Crabtreevance1775
Overall, the results demonstrate that chronic DLM exposure induces kidney apoptosis and fibrosis via inhibition of the Nrf2/p38MAPK pathway. This study provides a new understanding for the mechanism of DLM-induced quail kidney injury and also provides a theoretical basis for treatment of the DLM poisoning.
Paclitaxel-eluting devices (PED) reduce restenosis and target lesion revascularization (TLR) in femoropopliteal intervention. Recent data suggest a two-fold increased long-term mortality in patients treated with PED. The aim of our study is to evaluate if endovascular therapy (EVT) with PED increases mortality risk in patients with symptomatic lower limb peripheral artery disease (PAD) compared to non-eluting devices (NED).
The study is a retrospective, single-center registry on patients undergoing EVT for PAD from January 2009 to June 2018. Propensity score analysis on logistic regression model for independent predictors of long-term mortality was used to match PED and NED patients. Mortality was assessed at 2, 5 and 7years in the entired matched population and in a sub-group of patients ≤75years.
During the study period, 1294 patients, 718 NED and 576 PED, met the inclusion/exclusion criteria and entered in the study. Propensity score matching analysis identified 854 matched patients, 414 PED and 440 NED. The population was mainly characterized by diabetic patients with CLI (80%) and high prevalence of CAD (30%), heart failure (15%) and renal insufficiency (20%). Mean follow-up length was 58±34months, (median 52.5). Mortality was 18% in NED vs 12% in PED patients at two years (p=0.01), 36% vs 30% at 5years (p=0.03) and 41% vs 39% at seven years (p=0.2) respectively. In patients ≤75years, mortality at 7-year was 28% in PED vs 36% in NED, p=0.07.
These results suggest a reduced mortality at 2 and 5years with PED as compare to NED treatment in a real-world CLI scenario. At 7-year follow-up, the advantage was numerically evident only in patients ≤75years.
These results suggest a reduced mortality at 2 and 5 years with PED as compare to NED treatment in a real-world CLI scenario. At 7-year follow-up, the advantage was numerically evident only in patients ≤75 years.
We aimed to evaluate the trajectory of two surrogates of fluid overload -antigen carbohydrate 125 (CA125) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)- after the addition of oral empagliflozin to usual care in a cohort of patients with chronic heart failure (CHF) and type 2 diabetes (T2D).
From October 2015 to February 2019, 60 ambulatory patients with CHF and T2D were retrospectively included. The primary endpoint was to assess the longitudinal trajectory of plasma levels of CA125 and NT-proBNP after empagliflozin initiation. Changes in quantitative variables were evaluated using linear mixed regression. Median CA125 and NT-proBNP at baseline were 17 (11-75) U/mL and 1662 (647-4230) pg/mL, respectively. A total of 510 outpatient visits were recorded [median (interquartile range) of visits per patient 6 (4-11)] during a median of 1.78 years. We found a significant and steady decrease in the log of CA125 after empagliflozin initiation (p < 0.001). Conversely, the log of NT-proBNP predicted trajectory did not significantly change (p = 0.425).
In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion.
In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion.
In the neurosciences, the physical disector method represents an established quantitative stereological method for unbiased sampling and counting of cells in histological tissue sections of known thickness. Physical disector analyses are conventionally performed using plastic-embedded tissue samples, because plastic-embedding causes a comparably low and definable shrinkage of the embedded tissue, and the thickness of thin plastic sections can be determined adequately. However, immunohistochemistry protocols often don't work satisfactorily in sections of plastic-embedded tissue.
Here, a new methodological approach is presented, allowing for physical disector analyses of immunohistochemically labeled cells in paraffin sections. The embedding-related tissue shrinkage is standardized by using defined tissue sample volumes and paraffin volumes, and the extent of tissue shrinkage can be determined accurately from the sample volumes prior to and after embedding. Co-embedding of polyethylene section thickness staell types.Mass media extensively inform societies about events threatening the global food supply (e.g., pandemics or Brexit). Consumers exposed to such communication may perceive food resources as becoming scarcer. In line with an evolutionary account, these perceptions can shift decision-making in domains such as food preferences or prosociality. However, existing literature has solely focused on actual and past food insecurity experiences threatening mostly low-income families, thus neglecting the future-oriented perceptions among the general population. This paper broadens the food insecurity research scope by developing a new construct-anticipated food scarcity (AFS)-which is defined as the perception that food resources are becoming less available (in the future). We have developed and psychometrically validated the 8-item Anticipated Food Scarcity Scale (AFSS) in eight studies (N = 1333). The 8-item AFSS is unidimensional and has good psychometric qualities. The scale is sensitive to food scarcity cues and, therefore, can be used in experimental research. Moreover, its relatively narrow set of items makes it an exceptionally potent tool for use in online surveys, field settings, and lab studies. read more Taken together, the AFSS presents an alternative approach to food scarcity measurement in affluent societies and, consequently, can foster novel research on food waste, prosocial behaviors, and other similar topic areas.Over decades, the prevailing standard in drug discovery was the concept of designing highly selective compounds that act on individual drug targets. However, more recently, multi-target and combinatorial drug therapies have become an important treatment modality in complex diseases, including neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The development of such network-based approaches is facilitated by the significant advance in our understanding of the pathophysiological processes in these and other complex brain diseases and the adoption of modern computational approaches in drug discovery and repurposing. However, although drug combination therapy has become an effective means for the symptomatic treatment of many complex diseases, the holy grail of identifying clinically effective disease-modifying treatments for neurodegenerative and other brain diseases remains elusive. Thus, despite extensive research, there remains an urgent need for novel treatments that will modify the progression of the disease or prevent its development in patients at risk. Here we discuss recent approaches with a focus on multi-targeted drug combinations for prevention or modification of epilepsy. Over the last ~10 years, several novel promising multi-targeted therapeutic approaches have been identified in animal models. We envision that synergistic combinations of repurposed drugs as presented in this review will be demonstrated to prevent epilepsy in patients at risk within the next 5-10 years.Leishmaniasis is a neglected parasitic disease for which the conventional treatment can be considered inefficient and extremely aggressive, generating several and severe side effects. Therefore, the discovery of new drug candidates is important for the improvement in the quality of life of patients. Previously, we reported the promising results of isopentyl caffeate (ICaf) against Leishmania chagasi (agent of visceral leishmaniasis) and Leishmania amazonensis (agent of cutaneous leishmaniasis) promastigotes, displaying IC50 of 1.56 and 1.71 μM, respectively. Herein, we aimed to decipher the mechanisms of anti-Leishmania action of ICaf. Light and scanning electron microscopy assays showed relevant morphological changes in promastigotes when treated with ICaf, including rounding of the parasite body, shortening of the flagellum, blebs on the plasma membrane and cellular aggregation. The parasite mitochondrion was targeted by ICaf, resulting in a significant reduction in its metabolic activity and electric membrane potential followed by an increase in the production of reactive oxygen species, which culminated in the loss of plasma membrane integrity and parasite death. Relevantly, ICaf also had a potent anti-amastigote action. The IC50 values calculated for intracellular amastigotes of L. amazonensis were 3.27, 1.60 and 1.52 μM, while for L. chagasi the values were 2.48, 1.84 and 1.60 μM, respectively, after treating the infected macrophages with ICaf for 24, 48 and 72 h. ICaf was well tolerated by THP-1 macrophages, which gave rise to excellent selectivity indexes considering both Leishmania species. The current results suggest that ICaf may emerge as a chemotherapeutic alternative for the treatment of leishmaniasis.
Multimodal Analgesia (MMA) has shown promising results in postoperative outcomes across a broad spectrum of surgeries, including bariatric surgery. We compared the analgesic effect immediately after Laparoscopic Bariatric Surgery (LBS) of the combined effect of MMA and methadone against two techniques that were based mainly on the use of high-potency medium-acting opioids.
Two hundred seventy-one patients were retrospectively reviewed. The primary outcome was postoperative pain score>3/10 measured by the Verbal Numeric Scale (VNS) during the Postanesthetic Care Unit (PACU) stay. The three protocols of intraoperative analgesia were (P1) sufentanil at anesthetic induction followed by remifentanil infusion; (P2) sufentanil at induction followed by dexmedetomidine infusion; and (P3) remifentanil at induction followed by MMA including dexmedetomidine, magnesium, lidocaine, and methadone. Only P1 and P2 patients received morphine toward the end of surgery. Poisson regression was used to adjust confounding fa
Self-regulated professions such as medicine are characterized by professional commitment to the public they serve and require life-long development of expected skills. There is a paucity of data regarding quality of training during residency in anesthesiology. The objective of this study was to create an instrument to assess the anesthesiologists' perception regarding the quality of their training during medical residency.
An electronic questionnaire was sent to 120 anesthesiologists, assuming 15% response rate for worst case scenario, considering a number of 613 potential respondents. The answers to the questionnaire were submitted to psychometric evaluation through internal consistency analysis measured by the Cronbach's alpha coefficient, and factorial analysis by the principal components' method with varimax rotation method with Kaiser normalization. The level of Concordance (C) and Disaccord (D) of each item were compared byz tests (consensus if p<0.05). A question asking the respondents if they would recommend their training center to a relative or a friend was added to the questionnaire and considered as a secondary outcome.
