Differential associations of proinflammatory and anti-inflammatory cytokines with depression severity from noncancer status to breast cancer course and subsequent chemotherapy.

BACKGROUND: In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment. METHODS: A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1ß, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire. RESULTS: After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy. CONCLUSIONS: Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.

Hybrid electron microscopy-FRET imaging localizes the dynamical C-terminus of Tfg2 in RNA polymerase II-TFIIF with nanometer precision.

TFIIF-a general transcription factor comprising two conserved subunits can associate with RNA polymerase II (RNAPII) tightly to regulate the synthesis of messenger RNA in eukaryotes. Herein, a hybrid method that combines electron microscopy (EM) and Förster resonance energy transfer (FRET) is described and used to localize the C-terminus of the second TFIIF subunit (Tfg2) in the architecture of RNAPII-TFIIF. In the first stage, a poly-histidine tag appended to the Tfg2 C-terminus was labeled with nickel-NTA nanogold and a seven-step single particle EM protocol was devised to obtain the region accessible by the nanogold in 3D, suggesting the Tfg2 C-terminus is proximal to the clamp of RNAPII. Next, the C-termini of the Rpb2 and the Rpb4 subunits of RNAPII, adjacent to the clamp, were selected for placing FRET satellites to enable the nano-positioning (NP) analysis, by which the localization precision was improved such that the Tfg2 C-terminus was found to dwell on the clamp ridge but could move to the clamp top during transcription. Because the tag receptive to the EM or FRET probes can be readily introduced to any protein subunit, this hybrid approach is generally applicable to complement cryo-EM study of many protein complexes to nanometer precision.

Cognitive function and breast cancer molecular subtype before and after chemotherapy.

Chemotherapy-related cognitive impairment has been reported in patients with breast cancer and received growing attention due to increased survival rate. However, cognitive outcome according to pathological tumor features, especially human epidermal growth factor receptor (HER2) status, has not been clearly elucidated. Despite its potential link with cognitive status through neuroinflammatory response, existing research is sparse and limited to cross-sectional studies. In this observational cohort study, 52 breast cancer patients received a series of neuropsychological examinations before and after chemotherapy. Patients' performances were compared with normative data, and analyzed with Reliable Change Indices and mixed-model analysis of covariance. Results showed that there was a higher percentage of HER2+ patients than HER2- patients who showed defective attention and processing speed before chemotherapy, and that there were more patients with HER2+ status showing cognitive decline on tests of attention and executive functions following chemotherapy. Group-wise analyses confirmed the foregoing pattern and further revealed that patients with HER2+ status also tended to deteriorate more in verbal memory after chemotherapy. These findings indicate that HER2 overexpression may serve as prognostic factors that help explain the heterogeneous cognitive outcome in breast cancer survivors. Further studies are needed to replicate this finding and delineate the underlying mechanisms.

Sleep Quality and Related Factors in Patients with Breast Cancer: A Cross-Sectional Study in Taiwan.

BACKGROUND: Sleep disturbances are common and symptomatic burden in patients with breast cancer, but they are poorly documented and managed in routine clinical practice. This descriptive and cross-sectional study evaluated factors associated with post-treatment sleep disturbances in patients with breast cancer. PATIENTS AND METHODS: Patients with breast cancer who underwent standard treatment were enrolled and surveyed for their basic demographic data and precancerous and cancer treatment-related factors; they were also administered self-report questionnaires including the Family Adaptation, Partnership, Growth, Affection, Resolve questionnaire; Impact of Event Scale; Center for Epidemiologic Studies Depression Scale; and Maudsley Personality Inventory. Their sleep disturbances were evaluated using the Pittsburgh sleep quality index (PSQI). Independent sample t test and chi-square tests were used to compare the variables between patients with or without sleep disturbance, and multivariate logistic regression analyses were conducted to detect the independent factors. RESULTS: In total, 448 patients, including 145 with PSQI ≤ 5 and 303 with PSQI > 5, completed the investigation. Multiple logistic regression analysis revealed that significantly more patients with sleep disturbances demonstrated psychological distress, severe pain, depression, and impact of stress events than patients without sleep disturbances (adjusted odds ratios [95% confidence intervals]: 2.83 [1.135-7.067], P = 0.026; 1.14 [1.023-1.280], P = 0.018; 1.08 [1.036-1.133], P < 0.001; and 1.03 [1.002-1.051], P = 0.037, respectively). CONCLUSION: Patients with breast cancer showed 67.6% prevalence of sleep disturbances after treatment. The patients with sleep disturbances were more likely to have previously experienced psychological disturbances, severe pain, depression within 5 years after diagnosis. After diagnosis for more than 5 years, higher distress caused by traumatic events still associated with sleep disturbances.

Circulating cytokines as predictors of depression in patients with breast cancer.

Depression is a common comorbid disorder associated with breast cancer, and it can have considerable physical and psychological impacts. Circulating cytokines have been proposed as a potential tool to predict depression in various diseases; however, limited studies have specifically examined it in breast cancer. In this study, we examined and compared the prediction ability of various circulating cytokines for depression in patients with breast cancer. Eighty-three patients with a new diagnosis of breast cancer not receiving chemotherapy were recruited; among them, 15 patients had depression and 68 did not have depression. Depression was evaluated using the Patient Health Questionnaire 9 (PHQ-9). Cytokine levels in the serum were measured using an immunology multiplex assay. Two types of cytokines were assayed: (1) proinflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-6, IL-12, IL-17A, interferon [IFN]γ, and tumor necrosis factor [TNF]α) and (2) anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). Receiver operating characteristic (ROC) analysis was performed to calculate the area under the curves (AUCs), sensitivities, and specificities of circulating cytokines for predicting depression. As a result, IL-2 (AUC = 0.78) and IL-5 (AUC = 0.76) demonstrated good predictability for depression, even after controlling for the covariates (i.e. age, education, stage of cancer, surgery, radiation therapy, and hormone therapy). The optimal cut-off value of IL-2 for predicting depression was 1.06 pg/mL with a sensitivity of 86.7% and a specificity of 52.9%; this cytokine also had the best prediction ability in this study. Owing to the prediction ability and practical feasibility of circulating cytokines, they may be used as a valid laboratory diagnostic tool for depression in breast cancer.

Subjective and objective cognitive functioning among patients with breast cancer: effects of chemotherapy and mood symptoms.

BACKGROUND: Previous findings regarding declines in cognitive functioning among patients with breast cancer (BC) before and after chemotherapy have been inconsistent. The present study explored the effect of BC and cancer-related chemotherapies on cognitive functioning. METHODS: A cross-sectional design was adopted to compare BC patients before their chemotherapy treatment, BC patients 3 ~ 9 months after the completion of chemotherapy, and noncancer controls. Evaluations of cognitive functioning included subjective and objective dimensions, with focus on memory, executive functioning, attention, and language. ANCOVA and Pearson's correlation analysis were used to examine the relationship among cancer, chemotherapy, cognitive performance, and psychological distress. RESULTS: After adjustment for intelligence quotient, anxiety, and depression, we found significant differences in the Semantic Association of Verbal Fluency between post-chemotherapy (C/T) patients and noncancer controls. Specifically, post-C/T patients scored lower than controls (p = 0.03, η2 = 0.07). No significant differences were found in other objective cognitive measures. However, both subjective and objective cognitive scores were significantly associated with depression, anxiety, and fatigue. In BC patients, levels of anxiety were positively correlated with measures of executive function. Among pre-C/T patients, self-perceived interference by fatigue was positively associated with better performances in some of the objective cognitive measures. CONCLUSION: Our findings suggest cognitive impairments in the domain of executive functioning among patients with BC who received chemotherapy. Providing relevant suggestions or strategies of managements for these negative consequences may help increase the long-term quality of life of patients with BC.

[Treatment of femoral periprosthetic fracture of Vancouver type B1 and C with bridge combined internal fixation system].

OBJECTIVE: To evaluate the clinical effect of bridge combined internal fixation system in the treatment of periprosthesis fracture of femur after hip replacement. METHODS: From October 2016 to June 2018, 5 patients of periprosthesis fractures of femur classified type B1 and type C in Vancouver were treated by open reduction and bridging combined with internal fixation, including 2 males and 3 females, with ages of 68, 70, 74, 75, 79 years;type B1 fractures in 4 and type C fractures in 1. Causes of injury:1 case of traffic injury, 4 cases of fall. After the operation, the patients were followed up for complications and fracture healing time by clinical and imaging examination, and Parker activity score was performed. RESULTS: The wounds of 5 patients healed without infection. One case of DVT was confirmed by venography. Five patients were followed up, and the durations were 2, 8, 9, 10, 15 months. One patient died of myocardial infarction 2 months after operation. The average healing time was 12.5 weeks. No loss of reduction or failure of internal fixation was found. Two patients could walk without protection and 1 patient needed to rely on single crutch. One case of periprosthetic fracture had to walk with a single crutch before operation and move indoors with two crutches after operation. The average Parker activity score was 51.8% before operation. CONCLUSION: The bridge combined internal fixation system can be used to fix the fracture after hip replacement with stable femoral prosthesis.

Correlations And Correlates Of Post-Traumatic Growth And Post-Traumatic Stress Symptoms In Patients With Breast Cancer.

PURPOSE: Although post-traumatic growth (PTG) and post-traumatic stress symptoms (PTSS) might develop and coexist after a major trauma, few studies have simultaneously examined them in patients with breast cancer. This study investigated the correlation between PTG and PTSS and their differential correlates in patients with breast cancer. PATIENTS AND METHODS: Overall, 145 patients with breast cancer were recruited. PTG and PTSS were assessed using the PTG inventory and the Chinese version of startle, physiological arousal, anger, and numbness, respectively. We investigated the effects of demographics, chemotherapy, depression, family support, alexithymia, and anxiety symptoms on PTG and PTSS. Multivariate linear regression analyses were performed to select the independent correlates of PTSS and PTG. RESULT: An association was observed between PTG and PTSS (r = 0.21). Based on multiple regression models, the common correlate of PTG (ß = 0.271) and PTSS (ß = 0.212) was anxiety symptoms. Differential independent correlates were years of education (ß = 0.272), receiving chemotherapy (ß = 0.248), and family support (ß = 0.259) for PTG, and chronic pain (ß = 0.316) and poor cognition (ß = -0.350) for PTSS. CONCLUSION: Differential correlates were observed for PTG and PTSS in patients with breast cancer. Possible mechanisms and relationships between PTG and PTSS were discussed.

Zernike phase plate cryoelectron microscopy facilitates single particle analysis of unstained asymmetric protein complexes.

Single particle reconstruction from cryoelectron microscopy images, though emerging as a powerful means in structural biology, is faced with challenges as applied to asymmetric proteins smaller than megadaltons due to low contrast. Zernike phase plate can improve the contrast by restoring the microscope contrast transfer function. Here, by exploiting simulated Zernike and conventional defocused cryoelectron microscope images with noise characteristics comparable to those of experimental data, we quantified the efficiencies of the steps in single particle analysis of ice-embedded RNA polymerase II (500 kDa), transferrin receptor complex (290 kDa), and T7 RNA polymerase lysozyme (100 kDa). Our results show Zernike phase plate imaging is more effective as to particle identification and also sorting of orientations, conformations, and compositions. Moreover, our analysis on image alignment indicates that Zernike phase plate can, in principle, reduce the number of particles required to attain near atomic resolution by 10-100 fold for proteins between 100 kDa and 500 kDa.