Regenerated silk fibroin scaffold and infrapatellar adipose stromal vascular fraction as feeder-layer: a new product for cartilage advanced therapy

Articular cartilage has limited repair and regeneration potential, and the scarcity of treatment modalities has motivated attempts to engineer cartilage tissue constructs. The use of chondrocytes in cartilage tissue engineering has been restricted by the limited availability of these cells, their intrinsic tendency to lose their phenotype during the expansion, as well as the difficulties during the first cell adhesion to the scaffold. Aim of this work was to evaluate the intra-articular adipose stromal vascular fraction attachment on silk fibroin scaffold to promote chondrocytes adhesion and proliferation. Physicochemical characterization has demonstrated that three-dimensionally organized silk fibroin scaffold is an ideal biopolymer for cartilage tissue engineering; it allows cell attachment, scaffold colonization, and physically cell holding in the area that must be repaired; the use of adipose-derived stem cells is a promising strategy to promote adhesion and proliferation of chondrocytes to the scaffold as an autologous human feeder layer.     

Electrospun scaffolds of self-assembling peptides with poly(ethylene oxide) for bone tissue engineering

Structural, mechanical and biochemical properties have to be considered when searching for suitable extracellular matrix substitutes. Fibrous structures of synthetic or natural polymers have received increasing interest as three-dimensional scaffolds for tissue engineering applications as they can be easily produced by electrospinning with different topographical features by changing the process parameters. On the other hand, the nanobiotechnology approach suggests mimicking molecular architectures in nature through self-assembly. In particular, self-assembling peptide-based biomaterials have been successfully used as scaffolds for cell growth. In order to amalgamate these two strategies nanofibrous electrospun scaffolds of hybrid polymer were designed and obtained by mixing poly(ethylene oxide) and self-assembling peptides in aqueous solution. The results of in vitro osteoblast adhesion and proliferation assays on the electrospun scaffolds obtained using different self-assembling peptide sequences are discussed.     

Intraflagellar transport: a new player at the immune synapse

The assembly and maintenance of primary cilia, which orchestrate signaling pathways centrally implicated in cell proliferation, differentiation and migration, are ensured by multimeric protein particles in a process known as intraflagellar transport (IFT). It has recently been demonstrated that a number of IFT components are expressed in hematopoietic cells, which have no cilia. Here, we summarize data for an unexpected role of IFT proteins in immune synapse assembly and intracellular membrane trafficking in T lymphocytes, and discuss the hypothesis that the immune synapse could represent the functional homolog of the primary cilium in these cells.     

Comparative classification of thrombotic formations on bileaflet mechanical heart valves by phonographic analysis

Haemodynamic performance of bileaflet mechanical heart valves can be severely affected by the formation of thrombotic deposits. Hence, early detection of thrombi is fundamental for a prompt diagnosis and adequate therapy. This article aims at designing a novel diagnostic and prognostic tool able to detect valvular thrombosis at early stages of formation, i.e., before the appearance of critical symptoms in patients who can be effectively treated by pharmacological therapy, preventing re-operation. This approach relies on the acquisition of the acoustic signals produced by mechanical heart valves in the closing phase; the corresponding power spectra are then analysed by means of artificial neural networks trained to identify the presence of thrombi and classify their occurrence. Five commercial bileaflet mechanical heart valves were investigated in vitro in a Sheffield Pulse Duplicator; for each valve six functional conditions were considered, each corresponding to a risk class for patients (one normofunctioning and five thrombosed): they have been simulated by placing artificial deposits of increasing weight and different shape on the valve leaflet and on the annular housing; the case of one completely blocked leaflet was also investigated. These six functional conditions represent risk classes: they were examined under various hydrodynamic regimes. The acoustic signals produced by the valves were acquired by means of a phonocardiographic apparatus, then analysed and classified. The ability to detect and classify thrombotic formations on mechanical valve leaflet would allow ranking patients by assigning them to one of the six risk classes, helping clinicians in establish adequate therapeutic approaches.     

HIV-2 A-subtype gp125c₂-v₃-c₃ mutations and their association with CCR5 and CXCR4 tropism

The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125_C2-V3-C3 mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5- and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.     

Wilms tumor in patients with osteopathia striata with cranial sclerosis

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15–30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith–Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.Subject terms: Genetics, Clinical genetics, Disease genetics     

Early predictors of mortality in refractory cardiogenic shock following acute coronary syndrome treated with extracorporeal membrane oxygenator

We aimed to analyze the outcome and identify predictors of hospital mortality in patients with refractory cardiac arrest (CA) complicating acute coronary syndromes (ACS) and requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Between Jan-2005 and Dec-2019, 51 patients underwent urgent VA-ECMO implantation for CA in ACS. Patients were divided in two groups: “in-hospital” cardiac arrest (IHCA) and “out-of-hospital” cardiac arrest (OHCA). Prospectively collected data were retrospectively analyzed and compared between groups. Predictors for hospital mortality were investigated. IHCA and OHCA patients were 32 (62.7%) and 19 (37.3%), respectively. The groups differed for: male gender (72% vs 95%; p?=?0.070), lactate peak level (8.5?±?4.3vs10.7?±?2.9; p?=?0.023), total elapsed time from CA to VA-ECMO implantation in both groups (p?<?0.001) and elapsed time from CA (IHCA group) or hospital arrival (OHCA group) to VA-ECMO implantation (38 min vs 80 min; p?=?0.001). At logistic regression analysis, concomitant lactate level greater than 8.0 mmol/L and elapsed time from CA to VA-ECMO?≥?30 min were predictors of increased mortality (OR 3.9; 95% CI 1.19–12.79; p?=?0.025) for the entire population. In-hospital mortality was 60.8% (31/51 patients): 68.4% in OHCA group and 56.2% in IHCA group. No risk factors related to 30-day mortality resulted significant at univariable analysis. When rapidly instituted, VA-ECMO improves survival in patients with refractory cardiac arrest allowing coronary syndrome treatment. The association of an elapsed time from CA to VA-ECMO implantation longer than 30 min and a preoperative lactate peak level over 8.0 mmol/L predict a poor outcome, independently from being IHCA or OHCA.

     

A novel MEIS2 mutation explains the complex phenotype in a boy with a typical NF1 microdeletion syndrome

Concurrence of distinct genetic conditions in the same patient is not rare. Several cases involving neurofibromatosis type 1 (NF1) have recently been reported, indicating the need for more extensive molecular analysis when phenotypic features cannot be explained by a single gene mutation. Here, we describe the clinical presentation of a boy with a typical NF1 microdeletion syndrome complicated by cleft palate and other dysmorphic features, hypoplasia of corpus callosum, and partial bicoronal craniosynostosis caused by a novel 2bp deletion in exon 2 of Meis homeobox 2 gene (MEIS2) inherited from the mildly affected father. This is only the second case of an inherited MEIS2 intragenic mutation reported to date. MEIS2 is known to be associated with cleft palate, intellectual disability, heart defects, and dysmorphic features. Our clinical report suggests that this gene may also have a role in cranial morphogenesis in humans, as previously observed in animal models.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.