Active Materials for 3D Printing in Small Animals: Current Modalities and Future Directions for Orthopedic Applications

The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary medicine, because of the wide range of dimensions and anatomical variances, receiver-specific diagnosis and therapy are even more critical. The ability to generate 3D anatomical models and customize orthopedic instruments, implants, and scaffolds are advantages of 3D printing in small animal orthopedics. Furthermore, this technology provides veterinary medicine with a powerful tool that improves performance, precision, and cost-effectiveness. Nonetheless, the individualized 3D-printed implants have benefited several complex orthopedic procedures in small animals, including joint replacement surgeries, critical size bone defects, tibial tuberosity advancement, patellar groove replacement, limb-sparing surgeries, and other complex orthopedic procedures. The main purpose of this review is to discuss the application of 3D printing in small animal orthopedics based on already published papers as well as the techniques and materials used to fabricate 3D-printed objects. Finally, the advantages, current limitations, and future directions of 3D printing in small animal orthopedics have been addressed.     

The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance

Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions?     

Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, α_IIbβ₃, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet–neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet–monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.     

Targeting the DNA Damage Response to Increase Anthracycline-Based Chemotherapy Cytotoxicity in T-Cell Lymphoma

Mature T-cell lymphomas (MTCLs) represent a heterogeneous group of aggressive non-Hodgkin lymphomas comprising different entities. Anthracycline-based regimens are considered the standard of care in the front-line treatment. However, responses to these approaches have been neither adequate nor durable, and new treatment strategies are urgently needed to improve survival. Genomic instability is a common feature of cancer cells and can be caused by aberrations in the DNA damage response (DDR) and DNA repair mechanisms. Consistently, molecules involved in DDR are being targeted to successfully sensitize cancer cells to chemotherapy. Recent studies showed that some hematological malignancies display constitutive DNA damage and intrinsic DDR activation, but these features have not been investigated yet in MTCLs. In this study, we employed a panel of malignant T cell lines, and we report for the first time the characterization of intrinsic DNA damage and basal DDR activation in preclinical models in T-cell lymphoma. Moreover, we report the efficacy of targeting the apical kinase ATM using the inhibitor AZD0156, in combination with standard chemotherapy to promote apoptotic cell death. These findings suggest that DDR is an attractive pathway to be pharmacologically targeted when developing novel therapies and improving MTCL patients’ outcomes.     

Campylobacter jejuni loss of culturability in aqueous microcosms and ability to resuscitate in a mouse model

Water is known as one of the main transmission routes of Campylobacter and contributes to increase the number of sporadic infections and outbreaks. Campylobacter jejuni persists in the environment, especially in water, in a viable but non-culturable (VBNC) form that is thought to be a possible cause of water-borne outbreaks. In this study, we evaluated the loss of culturability and viability of 9 C. jejuni strains of clinical origin and one ATCC reference strain when kept at 4 degrees C in artificial sea water (ASW). Culturability was measured as colony-forming units while viability was evaluated by CTC-DAPI double staining and the combined CTC-specific fluorescent antibody technique (CTC-FA). When cultured on Columbia Agar plates, strains exhibited different growth profiles which allowed to classify them into three different groups. Both techniques used to monitor the viability of the bacterial cells showed that C. jejuni strains survived in the VBNC form in the microcosms through a period lasting from 138 to 152 days. The recovery of C. jejuni VBNC forms to culturability, as evidenced by cell division, was obtained by passage in the mouse intestine. Our results indicate that C. jejuni VBNC cells were able to remain in this state for a few months and regain their culturability after in vivo passage depending on their lasting in the VBNC state, which affects the number of respiring bacteria. In fact, the resuscitation was achieved when the number of respiring bacteria became higher than 10(4) cell/ml. Therefore, a relatively high microbial titer of respiring bacteria in the VBNC state seems to be important for the resuscitation and subsequent intestinal colonisation.     

昨天/明天: 意大利城市保护与发展50年

本文记录了意大利城市保护的理论和文化信息,更重要的是,它展示了由城市和区域部门执行的具体保护案例,并展示了大学研究中心在保护技术和方法上的进步。主要分为4个部分：历史、城市议题、景观议题、培训和国际合作。从城市设计的理念和技术的角度,向世人解析意大利古罗马建筑如何在现代化城市进程中愈加焕发时尚气息的领先技术。中国现阶段正经历着经济快速发展所带来的种种迷惑,或许能从分享中找到答案。     

Gel mechanical properties of milk whey protein–dextran conjugates obtained by Maillard reaction

The effect of Maillard reaction on the mechanical properties of whey protein isolate (WPI) heat-induced gels was evaluated. WPI and dextran (15–25 kDa) conjugates were obtained by controlled dry heating during storage at 60 °C and 63% relative humidity for 2, 5 and 9 days. Changes in browning intensity and content of free amino groups were used to estimate the Maillard reaction. A decrease in free amino groups of WPI was observed when increasing polysaccharide concentration and reaction time. An increase in both a* and b* CIE Lab colour parameters indicated the development of a reddish-brown colour, typical of the Maillard reaction. Uniaxial compression and stress relaxation tests were performed to measure the mechanical properties of mixed and conjugate gels. Maillard reaction significantly modified the mechanical properties of WPI/DX gels, and even prevented fracture when conjugate gels were subjected to 80% deformation in uniaxial compression test.