Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

A case of concomitant pulmonary tuberculosis and mucormycosis in an insulin-dependent diabetic patient

Conditions, where the patient's immune system is compromised are the main risk factor for mucormycosis. Approximately 23% of the world's population is estimated to have a latent Mycobacterium tuberculosis infection and more than 10 million new cases were estimated in 2017. Pulmonary mucormycosis and tuberculosis co-infections are very rare. We present the case of a 56-year-old insulin-dependent diabetic patient with a pulmonary mucormycosis and tuberculosis co-infection. While the patient did not suffer from ketoacidosis, she had poor glycemic control. A chest X-ray and a computed tomography showed nodular and cavitary lesions in both lungs. The patient was diagnosed through a biopsy of the bronchial mucosa and an RT-PCR for M. tuberculosis from bronchoalveolar lavage. The patient was treated with the recommended 4-drug regimen for TB (i.e. isoniazid, rifampin, pyrazinamide, and ethambutol); concurrently, amphotericin B deoxycholate was administered to treat the mucormycosis infection. Thirty days after initial hospital admission the patient underwent a lobectomy on the right lung. The case described here is only the sixth case reported in the literature of concomitant pulmonary tuberculosis and mucormycosis and the third case associated with a TB and mucormycosis co-infection involving an uncontrolled DM patient to survive

High Sensitivity C Reactive Protein in Patients with Rheumatoid Arthritis Treated with Antibodies against IL-6 or Jak Inhibitors: A Clinical and Ultrasonographic Study

Background: We examined whether high-sensitivity CRP (hsCRP) reflected the inflammatory disease status evaluated by clinical and ultrasound (US) parameters in RA patients receiving IL-6 receptor antibodies (anti-IL-6R) or JAK inhibitors (JAKi). Methods: We conducted a cross-sectional study of patients with established RA receiving anti-IL-6R (tocilizumab, sarilumab) or JAKi (tofacitinib, baricitinib). Serum hsCRP and US synovitis in both hands were measured. Associations between hsCRP and clinical inflammatory activity were evaluated using composite activity indices. The association between hsCRP and US synovitis was analyzed. Results: 63 (92% female) patients (42 anti- IL-6R and 21 JAKi) were included, and the median disease duration was 14.4 (0.2–37.5) years. Most patients were in remission or had low levels of disease. Overall hsCRP values were very low, and significantly lower in anti-IL-6R patients (median 0.04 mg/dL vs. 0.16 mg/dL). Anti-IL-6R (82.4%) patients and 48% of JAKi patients had very low hsCRP levels (≤0.1 mg/dL) (p = 0.002). In the anti-IL-6R group, hsCRP did not correlate with the composite activity index or US synovitis. In the JAKi group, hsCRP moderately correlated with US parameters (r = 0.5) but not clinical disease activity, and hsCRP levels were higher in patients with US synovitis (0.02 vs. 0.42 mg/dL) (p = 0.001). Conclusion: In anti-IL-6R RA-treated patients, hsCRP does not reflect the inflammatory disease state, but in those treated with JAKi, hsCRP was associated with US synovitis

Imaging Findings in Patients with Immune Checkpoint Inhibitor-Induced Arthritis

Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited. Methods: We conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and (18)F-FDG PET/CT)] between January 2017 and January 2022. Results: Nineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 (18)F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen. Conclusions: ICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings

Negotiating Boundaries: The Nurse Family Member Caring for Her Own Relative in Palliative Care

This research illuminates the challenges of living well within one's own family as a nurse caring for her own relative who is dying of a cancer-related illness. Developing a deeper awareness of the consequences of this caring work has been the central focus for inquiry in this research. Nursing requires epistemologies that encompass new ways of understanding how we live within our own families and communities and practice as nurses. The theoretical framework that guides this research interprets the French Philosopher Michel Foucault's (1926-1984) critical history of thought as an ethical project for nursing. It uses conceptual tools developed in his later writing and interviews to draw attention to how discursive knowledge and practices constitute subjectivity in relations of truth, power and the self's relation to the self. The first aspect of the analysis, landscapes of care examines the techniques of discourse as relations of power and knowledge that constitute nurse family members as subjects who have relationships with their own families and other health professionals. The second aspect analyses care of the self and others as self work undertaken to form the self as a particular kind of subject and achieve mastery over one's thoughts and actions. Nurses are called to care because they are present within their families with knowledge and expertise that makes a difference to how a dying relative experiences palliative care. Caring discourse positions nurses with responsibilities to their own; responsibilities that require sensitivity in knowing how to negotiate the relational spaces that constitute relationships with other family members and health professionals. Family discourse calls nurse family members to care as daughters, daughters-in-law, wives or mothers within normative understandings about the obligations that families have to care for their ill or dependent members. The discourse of expertise in knowing as a nurse positions nurse family members as interpreters of information for their families and observers who use their inside knowledge of how the health system works to watch over the ill person's clinical care. This expertise, which becomes visible as the exercise of professional authority in practising nursing, challenges the normative frameworks that classify and demarcate professional and lay roles in caring for the dying person. As an exploration of the complex and contradictory subjectivities of the nurse family member, this research illuminates the forms and limits of nursing practice knowledge. It shows how nursing is practised, and the identity of the nurse is created, through intellectual, political and relational work, undertaken on the self in relation to others, as modes of ethical engagement. Within this ethical engagement, nurse family members work to transform the self into discursive subjects, with the knowledge, skills and other capacities that are necessary to honour their commitments and responsibilities for care of another person. The experience of caring for their own relative transforms nurse family members' previously held values about how nurses ought to be with others in their professional work, creating a deeper sense of interest in and concern for the vulnerability of other people in palliative care

Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid arthritis patients receiving IL-6 antagonists or JAK inhibitors

To analyse the accuracy of plasma calprotectin in patients with rheumatoid arthritis (RA) receiving monoclonal antibodies against IL-6 receptors (anti-rIL-6) or JAK inhibitors (JAKis) in detecting ultrasound (US) synovitis and compare it with acute phase reactants [high-sensitivity C-reactive protein (hs-CRP) and ESR].An observational cross-sectional study of RA patients receiving anti-rIL-6 (tocilizumab or sarilumab) or JAKi, (baricitinib or tofacitinib) was made. Plasma calprotectin for the diagnosis of US synovitis [synovial hypertrophy grade (SH)???2 plus power Doppler signal (PD)???1] was analysed using receiver operating characteristic curves (ROCs). The performance of ESR and hs-CRP was also studied. The three ROC curves were compared to determine which had the highest discriminatory power. Associations between plasma calprotectin and US scores were made using correlation analysis.Sixty-three RA patients were included. Mean plasma calprotectin levels were significantly higher in patients with US synovitis than in those without (0.89?±?0.85 vs 0.30?±?0.12 ?g/ml; p?=?0.0003). A moderate correlation between calprotectin and all US scores (HS score Rho?=?0.479; PD score Rho?=?0.492; and global score Rho?=?0.495) was found. The discriminatory capacity of plasma calprotectin showed an AUC of 0.795 (95% CI: 0.687-0.904). The AUC of hs-CRP and ESR was 0.721 and 0.564, respectively. hs-CRP serum levels showed a low positive correlation with the three US scores (Rho?<?0.40). After analysis according to the drugs administered, the correlation disappeared in patients receiving anti-rIL-6.Plasma calprotectin may be a sensitive biomarker of synovial inflammation in RA patients treated with anti-rIL-6 or JAKi.© The Author(s), 2022

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax