Lipid Changes During Endocrine Therapy in Breast Cancer Patients: The Results of a 5-Year Real-World Retrospective Analysis

BackgroundThe aim of this study was to investigate the status of serum lipids during endocrine therapy.MethodsWe retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy.ResultsFor premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p<0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p<0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p<0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years.ConclusionsTAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.

Excess Iodine Exposure Acutely Increases Salivary Iodide And Antimicrobial Hypoiodous Acid Concentrations In Humans

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, we measured the concentrations of these analytes in human saliva before and after iodine administration to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Salivary iodide, SCN-, HOI and OSCN- were measured using standard methodology. Salivary iodide and HOI levels significantly increased after iodinated contrast injection compared with baseline levels, whereas there was no significant change in salivary SCN- and OSCN- levels. The contrast dye iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. Excess iodine exposure in humans increases the salivary output of iodide, increasing salivary HOI concentrations with no effect on SCN-/OSCN- levels. This first of its kind study suggests that a sufficient but safe iodide supplementation may augment the generation of antimicrobial HOI by the salivary LPO system against airborne viral pathogens, including coronaviruses and influenza viruses, a possible inexpensive means of effectively curbing viral pandemics.

Testing the Efficacy of ‘Unlearning’, a Mindfulness and Compassion-Based Programme for Cultivating Nonviolence in Teenagers: A Randomised Controlled Trial

Background: Most programmes developed to reduce aggressive attitudes among teenagers are based on cultivating nonviolence, a construct that has been related to compassion and, more indirectly, mindfulness. This study aims at testing the efficacy of ‘Unlearning’, a mindfulness and compassion-based programme, for reducing aggressive attitudes in adolescents.Method: A sample of 164 students from three high schools in Zaragoza (Spain) participated in the study. They were randomly assigned to (1) ‘Unlearning’, or (2) relaxation programme. Three assessment points were established: baseline, post-treatment and a 4-month follow-up. The outcome variables were the subscales of the ‘Attitudes Toward Social Aggression Scale’. Mindfulness and compassion were assessed as secondary outcomes.Results: ‘Unlearning’ did not produce changes in the primary outcomes, but significant effects were observed post-treatment in self-compassion; and in the follow-up, in self-compassion and mindfulness. The control group did not experience any change post-treatment, but a significant effect in mindfulness was observed in the follow-up. The intergroup analyses indicated that ‘Unlearning’ improved self-compassion, both post-treatment (t = −2.48, p = 0.014) and after 4-months (t = −2.03, p = 0.044), although these results were not statistically significant after correcting for multiple comparisons.Conclusion: ‘Unlearning’ did not produce significant reductions in aggressive attitudes compared to the control group. The low baseline levels may have hindered the efficacy of the interventions. ‘Unlearning’ showed potential to improve self-compassion, which is related to nonviolence, and this may have positive implications for the adolescents. Future interventions should include teachers and families to enhance the effectiveness of the programmes.

The Effect of IL-35 on the Expression of Nasal Epithelial-Derived Proinflammatory Cytokines

Background. Airway epithelium plays an important role during the development of allergic rhinitis (AR), which is characterized by production of thymic stromal lymphopoietin (TSLP), interleukin 33 (IL-33), and interleukin 25 (IL-25). IL-35, mainly expressed by Treg cells, have negative regulation in Th2, Th17, and ILC2 inflammation. However, the effect of IL-35 on human nasal epithelial cells (HNECs) especially the secretion of nasal epithelial-derived proinflammatory cytokines as well as the possible mechanism is still unclear. Methods. HNECs were cultured and stimulated by various stimulators. The expression of IL-33, IL-25, TSLP, eotaxin-1, eotaxin-2, and eotaxin-3 from supernatant was measured using real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). AR mice were developed to verify the effect of IL-35 on nasal epithelial cells in vivo. Results. After Poly I:C stimulation, IL-35 inhibited the production of IL-25, and TSLP from HNECs increased significantly compared with baseline levels ( P < 0.05 ). After Dermatophagoides pteronyssinus or Aspergillus fumigatus stimulation, IL-35 inhibited the production of IL-25, IL-33, and TSLP from HNECs increased significantly compared with baseline levels ( P < 0.05 ). After Dermatophagoides pteronyssinus, IL-35 inhibited the production of eotaxin-1, eotaxin-2, and eotaxin-3 released from HNECs increased significantly compared with baseline levels ( P < 0.05 ). Similarly, IL-35-treated AR mice presented with decreased expression of IL-33, IL-25, TSLP, eotaxin-1, eotaxin-2, and eotaxin-3 in nasal lavage fluid. Conclusion. IL-35 suppressed both type 2 inflammation-inducing cytokines and eosinophil chemotactic factor from HNECs, suggesting the important role of IL-35 during the development of AR.

Outcomes Based on Plasma Biomarkers for the Phase 3 CELESTIAL Trial of Cabozantinib versus Placebo in Advanced Hepatocellular Carcinoma

<b><i>Introduction:</i></b> Cabozantinib, an inhibitor of MET, AXL, and VEGF receptors, significantly improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). In this exploratory analysis, outcomes were evaluated according to plasma biomarker levels. <b><i>Methods:</i></b> Baseline plasma levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, EPO, ANG2, IGF-1, VEGF-C, and c-KIT for 674/707 randomized patients; and Week 4 levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, and EPO for 614 patients. OS and PFS were analyzed by baseline levels as dichotomized or continuous variables and by on-treatment changes at Week 4 as continuous variables; biomarkers were considered potentially prognostic if <i>p</i> &#x3c; 0.05 and predictive if <i>p</i> &#x3c; 0.05 for the interaction between treatment and the biomarker. Multivariable analyses adjusting for clinical covariates were also performed. <b><i>Results:</i></b> In the placebo group, high levels of MET, HGF, GAS6, IL-8, and ANG2 and low levels of IGF-1 were associated with shorter OS in univariate and multivariable analyses; these associations were also observed for MET, IL-8, and ANG2 in the cabozantinib group. Hazard ratios for OS and PFS favored cabozantinib over the placebo at low and high baseline levels for all biomarkers. No baseline biomarkers were predictive of a treatment benefit. Cabozantinib promoted pharmacodynamic changes in several biomarkers, including increases in VEGF-A, PlGF, AXL, and GAS6 levels and decreases in VEGFR2 and HGF levels; these changes were not associated with OS or PFS. <b><i>Conclusion:</i></b> Cabozantinib improved OS and PFS versus placebo at high and low baseline concentrations for all biomarkers analyzed. Low baseline levels of MET, HGF, GAS6, IL-8, and ANG2 and high levels of IGF-1 were identified as potential favorable prognostic biomarkers for survival in previously treated advanced HCC. Although cabozantinib promoted pharmacodynamic changes in several biomarkers, these changes were not associated with survival.

Two or four injections of platelet-rich plasma for osteoarthritic knee did not change synovial biomarkers but similarly improved clinical outcomes

We compared two and four intra-articular injections of platelet-rich plasma (PRP) in terms of changes of synovial cytokines and clinical outcomes. One hundred twenty-five patients having knee osteoarthritis (OA) underwent PRP injections at a 6-week interval. Before each PRP injection, synovial fluid aspiration was collected for investigation. Patients were divided into two or four intra-articular PRP injections (group A and B, respectively). Changes in synovial biomarkers were compared with the baseline levels of both groups, and clinical outcomes were evaluated until one year. Ninety-four patients who had completed synovial fluid collection were included for final evaluation, 51 in group A and 43 in group B. There were no differences in mean age, gender, body mass index (BMI), and radiographic OA grading. The average platelet count and white blood cell count in PRP were 430,000/µL and 200/ µL, respectively. There were no changes of synovial inflammatory cytokines (IL-1β, IL-6, IA-17A, and TNF-alpha), anti-inflammatory cytokines (IL-4, IL-10, IL-13, and IL-1RA), and growth factors (TGF-B1, VEGF, PDGF-AA, and PDGF-BB) between baseline levels and six weeks in group A, and 18 weeks in group B. Both groups had significantly improved clinical outcomes from six weeks including visual analog scale (VAS), patient-reported outcome measures [PROMs; Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form-12 (SF-12)], with a significant delayed improvement of performance-based measures [PBMs; time up and go (TUG), 5-time sit to stand test (5 × SST), and 3-min walk test (3-min WT)]. In conclusion, two- or four-PRP intra-articular injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until 1 year.

Changes in Physical Fitness of Older People During the COVID-19 Pandemic in Germany: Objective Training Data

The purpose of this study was to analyze objective training data on changes in leg muscle training before and after the COVID-19 lockdown during spring 2020 in Germany. Overall, the training data of 4435 individuals in the age group (AG) 45-64 years (55±5 years, 66% ♀) and of 2853 in the AG 65-95 years (72±6 years, 54% ♀) were exported from chip-controlled exercise circuits. Training weight and number of repetitions performed on the leg extensor were used to calculate a leg score (LS), considering the last three training sessions before the lockdown (baseline) and the first ten individual sessions as well as the averaged sessions for August, September and October after individual training resumption. Based on the baseline LS, three training intensity groups (TG_low, medium, high) were defined, and analyzed for differences (ANOVA). The LS in TG_low remained stable after the lockdown, but increased compared to baseline in both AGs after the first ten sessions (p&lt;0.05). In TG_medium, LS was reduced at the first post training session (p&lt;0.05) and returned to baseline levels at training session eight in the younger and session two in the older adults. In both AGs, LS was reduced in the TG_high (p&lt;0.001), and did not reach baseline levels by October. Hence, the LS of TG_high was identified as being particularly affected by the training interruption, irrespective of age. More individually tailored training recommendations should be made for these individuals to be able to regain their initial training levels and avoid long-term adverse health effects.

Optimism Is Prospectively Associated With Resilience During the COVID-19 Pandemic

Emerging research has identified how protective factors—like optimism—are associated with resilience to stress during the COVID-19 pandemic. However, the majority of research is cross-sectional, which creates ambiguity around the causal direction because these very protective factors might have also changed due to the pandemic. In the current study, we used longitudinal data from the Health and Retirement Study (N = 921; Mage = 64.54, SD = 10.71; 59.6% female; 57.5% White) to examine how optimism measured in 2016 predicted adjustment during the pandemic (in 2020). Higher baseline levels of optimism were subsequently associated with less worrying and stress resulting from changes in social contacts (βs &gt; |.10|), less loneliness and not feeling overwhelmed (βs &gt; |.16|), and greater COVID-related resilience and benefit-finding (β = .21). The findings will be discussed in the context of mechanisms that facilitate the protective functions of optimism and other psychological characteristics.

Estimation of baseline levels of bacterial community tolerance to Cr, Ni, Pb, and Zn in unpolluted soils, a background for PICT (pollution-induced community tolerance) determination

The PICT method (pollution-induced community tolerance) can be used to assess whether changes in soil microbial response are due to heavy metal toxicity or not. Microbial community tolerance baseline levels can, however, also change due to variations in soil physicochemical properties. Thirty soil samples (0–20 cm), with geochemical baseline concentrations (GBCs) of heavy metals and from five different parent materials (granite, limestone, schist, amphibolite, and serpentine), were used to estimate baseline levels of bacterial community tolerance to Cr, Ni, Pb, and Zn using the leucine incorporation method. General equations (n = 30) were determined by multiple linear regression using general soil properties and parent material as binary variables, explaining 38% of the variance in log IC50 (concentration that inhibits 50% of bacterial growth) values for Zn, with 36% for Pb, 44% for Cr, and 68% for Ni. The use of individual equations for each parent material increased the explained variance for all heavy metals, but the presence of a low number of samples (n = 6) lead to low robustness. Generally, clay content and dissolved organic C (DOC) were the main variables explaining bacterial community tolerance for the tested heavy metals. Our results suggest that these equations may permit applying the PICT method with Zn and Pb when there are no reference soils, while more data are needed before using this concept for Ni and Cr.