillary arch. Approximately 50% of it bilaterally. A total of 40.74% of the arches have a thickness of 3 mm or more and 63% bear the potential of touching or compressing the neuromuscular axillary bundle upon arm movement.
Nine percent of the Central European population has an axillary arch. Approximately half of these are bilateral. A total of 40.74% of the arches have a thickness of 3 mm or more, and 63% can touch or compress the neuromuscular axillary bundle during arm movements.
Ultrasound as a diagnostic tool in thoracic outlet syndrome (TOS) is becoming increasingly important. The aim of this study was to investigate the diagnostic value of ultrasound in detecting the ...axillary arch, an ancillary muscle potentially causing TOS. Two hundred upper limbs of 100 fresh, non-frozen, non-embalmed body donors were screened for axillary arches. Sonographic findings were validated by anatomic dissection. Twelve axillary arches were found in 200 upper extremities, corresponding to a prevalence of 8.0% per individual and 6.0% per upper extremity investigated. Ultrasound had low diagnostic performance in identifying axillary arches, with a sensitivity of 66.7% and specificity of 95.7%. There was a tendency to identify more easily arches consisting of purely muscle tissue. Axillary arch thickness, its cross-sectional area and the predominant tissue type were associated with compression of the neurovascular bundle during shoulder elevation. Ultrasound seems to have limited potential to identify axillary arches. However, arches consisting predominantly of muscle tissue may be identified more easily and were associated with compression of neurovascular structures, thus potentially causing symptoms. Further clinical trials are needed to clarify the true value of ultrasound in patients with symptoms of TOS.
We develop an electrical-impedance tomography (EIT) inverse model problem in an infinite-dimensional setting by introducing a nonlinear elliptic PDE as a new EIT forward model. The new model ...completes the standard linear model by taking the transport of ionic charge into account, which was ignored in the standard equation. We propose Bayesian inversion methods to extract electrical properties of inhomogeneities in the main body, which is essential in medicine to screen the interior body and detect tumors or determine body composition. We also prove well-definedness of the posterior measure and well-posedness of the Bayesian inversion for the presented nonlinear model. The new model is able to distinguish between liquid and tissues and the state-of-the-art delayed-rejection adaptive-Metropolis (DRAM) algorithm is capable of analyzing the statistical variability in the measured data in various EIT experimental designs. This leads to design a reliable device with higher resolution images which is crucial in medicine for diagnostic purposes. We first test the validation of the presented nonlinear model and the proposed inverse method using synthetic data on a simple square computational domain with an inclusion. Then we establish the new model and robustness of the proposed inversion method in solving the ill-posed and nonlinear EIT inverse problem by presenting numerical results of the corresponding forward and inverse problems on a real-world application in medicine and healthcare. The results include the extraction of electrical properties of human leg tissues using measurement data.
•The nonlinear Poisson-Boltzmann equation as a new forward model for EIT is presented.•Well-posedness of Bayesian inversion for the new nonlinear model is proved.•A new direct and inverse methodology for the EIT inverse problem is developed.•The methodology is established by applying on a real-world application in medicine.
The extracellular matrix (ECM) is an integral component of all organs and plays a pivotal role in tissue homeostasis and repair. While the ECM was long thought to mostly have passive functions by ...providing physical stability to tissues, detailed characterization of its physical structure and biochemical properties have uncovered an unprecedented broad spectrum of functions. It is now clear that the ECM not only comprises the essential building block of tissues but also actively supports and maintains the dynamic interplay between tissue compartments as well as embedded resident and recruited inflammatory cells in response to pathologic stimuli. On the other hand, certain pathogens such as bacteria and viruses have evolved strategies that exploit ECM structures for infection of cells and tissues, and mutations in ECM proteins can give rise to a variety of genetic conditions. Here, we review the composition, structure and function of the ECM in cutaneous homeostasis, inflammatory skin diseases such as psoriasis and atopic dermatitis as well as infections as a paradigm for understanding its wider role in human health.
Highlights • Neutrophils engage in homotypic and heterptypic communication with other cells. • Signal relay between neutrophils coordinates their swarming in a feed forward manner. • ...Multi-dimensional crosstalks between neutrophils and other cells choreograph recruitment. • Crosstalks allow neutrophils to exert long-lasting impact beyond their short lifespan.
Cases of inflammatory bowel disease (IBD) during treatment with interleukin (IL)-17 antagonists have been reported from trials in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The aim ...of this study was to assess the overall risk for development of IBD due to IL-17 inhibition.
Systematic review and meta-analysis of studies conducted 2010-2018 of treatment with IL-17 antagonists in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. We compared risk of IBD development in anti-IL-17 treated patients compared to placebo treatments. We also computed incident rates of IBD overall. A 'worst case scenario' defining subjects ambiguous for prevalent versus incident cases for the latter was also applied.
Sixty-six studies of 14,390 patients exposed to induction and 19,380 patients exposed to induction and/or maintenance treatment were included. During induction, 11 incident cases of IBD were reported, whereas 33 cases were diagnosed during the entire treatment period. There was no difference in the pooled risk of new-onset IBD during induction studies for both the best-case risk difference (RD) 0.0001 (95% CI: -0.0011, 0.0013) and worst-case scenario RD 0.0008 (95% CI: -0.0005, 0.0022). The risk of IBD was not different from placebo when including data from maintenance and long-term extension studies RD 0.0007 (95% CI: -0.0023, 0.0036) and RD 0.0022 (95% CI: -0.0010, 0.0055), respectively.
The risk for development of IBD in patients treated with IL-17 antagonists is not elevated. Prospective surveillance of patients treated with IL-17 antagonists with symptom and biomarker assessments is warranted to assess for onset of IBD in these patients.
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