Mauro Colombo Golgi Cenci Foundation, Milan, Italy Correspondence: Mauro Colombo, Email email protected View the original paper by Dr Azhar and colleagues
Basophils, eosinophils and mast cells were first recognized by Paul Ehrlich in the late 19th century. These cells have common, but non-redundant roles, in the pathogenesis of allergic diseases and in ...the protection against parasites. Nevertheless, in virtue of their shared-adeptness to produce a huge variety of immunological mediators and express membrane-bound receptors, they are able to interact with immune and non-immune components of the tissue microenvironment, contributing to the regulation of tissue homeostasis and immune response while participating to further deregulation of tissues transforming into neoplasia.
The aim of this study was to assess the mean of histamine concentration in food poisoning.
Systematic review and meta-analysis of reports published between 1959 and 2013.
Main criteria for inclusion ...of studies were: all report types that present outbreaks of "histamine poisoning' or "scombroid syndrome" from food, including histamine content and type of food. Health status of people involved must be nonpathological.
Fifty-five (55) reports were included, these studies reported 103 incidents. All pooled analyses were based on random effect model; histamine mean concentration in poisoning samples was 1107.21 mg/kg with confidence interval for the meta-mean of 422.62-2900.78 mg/kg; heterogeneity index (I2) was 100% (P < 0.0001); prediction interval was 24.12-50822.78 mg/kg. Fish involved in histamine poisoning was mainly tuna or Istiophoridae species. No clues of association between concomitant conditions (female sex, alcohol consumption, previous medication, and consumption of histamine releasing food) and histamine poisoning, were highlighted.
This is the first systematic review and meta-analysis that analyzes all the available data on histamine poisoning outbreaks evaluating the histamine concentration in food involved. Histamine mean concentration in poisoning samples was fairly high. Our study suffers from some limitations, which are intrinsic of the studies included, for instance the lack of a complete anamnesis of each poisoning episode. Protocol registration: Methods were specified in advance and have been published as a protocol in PROSPERO database (18/07/2012 -CRD42012002566).
We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence ...different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota.
Abstract Introduction The gold standard for restoring bone defects is still considered to be autologous bone grafting. However, clinical benefits are not guaranteed and donor-site complications and ...morbidity is not infrequent. Research is on-going for the development of alternative bone substitutes of both biological and synthetic origin. The purpose of this study was to evaluate the type of materials used and their efficacy for the treatment of large bone defects in traumatology and orthopaedic surgery. Materials and method A literature review was carried out of Embase and PubMed databases. Inclusion criteria were articles in English language focusing on the use of bone substitutes in trauma and orthopaedic surgery for the treatment of bone defects and included details on the structural, biological or biomechanical properties of the pure product. Furthermore, based on two clinical challenges, fracture non-union and impaction grafting we elaborated on the use of polytherapy for large bone defects as guided by the diamond concept. Results All the products indicated in this manuscript possess osteoconductive activities but have different resorption times and biomechanical properties. Bone graft substitute materials are used for a wide range of clinical applications even when the level of clinical evidence is low. The size and location of the defect and the local biological and mechanical environment as well as the biomechanical characteristics of the material determine the type of device that can be implanted in a bone defect. Conclusion Proper assessment of the biological and mechanical environment and accurate patient selection are necessary to judge the extent of therapy the injury warrants. A sound understanding of various aspects of biomaterial properties and their relation and influence towards bone healing is of utmost importance. We suggest the application of polytherapy for the treatment of large bone defects and advocate the use of the diamond concept as a guideline.
•Currently, only patients with PD-L1 TPS ≥ 50% can receive immunotherapy (pembrolizumab) as first line treatment in clinical practice and they account for a maximum of 30% of all advanced NSCLC ...patients.•Several phase III studies demonstrated a survival advantage combining immunotherapy to chemotherapy.•An open issue is how to choose the most correct therapeutic strategy and to properly select patients for the different available treatment options.•To date, PD-L1 expression by immunohistochemistry (IHC) is the only approved marker to select patients for immunotherapy but other factors, for example TMB, are under evaluation.
Immunotherapy has dramatically changed the therapeutic scenario in treatment naïve advanced non-small cell lung cancer (NSCLC). While single agent pembrolizumab has become the standard therapy in patients with PD-L1 expression on tumor cells ≥ 50%, the combination of pembrolizumab or atezolizumab and platinum-based chemotherapy has emerged as an effective first line treatment regardless of PD-L1 expression both in squamous and non-squamous NSCLC without oncogenic drivers. Furthermore, double immune checkpoint inhibition has shown promising results in treatment naïve patients with high tumor mutational burden (TMB). Of note, the presence of both negative PD-L1 expression and low TMB may identify a subgroup of patients who has little benefit from immunotherapy combinations and for whom the best treatment option may still be platinum-based chemotherapy. To date, first-line single agent immune checkpoint blockade has demonstrated limited activity in EGFR mutated NSCLC and the combination of immunotherapy and targeted agents has raised safety concerns in both EGFR and ALK positive NSCLC patients. Finally, in EGFR mutated or ALK rearranged NSCLC, atezolizumab in combination with platinum-based chemotherapy and bevacizumab is emerging as a potential treatment option upon progression to first line tyrosine kinase inhibitors.
In the majority of cell types, multivesicular bodies (MVBs) are a special kind of late endosomes, crucial intermediates in the internalization of nutrients, ligands and receptors through the ...endolysosomal system. ESCRT-0, I, II and III (endosomal sorting complex required for transport) are involved in the sorting of proteins into MVBs, generating the intraluminal vesicles. Autophagy is a lysosomal degradation pathway for cytoplasmic components such as proteins and organelles. The autophagosome, a well-characterized structure of the autophagy pathway, can fuse with endocytic structures such as MVBs to generate the amphisome. Finally, the amphisome fuses with the lysosome to degrade the material wrapped inside. Currently, clear evidence suggests that efficient autophagic degradation requires functional MVBs. This review highlights the most recent advances in our understanding of the molecular machinery that participates in MVB biogenesis and regulates the interplay between autophagy and this organelle.
Docosahexaenoic acid (DHA) is an essential, omega-3, long-chain polyunsaturated fatty acid that is a key component of cell membranes and plays a vital role in vertebrate brain function. The capacity ...to synthesize DHA is limited in mammals, despite its critical role in neurological development and health. For humans, DHA is most commonly obtained by eating fish. Global warming is predicted to reduce the de novo synthesis of DHA by algae, at the base of aquatic food chains, and which is expected to reduce DHA transferred to fish. We estimated the global quantity of DHA (total and per capita) currently available from commercial (wild caught and aquaculture) and recreational fisheries. The potential decrease in the amount of DHA available from fish for human consumption was modeled using the predicted effect of established global warming scenarios on algal DHA production and ensuing transfer to fish. We conclude that an increase in water temperature could result, depending on the climate scenario and location, in a ~ 10 to 58% loss of globally available DHA by 2100, potentially limiting the availability of this critical nutrient to humans. Inland waters show the greatest potential for climate-warming-induced decreases in DHA available for human consumption. The projected decrease in DHA availability as a result of global warming would disproportionately affect vulnerable populations (e.g., fetuses, infants), especially in inland Africa (due to low reported per capita DHA availability). We estimated, in the worst-case scenario, that DHA availability could decline to levels where 96% of the global population may not have access to sufficient DHA.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been and is still widely used as an adjuvant in clinical trials of vaccination with autologous tumor cells, peptides and/or dendritic ...cells in a variety of human neoplasms. This cytokine was administered either as product of gene-transduced tumor cells or as recombinant protein together with the vaccine given subcutaneously or intradermally. Results of these trials were heterogeneous in terms of induction of vaccine-specific immune response and of clinical response. Though in some of these studies GM-CSF appeared to help in generating an immune response, in others no effect or even a suppressive effect was reported. Here, we review the literature dealing with the immune adjuvant activity of GM-CSF both in animal models and clinical trials. As a consequence of such analysis, we conclude that GM-CSF may increase the vaccine-induced immune response when administered repeatedly at relatively low doses (range 40–80 μg for 1–5 days) whereas an opposite effect was often reported at dosages of 100–500 μg. The potential mechanisms of the GM-CSF-mediated immune suppression are discussed at the light of studies describing the activation and expansion of myeloid suppressor cells by endogenous tumor-derived or exogenous GM-CSF.
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