Infectious agents in atherosclerotic cardiovascular diseases through oxidative stress

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research

Complications of Tranexamic Acid in Orthopedic Lower Limb Surgery: A Meta-Analysis of Randomized Controlled Trials

Objective. Tranexamic acid (TXA) is increasingly used in orthopedic surgery to reduce blood loss; however, there are concerns about the risk of venous thromboembolic (VTE) complications. The aim of this study was to evaluate TXA safety in patients undergoing lower limb orthopedic surgical procedures. Design. A meta-analysis was performed on the PubMed, Web of Science, and Cochrane Library databases in January 2020 using the following string (Tranexamic acid) AND ((knee) OR (hip) OR (ankle) OR (lower limb)) to identify RCTs about TXA use in patients undergoing every kind of lower limb surgical orthopedic procedures, with IV, IA, or oral administration, and compared with a control arm to quantify the VTE complication rates. Results. A total of 140 articles documenting 9,067 patients receiving TXA were identified. Specifically, 82 studies focused on TKA, 41 on THA, and 17 on other surgeries, including anterior cruciate ligament reconstruction, intertrochanteric fractures, and meniscectomies. The intravenous TXA administration protocol was studied in 111 articles, the intra-articular in 45, and the oral one in 7 articles. No differences in terms of thromboembolic complications were detected between the TXA and control groups neither in the overall population (2.4% and 2.8%, respectively) nor in any subgroup based on the surgical procedure and TXA administration route. Conclusions. There is an increasing interest in TXA use, which has been recently broadened from the most common joint replacement procedures to the other types of surgeries. Overall, TXA did not increase the risk of VTE complications, regardless of the administration route, thus supporting the safety of using TXA for lower limb orthopedic surgical procedures

Electrochemical incineration of oxalic acid in the presence of NaCl

Recent researches have demonstrated that electrochemical methods offer an attractive alternative to traditional routes for treating wastewaters containing toxic or/and refractory organic pollutants. The effectiveness of the electrochemical treatment depends on many factors including the presence in solution of specie able to act as mediators. In particular, the effect of chloride ions on the performances of the process has been the object of numerous researches. However, up to now, many practical and theoretical aspects about this argument are not completely clear. In the present work, the anodic incineration of oxalic acid (OA) in the presence of NaCl has been investigated with the aim of studying in a systematic way the influence of numerous parameters, such as the current density, the flow rate, the OA, the NaCl concentrations and the pH on the performances of the process and to individuate the optimal operative conditions. Oxalic acid was chosen as model substrate for its low reactivity toward anodic oxidation, which also results in an incomplete mineralization of more complex organics. Furthermore, the oxidation of this simple molecule does not involve the formation of stable intermediates thus giving rise to a more easy rationalizing of experimental results. Since the effect of NaCl on the process is expected to depend on the nature of the electrodic material, two very different anodes were used: the Ti/IrO2-Ta2O5 which presents a quite low oxygen overpotential and boron doped diamond (BDD) which is probably one of the more promising materials for the electrochemical incineration

Extra virgin olive oil-based formulations. A "green" strategy against Chlamydia trachomatis

In recent decades, antibiotic misuse has emerged as an important risk factor for the appearance of multi-drug-resistant bacteria, and, recently, antimicrobial resistance has also been described in Chlamydia trachomatis as the leading cause of bacterial sexually transmitted diseases worldwide. Herein, we investigated, for the first time, the antibacterial activity against C. trachomatis of a polyphenolic extract of extra virgin olive oil (EVOO), alongside purified oleocanthal and oleacein, two of its main components, in natural deep eutectic solvent (NaDES), a biocompatible solvent. The anti-chlamydial activity of olive-oil polyphenols (OOPs) was tested in the different phases of chlamydial developmental cycle by using an in vitro infection model. Transmission and scanning electron microscopy analysis were performed for investigating potential alterations of adhesion and invasion, as well as morphology, of chlamydial elementary bodies (EBs) to host cells. The main result of our study is the anti-bacterial activity of OOPs towards C. trachomatis EBs down to a total polyphenol concentration of 1.7 µg/mL, as shown by a statistically significant decrease (93.53%) of the total number of chlamydial-inclusion-forming units (p < 0.0001). Transmission and scanning electron microscopy analysis supported its anti-chlamydial effect, suggesting that OOP might damage the chlamydial outer layers, impairing their structural integrity and hindering EB capability to infect the host cell. In conclusion, OOPs may represent an interesting alternative therapeutic option toward C. trachomatis, although further studies are necessary for exploring its clinical applications

Minimum 10-Year Clinical Outcome of Lateral Collagen Meniscal Implants for the Replacement of Partial Lateral Meniscal Defects: Further Results From a Prospective Multicenter Study

Background: The collagen meniscal implant (CMI) is a biologic scaffold aimed at replacing partial meniscal defects. The long-term results of lateral meniscal replacement have never been investigated. Purpose: To document the clinical outcomes and failures of lateral CMI implantation for partial lateral meniscal defect at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4, Methods: This study included 24 consecutive patients who underwent lateral CMI implantation for partial lateral meniscal defects between April 2006 and September 2009 and who were part of a previous study with a 2-year follow-up. Outcome measures at the latest follow-up included the Lysholm score, Knee injury and Osteoarthritis Outcome Score, visual analog scale (VAS) for pain, Tegner activity level, and EuroQol 5-Dimensions score. Data regarding complications and failures were collected, and patients were asked about their satisfaction with the procedure. Results: Included in the final analysis were 19 patients (16 male, 3 female) with a mean age at surgery of 37.1 ± 12.6 years and a mean follow-up of 12.4 ± 1.5 years (range, 10-14 years). Five failures (26%) were reported: 1 CMI removal because of implant breakage and 4 joint replacements (2 unicompartmental knee arthroplasties and 2 total knee arthroplasties). The implant survival rate was 96% at 2 years, 85% at 5 years, 85% at 10 years, 77% at 12 years, and 64% at 14 years. Lysholm scores at the final follow-up were rated as “excellent” in 36% (5 of 14 nonfailures), “good” in 43% (6 of 14), and “fair” in 21% (3 of 14). The VAS score was 3.1 ± 3.1, with only 16% (3 of 19 patients) reporting that they were pain-free; the median Tegner score was 3 (interquartile range, 2-5). All clinical scores decreased from the 2-year follow-up; however, with the exception of the Tegner score, they remained significantly higher compared with the preoperative status. Overall, 79% of patients were willing to undergo the same procedure. Conclusion: Lateral CMI implantation for partial lateral meniscal defects provided good long-term results, with a 10-year survival rate of 85% and a 14-year survival rate of 64%. At the final follow-up, 58% of the patients had “good” or “excellent” Lysholm scores. However, there was a general decrease in outcome scores between the short- and the long-term follow-up

Polyamine supplementation reduces DNA damage in adipose stem cells cultured in 3-D

According to previous research, natural polyamines exert a role in regulating cell committment and differentiation from stemness during skeletal development. In order to assess whether distinct polyamine patterns are associated with different skeletal cell types, primary cultures of stem cells, chondrocytes or osteoblasts were dedicated for HPLC analysis of intracellular polyamines. Spermine (SPM) and Spermidine (SPD) levels were higher in adipose derived stem cells (ASC) compared to mature skeletal cells, i.e. chondrocytes and osteoblasts, confirming the connection of polyamine content with stemness. To establish whether polyamines can protect ASC against oxidative DNA damage in a 3-D differentiation model, the level of gamma H2AX was measured by western blot, and found to correlate with age and BMI of patients. Addition of either polyamine to ASC was able to hinder DNA damage in the low micromolecular range, with marked reduction of gamma H2AX level at 10 mu M SPM and 5 mu M SPD. Molecular analysis of the mechanisms that might underlie the protective effect of polyamine supplementation evidences a possible involvement of autophagy. Altogether, these results support the idea that polyamines are able to manage both stem cell differentiation and cell oxidative damage, and therefore represent appealing tools for regenerative and cell based applications

Minimal Clinically Important Difference and Patient Acceptable Symptom State in Patients With Knee Osteoarthritis Treated With PRP Injection

Background: Although several injection-based treatments have been proposed to address knee osteoarthritis (OA), it is often difficult to understand the clinical relevance of the obtained results. The psychometric measures of minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were developed to better interpret study findings. Purpose: To establish the MCID and the PASS for the International Knee Documentation Committee (IKDC) Subjective score and the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients treated with intra-articular platelet-rich plasma (PRP) injections for knee OA. Study Design: Case series; Level of evidence, 4. Methods: This study included 215 patients with knee OA (68% men, 32% women; age, 53.2 ± 11.3 years; body mass index, 26.8 ± 4.3 kg/m2) who underwent intra-articular PRP injections. Patients were assessed through the IKDC Subjective score and KOOS subscales, and the MCID and the PASS for both measures were independently calculated at 6 and 12 months post-injection. The MCID was calculated using the value equal to half of the standard deviation of the overall cohort improvement. The PASS was assessed using a 2-point scale (satisfied or not satisfied), with threshold values being detected through a receiver operating characteristic curve analysis and the Youden index to maximize the sensitivity and the specificity of the threshold values. Results: All scores improved significantly from baseline to 6 months and baseline to 12 months (P <.001 for all scores). All scores were stable from 6 to 12 months except for the KOOS Quality of Life subscale, which improved further (P =.033). For the IKDC, the MCID values were 8.6 and 8.5 points and the PASS scores were 59.7 and 62.1 at 6 and 12 months, respectively. Overall, the MCID and the PASS for all KOOS subscales remained constant at the 2 follow-up points. The percentage of patients who achieved the MCID and the PASS was higher than 85% at both 6 and 12 months post-injection. Conclusion: This study provided the MCID and PASS thresholds for the IKDC and KOOS scores in patients with knee OA treated with PRP injections. These psychometric measures may allow a better interpretation of the clinical relevance of injection-based treatment outcomes for knee OA

CHERIvoke: Characterising pointer revocation using CHERI capabilities for temporal memory safety

A lack of temporal safety in low-level languages has led to an epidemic of use-after-free exploits. These have surpassed in number and severity even the infamous buffer-overflow exploits violating spatial safety. Capability addressing can directly enforce spatial safety for the C language by enforcing bounds on pointers and by rendering pointers unforgeable. Nevertheless, an efficient solution for strong temporal memory safety remains elusive. CHERI is an architectural extension to provide hardware capability addressing that is seeing significant commercial and open- source interest. We show that CHERI capabilities can be used as a foundation to enable low-cost heap temporal safety by facilitating out-of-date pointer revocation, as capabilities enable precise and efficient identification and invalidation of pointers, even when using unsafe languages such as C. We develop CHERIvoke, a technique for deterministic and fast sweeping revocation to enforce temporal safety on CHERI systems. CHERIvoke quarantines freed data before periodically using a small shadow map to revoke all dangling pointers in a single sweep of memory, and provides a tunable trade-off between performance and heap growth. We evaluate the performance of such a system using high-performance x86 processors, and further analytically examine its primary overheads. When configured with a heap-size overhead of 25%, we find that CHERIvoke achieves an average execution-time overhead of under 5%, far below the overheads associated with traditional garbage collection, revocation, or page-table systems.EP/K026399/1, EP/P020011/1, EP/K008528/

Higher 90-day mortality after surgery for hip fractures in patients with covid-19: A case–control study from a single center in italy

The mortality of hip fracture (HF) patients is increased by concomitant COVID-19; however, evidence is limited to only short follow-up. A retrospective matched case–control study was designed with the aim to report the 90-day mortality and determine the hazard ratio (HR) of concomitant HF and COVID-19 infection. Cases were patients hospitalized for HF and diagnosed with COVID-19. Controls were patients hospitalized for HF not meeting the criteria for COVID-19 diagnosis and were individually matched with each case through a case–control (1:3) matching algorithm. A total of 89 HF patients were treated during the study period, and 14 of them were diagnosed as COVID-19 positive (overall 15.7%). Patients’ demographic, clinical, and surgical characteristics were similar between case and control groups. At 90 days after surgery, 5 deaths were registered among the 14 COVID-19 cases (35.7%) and 4 among the 42 HF controls (9.5%). COVID-19-positive cases had a higher risk of mortality at 30 days (HR = 4.51; p = 0.0490) and 90 days (HR = 4.50; p = 0.025) with respect to controls. Patients with concomitant HF and COVID-19 exhibit high perioperative mortality, which reaches a plateau of nearly 30–35% after 30 to 45 days and is stable up to 90 days. The mortality risk is more than four-fold higher in patients with COVID-19