Correction to: Management of early ankle osteoarthritis through anterior joint-preserving surgery: a retrospective evaluation at mid- to long-term follow-up

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Hemorheological profiles and chronic inflammation markers in transfusion-dependent and non-transfusion- dependent thalassemia

: The rheological properties of blood play an important role in regulating blood flow in micro and macro circulation. In thalassemia syndromes red blood cells exhibit altered hemodynamic properties that facilitate microcirculatory diseases: increased aggregation and reduced deformability, as well as a marked increase in adherence to the vascular endothelial cells. A personalized approach to treating thalassemia patients (transfusions, iron chelation, and splenectomy), has increased patients' life expectancy, however they generally present many complications and several studies have demonstrated the presence of high incidence of thromboembolic events. In this study the hemorheological profiles of thalassemia patients have been characterized to point out new indices of vascular impairment in thalassemia. Plasma viscosity, blood viscosities at low and high shear rates (η1 and η200, respectively), erythrocyte aggregation index (η1/η200), and the erythrocyte viscoelastic profile (elastic modulus G', and viscous modulus G") have been studied in transfusion-dependent and non-transfusion-dependent thalassemia patients. Moreover, the levels of inflammation biomarkers in thalassemia have been evaluated to investigate a relationship between the biomarkers, the disease severity and the rheological parameters. The biomarkers studied are the main components of the immune and endothelial systems or are related to vascular inflammation: cytokines (IL-2, IL-6, IL-10, IL-17A, TNF-alpha), chemokines (IL-8, MIP-1alpha), adipocytokines (leptin and adiponectin), growth factors (VEGF, angiopoietin-1), adhesion molecules (ICAM-1, VCAM-1, E-selectin, L-selectin), and a monocyte/macrophage activation marker (CD163). This study shows that transfusion-dependent thalassemia patients, both major and intermedia, have blood viscosities comparable to those of healthy subjects. Non-transfusion-dependent thalassemia intermedia patients show high blood viscosities at low shear rates (η1), corresponding to the flow conditions of the microcirculation, an increase in erythrocyte aggregation, and high values of the elastic G' and viscous G" modules that reflect a reduced erythrocyte deformability and an increase in blood viscosity. Levels of cytokines, chemokines and adhesion molecules are different in transfusion- and non-transfusion dependent patients and positive correlations between η1 or η1/η200 and the cytokines IL-6 and IL-10 have been observed. The evaluation of the hemorheological profiles in thalassemia can provide new indicators of vascular impairment and disease severity in thalassemia in order to prevent the onset of thromboembolic events

Probabilistic and preferential sampling approaches offer integrated perspectives of Italian forest diversity

Aim: Assessing the performances of different sampling approaches for documenting community diversity may help to identify optimal sampling efforts and strategies, and to enhance conservation and monitoring planning. Here, we used two data sets based on probabilistic and preferential sampling schemes of Italian forest vegetation to analyze the multifaceted performances of the two approaches across three major forest types at a large scale. Location: Italy. Methods: We pooled 804 probabilistic and 16,259 preferential forest plots as samples of vascular plant diversity across the country. We balanced the two data sets in terms of sizes, plot size, geographical position, and vegetation types. For each of the two data sets, 1000 subsets of 201 random plots were compared by calculating the shared and exclusive indicator species, their overlap in the multivariate space, and the areas encompassed by spatially-constrained rarefaction curves. We then calculated an index of performance using the ratio between the additional and total information collected by each sampling approach. The performances were tested and evaluated across the three major forest types. Results: The probabilistic approach performed better in estimating species richness and diversity of species assemblages, but did not detect other components of the regional diversity, such as azonal forests. The preferential approach outperformed the probabilistic approach in detecting forest-specialist species and plant diversity hotspots. Conclusions: Using a novel workflow based on vegetation-plot exclusivities and commonalities, our study suggests probabilistic and preferential sampling approaches are to be used in combination for better conservation and monitor planning purposes to detect multiple aspects of plant community diversity. Our findings can assist the implementation of national conservation planning and large-scale monitoring of biodiversit

Alterations in Rev-ERBα/BMAL1 ratio and glycated hemoglobin in rotating shift workers: the EuRhythDia study

Objective: To detect premature gluco-metabolic defects among night shift workers with disturbances in circadian rhythms. Design and methods: We performed a hypothesis-generating, cross-sectional analysis of anthropometric, metabolic, lipid, and inflammation parameters, comparing active (a-NSW, n = 111) and former (f-NSW, n = 98) rotating night shift workers with diurnal workers (controls, n = 69). All participants were hospital nurses. We also evaluated the Pittsburgh Sleep Quality Index (PSQI) and assessed expression of transcription factors REV-ERBα and BMAL1 in peripheral blood mononuclear cells (PBMCs), as indicators of the molecular clock. Results: Both a-NSW and f-NSW participants had significantly higher glycated hemoglobin (HbA1c) and white blood cell counts (WBC) (p < 0.001 for both), PSQI global score (p = 0.001) and diastolic blood pressure levels (p = 0.024) compared with controls. Expression of REV-ERBα/BMAL1 RNA in PBMC was significantly higher in a-NSW (p = 0.05) than in f-NSW or control participants. Multivariate regression analysis showed that working status and PSQI were independent determinants of higher HbA1c levels (p < 0.001). Conclusions: We demonstrated that young, healthy night shift workers show subclinical abnormalities in HbA1c and changes in peripheral clock gene expression

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505

Extracorporeal life support in mitral papillary muscle rupture: Outcome of multicenter study

Background: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce.Methods: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications.Results: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group.Conclusions: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality

Kif13b Regulates PNS and CNS Myelination Through the Dlg1 Scaffold

Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS

New methods for thalassemia screening: TGA/chemometrics test is not influenced by the aging of blood samples

The coupling of Thermogravimetry (TG) in conjuction with chemometrics was investigated for the first time to evaluate the capabilities of this novel test to provide the screening of thalassemia in blood samples stored at 4 °C until 15 days. Healthy donors were considered as reference subjects and a typical thermal behaviour as a function of aging was estimated and compared to thermal behaviour of thalassemia subjects. Diagnosis of thalassemia was made at the Day-Hospital Thalassemia of S. Eugenio Hospital through a comprehensive assessment of clinical presentation and hematological and molecular analysis. Despite blood changes with aging, the application of the TGA/Chemometrics test reveal that healthy and thalassemic population may be significantly differentiated after 15 days from blood collection with a 100% of correct classification rate. This new method applied to aged samples was able to discriminate thalassemia in transfused patients that is generally not possible by the common first level protocol used for thalassemia screening, and in δβ-thalassemias, and β-thalassemia combined with Hb Lepore, usually requiring the molecular analysis for diagnosis. This study, for the first time, describes a screening method for thalassemia able to detect thalassemia on whole blood samples stored for 15 days. In conclusion TGA/Chemometrics screening test for thalassemia is not influenced by the aging of blood samples and this approach could open the way to prevention programs for thalassemia also in the developing countries where expertise and facilities for their control are extremely limited or in situation involving delayed analyses

Structural Characterization of Murine Phosphodiesterase 5 Isoforms and Involvement of Cysteine Residues in Supramolecular Assembly

Phosphodiesterases (PDEs) are a superfamily of evolutionarily conserved cyclic nucleotide (cAMP/cGMP)-hydrolyzing enzymes, components of transduction pathways regulating crucial aspects of cell life. Within this family, the cGMP-dependent PDE5 is the major hydrolyzing enzyme in many mammalian tissues, where it regulates a number of cellular and tissular processes. Using Kluyveromyces lactis as a model organism, the murine PDE5A1, A2 and A3 isoforms were successfully expressed and studied, evidencing, for the first time, a distinct role of each isoform in the control, modulation and maintenance of the cellular redox metabolism. Moreover, we demonstrated that the short N-terminal peptide is responsible for the tetrameric assembly of MmPDE5A1 and for the mitochondrial localization of MmPDE5A2. We also analyzed MmPDE5A1, A2 and A3 using small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), structural mass spectrometry (MS) and polyacrylamide gel electrophoresis in their native conditions (native-PAGE) and in the presence of redox agents. These analyses pointed towards the role of a few specific cysteines in the isoforms’ oligomeric assembly and the loss of enzymatic activity when modified

Piezosurgery in Hallux Valgus Correction: Distal Linear Osteotomy Operative Technique Using Piezoelectric Tools

Purpose \u2003Piezoelectric and ultrasonic vibrations have been used to cut tissues for three decades, in particular, in periodontics. The increasing use of piezosurgery is based on its clinical advantages such as selective cutting, precision, and low-temperature work rates. The authors applied this concept to a new operative field, the foot and ankle pathology and surgery, such as hallux valgus corrective distal linear osteotomy. Methods \u2003The osteotome equipped was the Surgysonic Moto-II model (Esacrom, Imola, Italy), a system recently developed for cutting bone withmicrovibrations. Tips used in author's case series were a high-efficiency five teeth piezoelectric saw and a high-efficiency flat scalpel shaped on three edges. Operative technique is described. Discussion and Conclusion \u2003Piezoelectric techniques were developed in response to the need for great precision and safety in bone surgery that was availavle with other manual and rmotorised instruments. Piezo-technology allows minimally-invasive and percutaneous surgery, with reduced trauma on periostium, bone, and soft tissues, reduced healing time of the osteotomy due to the absence of bony necrosis and debris formation and major precision