BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway

By diversifying antibody biological effector functions, class switch DNA recombination has a central role in the maturation of the antibody response. Here we show that BCR-signalling synergizes with Toll-like receptor (TLR) signalling to induce class switch DNA recombination. BCR-signalling activates the non-canonical NF-κB pathway and enhances the TLR-dependent canonical NF-κB pathway, thereby inducing activation-induced cytidine deaminase (AID), which is critical for class switch DNA recombination. Escherichia coli lipopolysaccharide (LPS) triggers dual TLR4/BCR-signalling and induces hallmarks of BCR-signalling, including CD79a phosphorylation and Ca2+ mobilization, and activates both the NF-κB pathways to induce AID and class switch DNA recombination in a PI(3)K p85α-dependent fashion. CD40-signalling activates the two NF-κB pathways to induce AID and class switch DNA recombination independent of BCR-signalling. Finally, dual BCR/TLR-engaging NP–lipopolysaccharide effectively elicits class-switched NP-specific IgG3 and IgG2b in mice. Thus, by integrating signals of the non-canonical and canonical NF-κB pathways, BCR and TLRs synergize to induce AID and T-cell-independent class switch DNA recombination

In vivo magnetic resonance spectroscopy: basic methodology and clinical applications

The clinical use of in vivo magnetic resonance spectroscopy (MRS) has been limited for a long time, mainly due to its low sensitivity. However, with the advent of clinical MR systems with higher magnetic field strengths such as 3 Tesla, the development of better coils, and the design of optimized radio-frequency pulses, sensitivity has been considerably improved. Therefore, in vivo MRS has become a technique that is routinely used more and more in the clinic. In this review, the basic methodology of in vivo MRS is described—mainly focused on 1H MRS of the brain—with attention to hardware requirements, patient safety, acquisition methods, data post-processing, and quantification. Furthermore, examples of clinical applications of in vivo brain MRS in two interesting fields are described. First, together with a description of the major resonances present in brain MR spectra, several examples are presented of deviations from the normal spectral pattern associated with inborn errors of metabolism. Second, through examples of MR spectra of brain tumors, it is shown that MRS can play an important role in oncology

Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence

Background: Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12and folate status are associated with an increased fracture risk. As vitamin B12and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration. Methods/Design. The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration ( 12 mol/L). One group receives daily a tablet with 500 g vitamin B12and 400 g folic acid and the other group receives a placebo tablet. In both tablets 15 g (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health

Experiência inicial com o uso de adesivo tissular contendo trombina para tratamento do pseudo-aneurisma femoral Treatment of femoral pseudoaneurysm with thrombin tissue adhesive: initial experience

O pseudo-aneurisma (PSA) após cateterização femoral tem sido diagnosticado com regularidade em serviços com grande movimento de intervenções percutâneas, com incidência variando de 0,05 a 6%. PSA femorais pequenos podem ser acompanhados até a resolução espontânea. As opções de tratamento são: compressão guiada por ultra-som, injeção de trombina para trombose do PSA e tratamento cirúrgico. A injeção percutânea de trombina tem a vantagem de ser um procedimento indolor e rápido. Podem ser utilizados trombina isolada ou preparados contendo trombina associada a fibrinogênio e fatores de coagulação. A experiência inicial dos autores de cinco casos tratados com injeção de adesivo tissular contendo trombina mostrou resultado satisfatório em quatro; um caso necessitou tratamento cirúrgico. Não houve sucesso com uso isolado de trombina humana, porém, ocorreu trombose imediata após injeção de preparado de trombina associada a fibrinogênio/fator XIII. Neste artigo, são discutidas as opções de tratamento dos PSA femorais e a técnica do uso de trombina percutânea.<br>Pseudoaneurysms caused by femoral artery catheterization have been regularly diagnosed in medical units with a great number of percutaneous interventions, with a documented incidence between 0.05 and 6%. Small femoral pseudoaneurysms undergo spontaneous resolution. Treatment options are: ultrasound-guided compression, thrombin injection to induce pseudoaneurysm thrombosis and surgical treatment. Percutaneous thrombin injection has the advantage of being a fast and painless procedure. Both isolated thrombin and thrombin preparations with fibrinogen and coagulation factors can be used. The authors' initial experience with five cases treated with thrombin tissue adhesive showed successful results in four; one case required surgery. There was no success with isolated human thrombin, but immediate thrombosis was achieved after injection of thrombin associated to fibrinogen and factor XIII. In this article, the treatment options for femoral pseudoaneurysms and the technique of percutaneous thrombin are discussed

Incidental pulmonary embolism in oncologic patients—a systematic review and meta-analysis

Purpose!#!Incidental pulmonary embolism (IPE) is a common finding on computed tomography (CT). IPE is frequent in oncologic patients undergoing staging CT. The aim of this analysis was to provide the pooled frequency of IPE and frequencies of IPE in different primary tumors.!##!Methods!#!MEDLINE, SCOPUS, and EMBASE databases were screened for studies investigating frequency of IPE in oncologic staging CT up to February 2020. Overall, 12 studies met the inclusion criteria and were included into the present study.!##!Results!#!The pooled analysis yielded a total of 28,626 patients. IPE was identified in 963 patients (3.36%, 95% CI = 3.15; 3.57). The highest frequency was found in prostate cancer (8.59%, 95%CI = 3.74; 13.44), followed by hepatobiliary carcinoma (6.07%, 95%CI = 3.09; 9.05) and pancreatic cancer (5.65%, 95%CI = 3.54; 7.76). The lowest frequencies were identified in tumors of male reproductive organs (0.79%, 95%CI = 0.21; 1.37) and hematological diseases (1.11% 95%CI = 0.74; 1.48).!##!Conclusion!#!The overall frequency of IPE in oncologic patients was 3.36%. There are considerable differences in regard to primary tumors with the highest frequency in prostate cancer and pancreatic and hepatobiliary carcinomas