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

An investigation into CLIL-related sections of EFL coursebooks : issues of CLIL inclusion in the publishing market

The current ELT global coursebook market has embraced CLIL as a weak form of bilingual education and an innovative component to include in General English coursebooks for EFL contexts. In this paper I investigate how CLIL is included in ELT coursebooks aimed at teenaged learners, available to teachers in Argentina. My study is based on the content analysis of four series which include a section advertised as CLIL-oriented. Results suggest that such sections are characterised by (1) little correlation between featured subject specific content and school curricula in L1, (2) oversimplification of contents, and (3) dominance of reading skills development and lower-order thinking tasks. Through this study, I argue that CLIL components become superficial supplements rather than a meaningful attempt to promote weak forms of bilingual education

Shift-Volatility Transmission in East Asian Equity Markets

This paper attempts to provide evidence of "shift-volatility" transmission in the East Asian equity markets. By shift-volatility, we mean the volatility shifts from a low level to a high level, corresponding respectively to tranquil and crisis periods. We examine the interdependence of equity volatilities between Hong-Kong, Indonesia, Japan, Malaysia, the Philippines, Singapore, Thailand and the United States. Our main issue is whether shift-volatility needs to be considered as a regional phenomenon, or from a more global perspective. We find that the timing/spans of high volatility regimes correspond adequately to years historically documented as those of crises (the Asian crisis and the years following the 2008 crisis). Moreover, we suggest different indicators that could be useful to guide the investors in their arbitrage behavior in the different regimes: the duration of each state, the sensitivity of the volatility in a market following a change in the volatility in another market. Finally, we are able to identify which market can be considered as leading markets in terms of volatility

Macro-financial linkages and bank behaviour: evidence from the second-round effects of the global financial crisis on East Asia

This paper studies the link between macro-financial variability and bank behaviour, which justifies the second-round effects of the global financial crisis on East Asia. Following Gallego et al. (The impact of the global economic and financial crisis on Central Eastern and South Eastern Europe (CESEE) and Latin America, 2010), the second round effects are defined as the adverse feedback loop from the slumps in economic activities and sharp financial market deterioration, which may influence the financial performance of bank, inter alia via deteriorating credit quality, declining profitability and increasing problems in retaining necessary capitalization. Differentiating itself from other research, this study stresses adjustments in four dimensions of bank performance and behaviour: asset quality, profitability, capital adequacy, and lending behaviour, assuming that any change in a bank-specific characteristic is induced by endogenous adjustments of the others. The empirical results based on partial adjustment models and two-step system GMM estimation show that bank’s adjustment behaviour is subject to the variation in the macro-financial environment and the stress condition in the global financial market. There is no convincing evidence to support the effectiveness of policy rate cut to boots bank lending and to avoid a financial accelerator effect

New insights into Chlamydiae persistence: an energy metabolism strategy?

Chlamydiaceae is a family of obligate intracellular bacteria generally considered energy parasites. Several studies have suggested that Chlamydiae are capable of independently producing energy and, more importantly, several genes involved in the energy metabolism are up-regulated during the persistent state. Thus, it has been suggested that chlamydial persistence could be a complex and flexible metabolic strategy designed to favor a lengthy survival in the host cell by evading the immune response. In conclusion, more detailed studies on the shift in the chlamydial energy metabolism, from the active to the persistent form, may be helpful in future to determine whether chlamydial persistence observed in vitro does occur in vivo and whether chronic sequelae of chlamydial diseases may be related to the persistence

Neuroprotective Actions of Estradiol and Novel Estrogen Analogs in Ischemia: Translational Implications

This review highlights our investigations into the neuroprotective efficacy of estradiol and other estrogenic agents in a clinically relevant animal model of transient global ischemia, which causes selective, delayed death of hippocampal CA1 neurons and associated cognitive deficits. We find that estradiol rescues a significant number of CA1 pyramidal neurons that would otherwise die in response to global ischemia, and this is true when hormone is provided as a long-term pretreatment at physiological doses or as an acute treatment at the time of reperfusion. In addition to enhancing neuronal survival, both forms of estradiol treatment induce measurable cognitive benefit in young animals. Moreover, estradiol and estrogen analogs that do not bind classical nuclear estrogen receptors retain their neuroprotective efficacy in middle-aged females deprived of ovarian hormones for a prolonged duration (8 weeks). Thus, non-feminizing estrogens may represent a new therapeutic approach for treating the neuronal damage associated with global ischemia

The Minimal Clinically Important Difference Changes Greatly Based on the Different Calculation Methods

Background: The minimal clinically important difference (MCID) for patient-reported outcome measures (PROMs) expresses both the extent of the improvement and the value that patients place on it. MCID use is becoming increasingly widespread to understand the clinical efficacy of a given treatment, define guidelines for clinical practice, and properly interpret trial results. However, there is still large heterogeneity in the different calculation methods. Purpose: To calculate and compare the MCID threshold values of a PROM by applying various methods and analyzing their effect on the study results interpretation. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: The data set used to investigate the different MCID calculation approaches was based on a database of 312 patients affected by knee osteoarthritis and treated with intra-articular platelet-rich plasma. MCID values were calculated on the International Knee Documentation Committee (IKDC) subjective score at 6 months using 2 approaches: 9 methodologies referred to an anchor-based approach and 8 methodologies to a distribution-based approach. The obtained threshold values were applied to the same series of patients to understand the effect of using different MCID methods in evaluating patient response to treatment. Results: The different methods employed led to MCID values ranging from 1.8 to 25.9 points. The anchor-based methods ranged from 6.3 to 25.9, while the distribution-based ones were from 1.8 to 13.8 points, showing a 4.1× variation of the MCID values within the anchor-based methods and a 7.6× variation within the distribution-based methods. The percentage of patients who reached the MCID for the IKDC subjective score changed based on the specific calculation method used. Among the anchor-based methods, this value varied from 24.0% to 66.0%, while among the distribution-based methods, the percentage of patients reaching the MCID varied from 44.6% to 75.9%. Conclusion: This study proved that different MCID calculation methods lead to highly heterogeneous values, which significantly affect the percentage of patients achieving the MCID in a given population. The wide-ranging thresholds obtained with the different methodologies make it difficult to evaluate the real effectiveness of a given treatment questioning the usefulness of MCID, as currently available, in the clinical research

Total Knee Arthroplasty (TKA): When Do the Risks of TKA Overcome the Benefits? Double Risk of Failure in Patients up to 65 Years Old

Objective: The aim of this study was to document the survival rate in the middle-aged patient group up to 65 years old and to compare it with other age groups of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis (OA). Design: The Register of Orthopaedic Prosthetic Implants (RIPO) regional registry was used to analyze the results of patients <80 years old affected by primary OA and treated with TKA from 2000 to 2019. The database was investigated according to the age group: younger than 50 years, 50-65 years, or 66-79 years, with the aim to estimate revision surgeries and implant survivorship. Results: A total of 45,488 TKAs for primary OA were included in the analysis (M: 11,388; F: 27,846). The percentage of patients <65 years old increased from 13.5% to 24.8% between 2000 and 2019 (P < 0.0001). The survival analysis showed an overall influence of age on the implant revision rate (P < 0.0001), with an estimated survival rate of 78.7%, 89.4%, and 94.8% at 15 years in the 3 groups, respectively. Compared with the older-aged group, the relative risk of failure was 3.1 (95% confidence interval [CI] = 2.2-4.3; P < 0.001) higher in patients <50 years old and 1.8 (95% CI = 1.6-2.0; P < 0.001) higher in patients 50-65 years old. Conclusions: TKA use in the middle-aged patient population up to 65 years old increased significantly over time. These patients present a double risk of failure with respect to older patients. This is particularly important considering the increasing life expectancy and the emergence of new joint preserving strategies, which could postpone the need for TKA to an older age

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