Lymph nodes as gatekeepers of autoimmune diseases.

Secondary lymphoid organs such as lymph nodes (LNs) are the home of peripheral tolerance mechanisms which control autoreactive T cells and prevent immune responses to self-antigen. In systemic autoimmunity, there is a clear failure of these peripheral tolerance mechanisms that leads to chronic inflammation and tissue destruction, highlighting the role for LNs as possible gatekeepers of autoimmunity. In recent years there has been a shift in research focus towards tissue sites in autoimmune diseases ranging from type 1 diabetes to rheumatoid arthritis in an effort to better characterise pathogenesis and guide diagnostic and therapeutic decisions.

Characterizing individual trainee learning curves in surgical training: Challenges and opportunities.

The surgical learning curve is an observable and measurable phenomenon. In the era of competency-based approaches to surgical training, monitoring the trajectory of individual trainee competence attainment could represent a meaningful method of formative and summative assessment. While technology can assist this approach, a number of significant barriers to the implementation of such assessment methods remain, including: accurate data collection, standard setting, and reliable assessment.

Defining operative experience targets in surgical training: A systematic review.

Background: The surgical learning curve is an observable and measurable phenomenon. Operative experience targets are well established as a proxy measure for operative competence in surgical training across jurisdictions. The aim of this study was to critique the available evidence regarding the relationship between operative experience in surgical training and trainee competence.

Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes.

Resilient SARS-CoV-2 diagnostics workflows including viral heat inactivation.

There is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not have the capacity to develop these and/or perform manual processing. We provide multiple workflows for SARS-CoV-2 nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek).

Sarcocystis neurona Transmission from Opossums to Marine Mammals in the Pacific Northwest.

Increasing reports of marine mammal deaths have been attributed to the parasite Sarcocystis neurona. Infected opossums, the only known definitive hosts, shed S. neurona sporocysts in their feces.

Harnessing artificial intelligence in cardiac rehabilitation, a systematic review.

This systematic review aims to evaluate the current body of research surrounding the efficacy of artificial intelligence (AI) in cardiac rehabilitation. Presently, AI can be incorporated into personal devices such as smart watches and smartphones, in diagnostic and home monitoring devices, as well as in certain inpatient care settings. The PRISMA guidelines were followed in this review.

Resilient SARS-CoV-2 diagnostics workflows including viral heat inactivation.

There is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not have the capacity to develop these and/or perform manual processing. We provide multiple workflows for SARS-CoV-2 nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek).

Causes of cetacean stranding and death on the Catalonian coast (western Mediterranean Sea), 2012-2019.

The causes of cetacean stranding and death along the Catalan coast between 2012 and 2019 were systematically investigated. Necropsies and detailed pathological investigations were performed on 89 well-preserved stranded cetaceans, including 72 striped dolphins Stenella coeruleoalba, 9 Risso's dolphins Grampus griseus, 5 bottlenose dolphins Tursiops truncatus, 1 common dolphin Delphinus delphis, 1 Cuvier's beaked whale Ziphius cavirostris and 1 fin whale Balaenoptera physalus. The cause of death was determined for 89.

Ingestion of foreign materials by odontocetes along the Catalan coast: causes and consequences.

Ingestion of abnormal materials by cetaceans has been reported worldwide, but few studies have investigated the causes of foreign material ingestion. We retrospectively analysed necropsies performed between 2012 and 2019 on 88 cetaceans stranded along the coast of Catalonia, Spain, and evaluated the association of abnormal ingested materials with 2 risk factors, namely disease of the central nervous system (CNS) and maternal separation. Abnormal materials were found in the digestive tract in 19 of 88 (21.

Inclusion of medical fitness to drive in medical postgraduate training curricula.

Background: Transport mobility and access to driving are important factors in social inclusion and wellbeing. Doctors have an important role to play in supporting safe mobility through applying the knowledge developed in the field of traffic medicine and incorporating state of the art national and international medical fitness to drive (MFTD) guidelines. Little is known about the profile of MFTD in postgraduate curricula for core and higher specialist training.

IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4 T Cells.

The expression of anti-inflammatory IL-10 by CD4 T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-α blockade during T cell stimulation in CD4 T cell/monocyte cocultures resulted in maintenance of IL-10-producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4 T cell-only culture system.

Anti-TNF treatment negatively regulates human CD4 T-cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype.

TNF-blockade has shown clear therapeutic value in rheumatoid arthritis and other immune-mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF-blockade on CD4 T cell activation, maturation, and proliferation, and assessed whether TNF-inhibitors confer regulatory potential to CD4 T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4 T cells with the anti-TNF monoclonal antibody adalimumab promoted IL-10 expression in CD4 T cells, whilst decreasing cellular activation.

Free Functional Muscle Transfer Tendon Insertion Secondary Advancement Procedure to Improve Elbow Flexion.

One method of restoring elbow flexion in patients with brachial plexus injuries is through the use of free functional muscle transfer. Most of our patients achieve good outcome, resulting in improved usefulness of the affected limb. However, a minority of our patients have successful reinnervation of the transferred muscle but with a suboptimal strength and range of motion (ROM) of elbow flexion.

Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin.

Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied.

TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cells.

Background: CD248 is a cell surface glycoprotein, highly expressed by stromal cells and fibroblasts of tumors and inflammatory lesions, but virtually undetectable in healthy adult tissues. CD248 promotes tumorigenesis, while lack of CD248 in mice confers resistance to tumor growth. Mechanisms by which CD248 is downregulated are poorly understood, hindering the development of anti-cancer therapies.

Clinical characteristics and HPV type in recurrent respiratory papillomatosis in Colombia.

Objective: Describe factors associated with aggressive forms of recurrent respiratory papillomatosis (RRP).

Materials And Methods: One hundred eighty-nine RRP cases diagnosed between 1985 and 2009 were identified in pathological records. HPV was detected by the SPF-10 method with broad spectrum primers, (version 1).

Human papillomavirus genotype detection in recurrent respiratory papillomatosis (RRP) in Colombia.

Background: Knowledge on human papillomavirus (HPV) genotype distribution in recurrent respiratory papillomatosis (RRP) is essential to assess the impact of HPV vaccine. It is provided information for Colombia.

Methods: In all, 189 RRP primary cases diagnosed between 1985 and 2009 were identified from 5 pathology laboratories of Cali and Medellin, Colombia.

The thio-adduct facilitated, enzymatic kinetic resolution of 4-hydroxycyclopentenone and 4-hydroxycyclohexenone.

The addition of 3,4-dimethoxybenzyl thiol 8, as a benzyl thiol surrogate, to racemic 4-hydroxycyclopent-2-enone 2 and 4-hydroxycyclohex-2-enone 15 gave the corresponding cis-adducts (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclopentanone 4b and (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclohexanone 16 with good diastereocontrol. In both cases, subsequent treatment with vinyl acetate, in the presence of a lipase enabled enantiomer resolution. Thus, (+)-16 and the acetate of its enantiomer, (-)-(1R,2S)-2-(3,4-dimethoxybenzylthio)-4-oxocyclohexyl acetate, (-)-17 were isolated in 98% enantiomeric excess.

Laboratory diagnosis of Clostridium difficile-associated disease in the Republic of Ireland: a survey of Irish microbiology laboratories.

The Health Protection Surveillance Centre (HPSC) established a group to produce national guidelines for Clostridium difficile in Ireland in 2006. A laboratory questionnaire was distributed to determine current C. difficile diagnostic practices.

Exceptional stereoselectivity in the synthesis of 1,3,4-trisubstituted 4-carboxy beta-lactam derivatives from amino acids.

[reaction: see text] The base-promoted cyclization of optically pure N-(p-methoxybenzyl)-N-(2-chloro)propionyl amino acid derivatives resulted in a diastereo- and enantioselective approach to valuable 1,3,4,4-tetrasubstituted beta-lactams. The stereochemical outcome of the reaction is exclusively governed by the configuration of the N-(2-chloro)propionyl moiety.