Ahmadgreve0800

Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against P. falciparum (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to P. berghei CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites.

Many clinicians do not know under what exact conditions extracorporeal membrane oxygenation (ECMO) can get the best results. In this study, we explored the optimal indications for ECMO in patients with refractory cardiogenic shock.

From October 2014 to November 2019, 23 patients with refractory cardiogenic shock were treated with ECMO in our hospital, including 11 cases with acute left anterior myocardial infarction, 3 with acute left inferior and right ventricular myocardial infarction, and 9 with fulminant myocarditis. These cases were divided into survivors (n = 10) and nonsurvivors (n = 13), and the clinical data of the 2 groups were compared.

The weaning rate of ECMO was 60.9%. The discharge survival rate was 43.5%. There were significant differences in age, sequential organ failure assessment (SOFA) score, vasoactive-inotropic (VIS) score, lactic acid concentrations, primary disease, and smoking history between survivors and nonsurvivors before ECMO (P < .05). There were significant differences is a better option.Two recent articles both found that cardiovascular disease was the major comorbidity in patients with COVID-19. Inflammation of the cardiovascular system and hypoxemia in patients with COVID-19 are the important causes of cardiovascular system dysfunction. Through detailed analyses of the cardiovascular system, clinicians may identify specific patterns of cardiovascular abnormalities. If such a model can been established, the prognosis of COVID-19 patients with cardiovascular disease may be predicted.

Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs.

A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe.

Five areas of priority need were identified increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite vailable free of charge to the rheumatology community.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of unknown aetiology. The relationship between CNO and familial Mediterranean fever (FMF) is not clearly documented so far. This cross-sectional study aims to evaluate the clinical and laboratory characteristics of a cohort of CNO patients within the context of its relationship with FMF and MEFV gene mutations.

Demographic and clinical data were extracted from electronic medical records of patients with CNO. The MEFV gene analysis was performed for all patients.

A total number of 18 patients with CNO with a median follow-up of 36.50 (13.00-84.00) months were included in the study. Five patients (27.8%) were found to have at least one exon 10 mutations (four with M694V and one with M680I). Four of them (22.2%) had homozygous or compound heterozygous mutations of the MEFV gene. Two patients had a previous diagnosis of FMF and developed CNO while FMF was under control. Patients with MEFV mutations had an earlier onset of CNO, higher acute phase reactants, lower haemoglobin concentrations, and a higher number of bone lesions at disease onset with a persistent course of disease more frequently.

Our results demonstrated an increased frequency of MEFV gene mutations in CNO and a more severe disease phenotype of CNO in patients with MEFV gene mutations. Physicians practicing in regions where FMF is prevalent should be aware of this relationship and ask about the symptoms of FMF in detail in patients with CNO. Moreover, FMF should be included in CNO-associated conditions.

Our results demonstrated an increased frequency of MEFV gene mutations in CNO and a more severe disease phenotype of CNO in patients with MEFV gene mutations. Physicians practicing in regions where FMF is prevalent should be aware of this relationship and ask about the symptoms of FMF in detail in patients with CNO. Moreover, FMF should be included in CNO-associated conditions.

Clinical improvement following tocilizumab (TCZ) therapy in patients with large-vessel (LVV) giant cell arteritis (GCA) is well established. However, information on TCZ effect on imaging vascular activity is limited. We aimed to determine if clinical improvement correlated with reduction of vascular 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET/CT) scans.

Observational study of patients with refractory LVV-GCA treated with TCZ who had a baseline and a follow-up 18F-FDG-PET/CT scan. For the visual analysis of 18F-FDG vascular uptake, a total vascular score (TVS) was defined, ranging from 0 to 15. Besides, a semiquantitative analysis was performed as a target to background ratio (TBR)= SUVmax thoracic aorta wall/SUVmax aortic vascular pool. The baseline and follow-up TVS and TBR were compared. Clinical and lab¬oratory outcomes were also assessed.

We included 30 patients (24 women/6 men); mean age± standard deviation 65.7± 9.8 years. Baseline PET/CT scans were performed due to active disease at a median [interquartile range-IQR] of 1.5 [0.0-4.0] months before TCZ onset. Following TCZ therapy, 25 (83.33%) patients achieved clinical remission and reduction of 18F-FDG vascular uptake was also observed after a mean ± standard deviation of 10.8±3.7 months. TBR decreased from 1.70 ± 0.52 to 1.48 ± 0.25 (p=0.005) and TVS from 4.97±2.62 to 3.13±1.89 (p< 0.001). However, only 9 (30.0%) patients showed complete normalisation of TBR and only 3 (10%) normalisation of TVS. TBR and TVS showed a good correlation (r=0.576).

Although most of LVV-GCA patients achieve clinical remission after TCZ therapy, less than one-third show normalisation of 18F-FDG vascular uptake.

Although most of LVV-GCA patients achieve clinical remission after TCZ therapy, less than one-third show normalisation of 18F-FDG vascular uptake.Psoriatic arthritis (PsA) is an inflammatory arthritis belonging to spondyloarthritides (SpA), a group of rheumatologic diseases characterised bya wide spectrum of different clinical manifestations that tend to associate with various comorbidities and that may significantly compromise the quality of life of patients. Nowadays, it is well known how PsA may manifest in different clinical domains, in particular peripheral articular and periarticular involvement, axial involvement, skin and nail psoriasis. Moreover, the majority of patients with PsA develop comorbidities such as inflammatory bowel diseases, uveitis, but also cardiovascular diseases, psychiatric or pulmonary pathologies. click here The therapeutical armamentarium of PsA has been enriched during the last years, in relation to an advance in the knowledge of the immunological mechanisms at the basis of the disease; in particular, the future frontier of "personalised medicine" could lead to a further improvement in the quality of care of this group of patients. In this paper we review the literature on PsA of 2019 (Medline search of articles published from 1st January 2019 to 31st December 2019).

Systemic sclerosis (SSc) is characterised by severe fibroproliferative vasculopathy, fibrosis in skin and multiple internal organs, and humoral, cellular and innate immunity abnormalities. Vascular alterations are the earliest and most severe SSc manifestations, however, the mechanisms responsible have remained elusive. To investigate the molecular abnormalities involved in SSc-vasculopathy we examined global gene expression differences between highly purified lung microvascular endothelial cells (MVECs) from patients with SSc-interstitial lung disease (SSc-ILD) and normal lung MVECs.

MVECs were isolated from fresh transplanted lungs from patients with SSc-ILD. Sequential CD31 and CD102 immunopurification was performed to obtain highly purified CD31+/CD102+ lung MVECs. Global gene expression analysis was successfully performed in CD31+/CD102+ MVEC from two SSc-ILD patients and from two normal lungs. RT-PCR, Western blots, and indirect immunofluorescence validated the gene expression results.

Numerous inerous IRGs and of genes encoding antiviral innate immune response and antiviral proteins. These observations suggest that interferon-induced and antiviral response proteins may participate in the pathogenesis of SSc vasculopathy and SSc-ILD. The CD31+/CD102+ lung MVECs from SSc-ILD also showed elevated expression of mesenchymal cell-specific genes confirming the presence of endothelial to mesenchymal transition in SSc-ILD.

The aims of this study were to investigate the development of new events (new clinical signs related to Behçet's disease) and to evaluate outcomes in juvenile Behçet's disease (jBD) patients over a 10-year follow-up.

We included 57 patients diagnosed with jBD according to International Behçet's Study Group (ISG) criteria and/or the International Criteria for BD (ICBD) and/or Paediatric BD (PEDBD) group criteria, followed-up between 2008 and 2018. Any new organ system involvement during follow-up was defined as an event in event-free survival analysis.

The patients' female/male ratio was 33/24. The most prevalent clinical feature was recurrent oral aphthosis (100%), followed by musculoskeletal symptoms (63%), genital ulcers (56%), ocular manifestations (47%) and cutaneous manifestations (46%). Vascular, neurological, gastrointestinal and genitourinary manifestations were observed in 4-17% of the patients. Fifty-four (95%) cases fulfilled the ICBD, while 31 (54%) and 34 (60%) fulfilled ISG and PEDBD criteria, respectively. The median Iranian Behçet's disease dynamic activity measure (IBDDAM) score at diagnosis was 5 (range 3-14) and decreased to 1 (range 0-6) at the last visit. One to three events occurred in 21 (37%) cases. One fifth (19%) of these events were severe. The event-free survival rate was 95% at one year, 70% at three years and 50% at eight years.

This study shows that with effective treatment, jBD has favourable outcome and a remarkable event-free survival. Underdiagnosed cases according to ISG and PEDBD criteria could be diagnosed using the ICBD.

This study shows that with effective treatment, jBD has favourable outcome and a remarkable event-free survival. Underdiagnosed cases according to ISG and PEDBD criteria could be diagnosed using the ICBD.