The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Effect of different underhead shot-peening and lubrication conditions on high-strength screws undergoing multiple tightenings

This study investigates the effect of shot-peening on the bearing friction coefficient of 42CrMoV grade 14.9 screws. An experimental campaign was conducted on a tribological testing rig, investigating the combined effects of shot peening treatments, lubrication conditions, and number of tightenings on the frictional coefficient. A first set of tests was performed, considering the same shot-peening conditions as in a previous study to highlight the role of different material. A second campaign was carried out, adjusting the process parameters to enhance the tribological response. Small shots and high-impact energy are suitable for tightening with lubricant, whereas, in dry conditions, larger shots and lower-impact energy lead to particularly low friction coefficients that are well aligned to those achievable when using lubricants

Correlation Between Nurses' Caring Behaviors and Patients' Satisfaction

Background: Nowadays, the patients’ satisfaction is used as a criterion to measure the hospitals’ service quality. However, there are controversial results about the aspect of caring behaviors which mostly affects the patients’ satisfaction. Objectives: The current study aimed to assess the relationship between caring behaviors and patients’ satisfaction. Patients and Methods: A descriptive correlation study was conducted on 250 randomly selected patients in Beheshti Hospital in Kashan, Iran. A questionnaire was used to gather the data. Degree of satisfaction was measured on a five-point scale using the patient satisfaction instrument, and caring behavior was measured on a six-point scale by caring behavior inventory. Results: A significant positive correlation was observed between caring behavior mean score and that of the patient satisfaction (P < 0.001, r = 0.565). The subscale of “knowledge and professional skills” of the caring behavior inventory obtained the highest and the subscale of “respectful deference to others” got the lowest mean scores. In the patient satisfaction instrument, the two subscales of “technical - professional care” and “patient education” gained the highest and the lowest mean scores respectively. Conclusions: The caring behaviors of nurses and patient education can increase the patient satisfaction

Case Report: Anterior Cruciate Ligament Calcification in a Patient With Chondrocalcinosis: Micro-Computed Tomography Presentation

In this case report, an incidental postoperative diagnosis of anterior cruciate ligament (ACL) calcification, associated with calcification of posterior cruciate ligament (PCL) and lateral meniscus insertions, was made using micro-computed tomography (μCT) technology in a knee specimen obtained during a total knee replacement (TKR) surgery due to painful tri-compartmental osteoarthritis (OA) with chondrocalcinosis signs at preoperative X-ray. Anterior cruciate ligament calcification is an uncommon finding, and conventional X-ray and MRI are not so helpful in its identification. μCT scan, in contrast, is of interest because it provides highly spatial three-dimensional information with excellent visualization of bones and calcifications. The μCT technology used in this case report allowed us to perform a detailed analysis and a 3-D reconstruction of the calcium pyrophosphate dihydrate (CPPD) crystal deposition about the knee without the need to section the specimens into slice as performed in previous studies. The 3-D model obtained with μCT scan permits to gain more insight into the shape of the calcification within the fibers of the ligamentous structures of the joint

Effects of infill temperature on the tensile properties and warping of 3D-printed polylactic acid

Although extensive research has been carried out on the effects of temperature on the properties of parts by fused filament fabrication, no study considered the opportunity to use different temperatures and cooling strategies for the contour and the infill region. The purpose of this investigation is to explore such an opportunity through an experimental campaign on polylactic acid. Specifically, the variations in tensile properties and warping occurring with different infill temperatures and cooling methods are documented. The results demonstrate that diversifying process parameters used for the contour and infill of the part allow for significant improvements in mechanical properties without affecting the distortion of the manufactured samples. This result can be achieved by either increasing the nozzle temperature or switching off the cooling fan during infilling

Community action projects: community-engaged quality improvement for medical students.

BACKGROUND: Healthcare Quality Improvement (QI) is an essential skill for medical students to acquire, although there is insufficient empirical research which suggests the best educational methods to do this. This study explored the experiences of medical students participating in two versions of a Community Action Project (CAP) which gave medical students the opportunity to learn QI skills in a community setting. The first version (GPCAP) was pre-pandemic where students identified and delivered QI projects on placement in general practice to improve local population health. The second version (Digi-CAP) ran remotely where students worked on QI projects identified by local voluntary sector organisations focused on local community priorities during COVID-19. METHODS: Semi-structured interviews were conducted with volunteers from the two cohorts of students who had taken part in quality improvement initiatives. Transcriptions were independently coded by two researchers and analysed through thematic analysis. RESULTS: Sixteen students were interviewed. Whilst students had mixed experiences of completing their CAP, engagement and successful learning was associated with the following themes from the two versions of QI CAP projects: finding a sense of purpose and meaning in QI projects; preparedness for responsibility and service-driven learning; the importance of having supportive partnerships throughout the project duration and making a sustainable difference. CONCLUSIONS AND IMPLICATIONS: The study provides valuable insights into the design and implementation of these community-based QI projects, which enabled students to learn new and often hard to teach skills, whilst working on projects which have a sustainable impact on local community outcomes

On the impact strength of adhesive bonded pin-and-collar joints

Nowadays, the adhesive technology is gaining relevance in industrial sectors where impact operating conditions are very common. At the same time, tests on cylindrical joints represent a well-established method for determining the static strength of structural adhesives. This work aims at assessing the impact properties of structural adhesives by means of cylindrical joints. The investigation involved two adhesive formulations (an epoxy resin and an anaerobic) and has been carried out under static, quasi-static and low-velocity impact conditions. The main outcomes of the work are: (i) the pin-collar specimen is well suited to analyzing the impact properties of adhesives; (ii) both adhesives showed a dependence of the strength and stiffness properties on the strain rate; (iii) the epoxy product showed a greater impact toughness than the anaerobic. In appendix, the authors report the tuning procedure of a CZM numerical model in a commercial FE package, based on the experimental results

Effect of the Position in the Build Chamber on the Fatigue Strength of Additively Manufactured Maraging Steel MS1

The quality of additively produced parts and the achievable mechanical response may be affected by several factors, such as build orientation, heat treatment, or machining. A further rarely investigated factor is the position of the built part in the chamber with respect to inert gas flow. Previous studies have highlighted that the interaction between gas flow and laser track may induce an intense vaporization with consequent lack of fusion, particle entrainment, drop in density and denudation of the produced part, which is likely to detrimentally affect mechanical properties. This study addresses the effect of part position on the fatigue strength of heat-treated maraging steel MS1 produced by an EOSINT M280 machine in a nitrogen environment. Novelty arises from the lack of studies in this field, especially under fatigue. A factorial plan with subsequent statistical analysis highlighted that positioning the part upstream with respect to the gas flow leads to a slightly lower fatigue strength; however, no significant differences are observed. The failure mode, involving initiation from subsurface porosities of the same size, is also unaffected. Finally, a fatigue limit of 26% of the ultimate tensile strength is found, which is consistent with previous outcomes

Design and Optimization of a Pneumatic Clamping System for Direct-Driven Rotary Tables

Modern direct-driven and high-speed rotary tables with torque motor are optimally suited for all handling and assembly applications that require the shortest indexing times and flexible positioning. The following paper is devoted to the study, the design, and the optimization of an innovative table clamping system (brake for accurate positioning) actuated by pneumatic energy, working at a maximum clamping pressure of 6 bar. The challenge for the aforementioned application is related to developing a solution able to provide a maximum tangential torque (with clamping actuated) in the range of thousands of Nm without leveraging the use of high-pressure hydraulic energy. The optimization of the proposed solution is based on the precise calculation of the stresses in order to perform a fatigue assessment and on the elastic deformation of the clamps in order to set the correct tolerances between the mating parts. Eventually, an experimental campaign is carried out in order to tune the numerical model, which is then used to validate the proposed design solution