Objective
Cognitive complaints are more frequent in women with breast cancer (BC) than in healthy controls and can be present before any treatment. Findings regarding contributive factors remain ...inconsistent. This study aimed to identify different groups of patients with cognitive complaints at BC diagnosis and to determine whether these different groups were associated with demographic, medical, or psychological characteristics.
Methods
Cognitive complaints were assessed in a subset of 264 women from the French multicenter prospective CANTO cohort, at baseline before any treatment. Clustering analyzes were performed using the six‐cognitive dimension Costa's scoring of the FACT‐Cog V3. Univariable analyses were used to study how cognitive function (standardized neuropsychological tests, ICCTF), anxiety, depression, fatigue, and quality of life (HADS, FA12, QLQ‐C30) were associated with specific cognitive complaints groups.
Results
Results included 263 women (54±11 years), newly diagnosed with BC (69% stages I–III). Four distinct groups emerged, ranged from “no complaints” (22.8%), “low complaints” (55.1), “mixed complaints” (14.5%), to “consistent complaints” (7.6%). No significant differences were found in terms of demographic and medical factors between the four groups. However, the groups with higher proportions of patients with complaints were found to have more impairment in executive function, higher scores of anxiety, depressive symptoms, and fatigue, and lower quality of life, than the groups with lower proportions of cognitive complaints.
Conclusion
Using complete cognitive assessment prior to BC treatment, we identified four distinct cognitive complaints groups with specific characteristics. This work provides valuable clinical basis to further investigations for a better understanding of cognitive complaints and their associates.
Mitochondria have been in the focus of oxidative stress and aging research for decades due to their permanent production of ROS during the oxidative phosphorylation. The hypothesis exists that ...mitochondria are involved in the formation of lipofuscin, an autofluorescent protein aggregate that accumulates progressively over time in lysosomes of post-mitotic and senescent cells. To investigate the influence and involvement of mitochondria in lipofuscinogenesis, we analyzed lipofuscin amounts as well as the mitochondrial function in young and senescent cells. In addition we used an aging model and Lon protease deficient HeLa cells to investigate the influence of mitochondrial degradation processes on lipofuscin formation.
We were able to show that mitophagy is impaired in senescent cells resulting in an increased mitochondrial mass and superoxide formation. In addition, the inhibition of mitochondrial fission leads to increased lipofuscin formation.
Moreover, we observed that Lon protease downregulation is linked to a higher lipofuscinogenesis whereas the application of the mitochondrial-targeted antioxidant mitoTEMPO is able to prevent the accumulation of this protein aggregate.
To evaluate the efficacy of trastuzumab in patients with node-positive breast cancer treated with surgery, adjuvant chemotherapy, radiotherapy, and hormone therapy if applicable.
Three thousand ten ...patients with operable node-positive breast cancer were randomly assigned to receive adjuvant anthracycline-based chemotherapy with or without docetaxel. Patients who presented human epidermal growth factor receptor 2 (HER2) -overexpressing tumors were secondary randomly assigned to either a sequential regimen of trastuzumab (6 mg/kg every 3 weeks) for 1 year or observation. The primary end point was disease-free survival (DFS).
Overall 528 patients were randomly assigned between trastuzumab (n = 260) and observation (n = 268) arm. Of the 234 patients (90%) who received at least one administration of trastuzumab, 196 (84%) received at least 6 months of treatment, and 41 (18%) discontinued treatment due to cardiac events (any grade). At the date of analysis (October 2007), 129 DFS events were recorded. Random assignment to the trastuzumab arm was associated with a nonsignificant 14% reduction in the risk of relapse (hazard ratio, 0.86; 95% CI, 0.61 to 1.22; P = .41, log-rank stratified on pathologic node involvement). Three-year DFS rates were 78% (95% CI, 72.3 to 82.5) and 81% (95% CI, 75.3 to 85.4) in the observation and trastuzumab arms, respectively.
After a 47-month median follow-up, 1 year of trastuzumab given sequentially after adjuvant chemotherapy was not associated with a statistically significant decrease in the risk of relapse.
•Pear flowers are less visited by bees than apple flowers.•Bees mainly visit pear flowers for pollen, and apple flowers for nectar.•Nectar sugar concentration is lower in pear than apple ...flowers.•Polypeptide, amino-acid, and phytosterol concentrations are high in pear pollen.•Chemical quality of floral resources appears to explain pollinator behavior.
Pear and apple are among the main fruit crops worldwide. These species can be planted in mixed orchards, and they both depend on insect pollination for fruit set. As pollinating insects are attracted by the floral resources, we investigated nectar and pollen production and chemical composition in four pear (‘Concorde’, ‘Conférence’, ‘Doyenné du Comice’, ‘Triomphe de Vienne’) and five apple (‘Braeburn’, ‘Golden Reinders’, ‘Jonagored’, ‘Pinova’, ‘Wellant’) cultivars commonly grown in Belgium. We also investigated whether insect flower visitation rate and pollination efficiency are linked to floral resource quantity and quality. The pear cultivars flowered one week before the apple cultivars in early spring, and their flowers were about six times less visited by insects. The visitors foraged more on the pollen of the pear trees and the nectar of the apple trees. Pear flowers produced higher volumes of nectar than apple flowers (1.3–3.2μl vs. 0.4-0.6μl), but with lower sugar concentration (9.6%-10.8% vs. 28.3%-36.4%). Pear flowers also produced fewer pollen grains per anther than apple flowers (2425–4937 vs. 3284–7919), but these had higher polypeptide (346–362μg/mg vs. 216–303μg/mg), amino-acid (40–77μg/mg vs. 12–18μg/mg) and phytosterol (21–47μg/mg vs. 15–43μg/mg) concentrations. The foraging behavior of the insects is thus better explained by nectar and pollen quality rather than quantity. Despite the differences in flower visitation rates, pollination of both species resulted in valuable fruit production.
The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in ...macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.
In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated ...benefits.
In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization.
Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval CI, 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported.
In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).
A common feature of glasses is the "boson peak", observed as an excess in the heat capacity over the crystal or as an additional peak in the terahertz vibrational spectrum. The microscopic origins of ...this peak are not well understood; the emergence of locally ordered structures has been put forward as a possible candidate. Here, we show that depolarised Raman scattering in liquids consisting of highly symmetric molecules can be used to isolate the boson peak, allowing its detailed observation from the liquid into the glass. The boson peak in the vibrational spectrum matches the excess heat capacity. As the boson peak intensifies on cooling, wide-angle x-ray scattering shows the simultaneous appearance of a pre-peak due to molecular clusters consisting of circa 20 molecules. Atomistic molecular dynamics simulations indicate that these are caused by over-coordinated molecules. These findings represent an essential step toward our understanding of the physics of vitrification.
The use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its ...effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa.
We conducted a matched case-control study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were confirmed by means of a rapid test, and controls were selected among neighbors of the same age and sex as the case patients. The odds of vaccination were compared between case patients and controls in bivariate and adjusted conditional logistic-regression models. Vaccine effectiveness was calculated as (1-odds ratio)×100.
Between June 8 and October 19, 2012, we enrolled 40 case patients and 160 controls in the study for the primary analysis. After adjustment for potentially confounding variables, vaccination with two complete doses was associated with significant protection against cholera (effectiveness, 86.6%; 95% confidence interval, 56.7 to 95.8; P=0.001).
In this study, Shanchol was effective when used in response to a cholera outbreak in Guinea. This study provides evidence supporting the addition of vaccination as part of the response to an outbreak. It also supports the ongoing efforts to establish a cholera vaccine stockpile for emergency use, which would enhance outbreak prevention and control strategies. (Funded by Médecins sans Frontières.).
Foot orthotics (FOs) are frequently prescribed to provide comfortable walking for patients. Finite element (FE) simulation and 3D printing pave the way to analyse, optimize and fabricate functionally ...graded lattice FOs where the local stiffness can vary to meet the therapeutic needs of each individual patient. Explicit FE modelling of lattice FOs with converged 3D solid elements is computationally prohibitive. This paper presents a more computationally efficient FE model of cellular FOs.
The presented FE model features shell elements whose mechanical properties were computed from the numerical homogenization technique. To verify the results, the predictions of the homogenized models were compared to the explicit model's predictions when the FO was under a static pressure distribution of a foot. To validate the results, the predictions were also compared with experimental measurements when the FO was under a vertical displacement at the medial longitudinal arch.
The verification procedure showed that the homogenized model was 46 times faster than the explicit model, while their relative difference was less than 8% to predict the local minimum of out-of-plane displacement. The validation procedure showed that both models predicted the same contact force with a relative difference of less than 1%. The predicted force-displacement curves were also within a 90% confidence interval of the experimental measurements having a relative difference smaller than 10%. In this case, using the homogenized model reduced the computational time from 22 h to 22 min.
The presented homogenized model can be therefore employed to speed up the FE simulation to predict the deformations of the cellular FOs.
•We introduced a computationally efficient FE model of a honeycomb lattice foot orthotic by numerical homogenization.•The homogenized model's prediction is verified by the explicit model's prediction and validated by the experimental measurements.•The homogenized model predicts the same displacement field as the explicit model, but it is 46 times faster.•In a contact simulation, the homogenized model predicts the force-displacement curve 60 times faster than the explicit model. The relative difference between their predictions is less than 1.0%.•Both models predict a contact force close to the experimental results with a relative difference smaller than 10%.
We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall ...NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%).
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