TWEAK transactivation of the epidermal growth factor receptor mediates renal inflammation

TWEAK, a member of the TNF superfamily, binds to the Fn14 receptor, eliciting biological responses. EGFR signalling is involved in experimental renal injury. Our aim was to investigate the relationship between TWEAK and EGFR in the kidney. Systemic TWEAK administration into C57BL/6 mice increased renal EGFR phosphorylation, mainly in tubular epithelial cells. In vitro, in these cells TWEAK phosphorylated EGFR via Fn14 binding, ADAM17 activation and subsequent release of the EGFR ligands HB‐EGF and TGFα. In vivo the EGFR kinase inhibitor Erlotinib inhibited TWEAK‐induced renal EGFR activation and downstream signalling, including ERK activation, up‐regulation of proinflammatory factors and inflammatory cell infiltration. Moreover, the ADAM17 inhibitor WTACE‐2 also prevented those TWEAK‐induced renal effects. In vitro TWEAK induction of proinflammatory factors was prevented by EGFR, ERK or ADAM17 inhibition. In contrast, EGFR transactivation did not modify TWEAK‐mediated NF‐κB activation. Our data suggest that TWEAK transactivates EGFR in the kidney, leading to modulation of downstream effects, including ERK activation and inflammation, and suggest that inhibition of EGFR signalling could be a novel therapeutic tool for renal inflammation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Immunoglobulin G from Breast Cancer Patients Regulates MCF-7 Cells Migration and MMP-9 Activity by Stimulating Muscarinic Acetylcholine Receptors

Purpose

We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in human breast tumors. The activation of these receptors triggered tumor cell proliferation. Considering that invasion and metastasis is the major cause of death in cancer, we investigated the action of autoantibodies against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF-7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Methods

Immunoglobulin G (IgG) was purified by chromatography in protein G-agarose from blood samples of breast cancer patients obtained under informed consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was quantified by zymography.

Results

T1N0Mx-IgG promoted tumor cell migration and increased MMP9 activity mimicking the action of the muscarinic agonist carbachol. This effect was reduced not only by the presence of atropine but also by 4-DAMP or tropicamide, antagonists for M₃ and M₄ mAChR subtypes respectively. The actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Conclusions

IgG from breast cancer patients in stage I could be promoting tumor progression by regulating migration and MMP-9 activity in tumor cells via mAChR activation. The presence of these autoantibodies could be determining the prognosis of breast cancer in these patients.     

Construction of an intercultural preventive strategy of alcohol use in rural Mapuche communities: A community‐based participatory research

The research presented in this paper consists of a case study that analyses the elements necessary for a culturally grounded methodological strategy for the prevention of problematic alcohol consumption in rural Mapuche communities in the Araucanía region. To do this, we proposed to answer the questions: what are the particularities that alcohol consumption adopts in the local space? And what are the elements that should be considered for an intercultural preventive strategy for alcohol consumption? Oriented to the perspective of community‐based participatory research, data were collected through group interviews with the local community, participant observation and in‐depth interviews with people who consumed alcohol, were recovering from consumption and nondrinkers. A total of 84 people participated and the information gathered was analysed using ATLAS.ti software. The results show key aspects that must be considered for the design, including: strengthening the cultural identity, providing spaces for shared reflection in places where the community converges (schools and rural health centres), and problematising alcohol consumption from their own conceptions of normal and problematic consumption. Therefore, there is a need to focus on strengthening intracultural processes in community spaces, with a preventive strategy within the logic of action research, with increasing degrees of community participation.     

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.     

Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019).Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed.In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients.Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.     

Recommendations for Managing Endodontic Emergencies during Coronavirus Disease 2019 Outbreak

IntroductionThe management of endodontic emergencies has been particularly challenging during the coronavirus disease 2019 (COVID-19) outbreak because of the possible generation of airborne particles and aerosols. The aim of this report was to contribute to the practice of endodontics by proposing a general protocol for the management of emergencies showing the rationale for remote diagnosis, clinical procedures, and the use of personal protective equipment and barriers at the dental office during the COVID-19 outbreak.MethodsA review of the literature was conducted up to May 2020 on relevant institutional sites, aiming to retrieve the best updated evidence. The reporting considered the Reporting Tool for Practice Guidelines in Health Care statement.ResultsRecommendations from Cochrane Oral Health, the American Dental Association, and the Centers for Disease Control and Prevention were included along with the American Association of Endodontists resources and scientific articles that addressed the issue.ConclusionsThe proposed protocol could contribute to the management of endodontic emergencies at the dental office during the COVID-19 outbreak.     

Measurement of transmission of vibration through the human spine using skin-mounted inertial sensors

The purpose of this study was to examine the feasibility of measuring the transmission of vibration using skin mounted inertial sensors and to assess the dynamic properties of the human spine during activities of daily living. Two inertial sensors were attached to skin overlying the first thoracic vertebra (T1) and another one over the first sacral vertebra (S1) with double sided adhesive tape. Subjects walked along a straight line, and up and down stairs at a self selected, comfortable speed. Transmissibility of vertical vibration was calculated as the ratio of the power spectral density of the acceleration signal at T1 over that at S1, over the frequency range of 0.5–12 Hz. Cross correlation and coherence of the acceleration signals between the two T1 sensors were performed to evaluate the similarity of the data after correction. Cross correlation of signals between trials was also performed to examine the repeatability of the signals. Cross correlation coefficients were found to be very high (>0.9). Inter-trial consistency of the signals of all sensors was also high (>0.9). It is concluded that skin measurement of transmission of vertical vibration is feasible with the inertial sensors and correction method presented. Different physical activities seem to elicit different frequency characteristics of vibration.