Ramoskofod6022

Mass spectrometry imaging (MSI) has seen remarkable development in recent years. The possibility of getting quantitative or semiquantitative data, while maintaining the spatial component in the tissues has opened up unique study possibilities. Now with a spatial window of few tens of microns, we can characterize the events occurring in tissue subcompartments in physiological and pathological conditions. For example, in oncology-especially in preclinical models-we can quantitatively measure drug distribution within tumors, correlating it with pharmacological treatments intended to modify it. We can also study the local effects of the drug in the tissue, and their effects in relation to histology. This review focuses on the main results in the field of drug MSI in clinical pharmacology, looking at the literature on the distribution of drugs in human tissues, and also the first preclinical evidence of drug intratissue effects. The main instrumental techniques are discussed, looking at the different instrumentation, sample preparation protocols, and raw data management employed to obtain the sensitivity required for these studies. Finally, we review the applications that describe in situ metabolic events and pathways induced by the drug, in animal models, showing that MSI makes it possible to study effects that go beyond the simple concentration of the drug, maintaining the space dimension. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.Tendinopathy is a common musculoskeletal disorder characterized by chronic low-grade inflammation and tissue degeneration. Tendons have poor innate healing ability and there is currently no cure for tendinopathy. Studies elucidating mechanisms underlying the pathogenesis of tendinopathy and mechanisms mediating the genesis of tendons during development have provided novel targets and strategies to enhance tendon healing and repair. This review summarizes the current understanding and treatments for tendinopathy. The review also highlights recent advances in gene therapy, the potential of noncoding RNAs, such as microRNAs, and exosomes, which are nanometer-sized extracellular vesicles secreted from cells, for the treatment of tendinopathy.Oxidation of protein methionines to methionine-sulfoxides (MetOx) is associated with several age-related diseases. In healthy cells, MetOx is reduced to methionine by two families of conserved methionine sulfoxide reductase enzymes, MSRA and MSRB that specifically target the S - or R -diastereoisomers of methionine-sulfoxides, respectively. To directly interrogate MSRA and MSRB functions in cellular settings, we developed an NMR-based biosensor that we call CarMetOx to simultaneously measure both enzyme activities in single reaction setups. We demonstrate the suitability of our strategy to delineate MSR functions in complex biological environments, including cell lysates and live zebrafish embryos. Thereby, we establish differences in substrate specificities between prokaryotic and eukaryotic MSRs and introduce CarMetOx as a highly sensitive tool for studying therapeutic targets of oxidative stress-related human diseases and redox regulated signaling pathways.Phosphodiesterase-5 inhibitors are the first-line therapy for erectile dysfunction (ED) after radical prostatectomy (RP). This single-centre open-label uncontrolled study evaluated the efficacy and safety of the new sildenafil orodispersible film (ODF) in ED treatment after RP. Sildenafil 100 mg ODF was administered twice a week for 3 months to patients under 75 years of age, with a Framingham cardiovascular risk score less then 20% and a pre-operative International Index of Erectile Function (IIEF)-5 score ≥ 17, who had undergone open RP between 2016 and 2018. Erectile function was assessed pre-operatively, post-operatively and after treatment through the IIEF-5 score, the Sexual Encounter Profile Question (SEP-Q) 2 and SEP-Q3; adverse events (AE) were also investigated after 3 months. A total of 65 patients with a median (25th-75th percentile) post-operative IIEF-5 score of 8 (7-9) were treated. Nine (13.8%) patients reported AE of mild/moderate grade and discontinued treatment. A significant IIEF-5 score median (25th-75th percentile) increase of 10 (0-12) was found after treatment in the other 56 patients (p less then .001). Sildenafil 100 mg ODF was effective in ED after RP in terms of improved IIEF-5 score and improved SEP-Q2 and SEP-Q3 in 67.9% of patients. It could represent a valid alternative for those patients with low compliance to tablet intake.The present study is aimed at the evaluation of the phytochemical profile and the biochemical properties of methanolic extracts obtained from different parts of Rumex algeriensis and Rumex tunetanus , two relict species limited to the North Africa. Phytochemical analyses of these extracts were performed using standard colorimetric procedures, HPLC-DAD, and HPLC-DAD-ESI/MS, and their antioxidant/free radical scavenging capability was estimated through several in vitro cell-free assays. Moreover, the anti-inflammatory potential of these extracts was demonstrated in an in vitro model of acute intestinal inflammation using differentiated Caco-2 cells. The results show that all the extracts appeared endowed with excellent antioxidant/free radical scavenging properties. In particular, the extracts from both R. algeriensis and R. tunetanus flowers, and that from R. algeriensis stems are characterized by a remarkable SOD-like and NO-scavenging activity, as well as by the capability to protect albumin against HClO-induced degradation. Furthermore, the extracts from flowers of both Rumex species, as wells as R. algeriensis stems, showed an anti-inflammatory effect in intestinal epithelial cells, as demonstrated by the inhibition of TNF-α-induced gene expression of IL-6 and IL-8. In conclusion, R. algeriensis and R. tunetanus have shown to be potential sources of bioactive products to be used in the prevention and treatment of pathologies related to oxidative stress and inflammation.Aims The aims of the present study were a) to investigate the current state of postpartum glucose screening in rural China; and b) to explore the factors influencing postpartum blood glucose screening among women with prior GDM based on Andersen's behavioural model of health service use. Design A multisite, cross-sectional study design, conducted from November 2017 to January 2018. Methods A total of 465 women with prior GDM were included from two county-level hospitals in rural China. The potential influencing factors for postpartum blood glucose screening based on Andersen's behavioural model, including predisposing, enabling, and need factors, were collected by self-reported questionnaires. Chi-square tests and logistic regression were used to explore the influence of these factors on whether screening of blood glucose level after delivery occurred. Results The mean age of the women was 31.92 years old (SD 5.16) and the mean time after delivery was 16.73 months (SD 15.07). The postpartum glucose screening proportion was 32.7%. Women who did not have a full-time job (p= .011) (predisposing factor), had not received any treatment for GDM (p= .002), and were not informed about screening plans for diabetes by health professionals (p .05). Conclusions In rural China, most women with prior GDM were not screened for T2DM after delivery. The women with prior GDM who did not have a full-time job or had not received any prior treatment for GDM should be the target population for health education on postpartum glucose screening. Impact There is a need for data on postpartum blood glucose testing rates among rural women. Future interventions aimed at increasing postpartum blood glucose screening are needed.During the COVID-19 pandemic, the world witnessed varied responses from educational institutions to the lockdown. Within the next few years, we will see the consequences of these responses. Despite the disruption at this critical time, candidates in their final fellowship training year still need to be certified and it is arguable that they should be certified faster than ever after passing the written component.Objectives The extent to which dentists are happy with their profession and their life has not been well studied. The present study aimed to explore the level of happiness, satisfaction with life and psychological well-being among a sample of dental professionals from 21 countries. Materials and methods The sample comprised 2,200 dentists from 21 countries. Three scales - Subjective Happiness Scale (SHS), Satisfaction With Life Scale (SWLS), and Affect Balance Scale (ABS) - were used to measure the subjective responses. Data related to demographic and social characteristics were recorded. Mann-Whitney and Kruskal-Wallis tests were used as appropriate. Scales were correlated, and multiple linear regression analyses were employed to identify the independent determinants of SHS, SWLS and ABS. Data were analysed using the SPSS software program; a value of P less then 0.05 was considered significant. Results The overall mean scores of SHS, SWLS and ABS were 18.53 ± 5.06, 23.06 ± 6.25 and 1.26 ± 2.40, respectively, with significant differences found across countries dentists working in Croatia, Peru and Serbia recorded the highest scores, unlike dentists practicing in Yemen, Syria, and Iraq, who recorded the lowest scores. There were significant, moderately positive correlations between the various scales SHS and SWLS r = 0.535, P less then 0.001; SHS and ABS r = 0.58, P less then 0.001; and SWLS and ABS r = 0.533, P less then 0.001. Country of practice, age, qualification and monthly income were the significant independent predictors of SHS, SWLS and ABS. Conclusion Country of residence and social characteristics were associated with dentists' responses regarding their feelings and subjective well-being.Background Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. Methods We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. Results Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR] 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR 2.15; P = .0222), ISUP grade group (GG) 5 (HR 2.04; P = .0186) and ≥3 bone metastases (HR 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P less then .0001). Conclusion Not only the number of bone metastases, but also non-regional LN metastases predict OS in patients with de novo oligometastatic PCa.