Prognostic and Clinical Significance of PD-L1, EGFR and Androgen Receptor (AR) Expression in Triple-Negative Breast Cancer (TNBC) Patients.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a 'high risk' profile of TNBC.

Elbow Joint Stiffness Functional Scales Based on Hill's Muscle Model and Genetic Optimization.

The ultimate goal of rehabilitation engineering is to provide objective assessment tools for the level of injury and/or the degree of neurorehabilitation recovery based on a combination of different sensing technologies that enable the monitoring of relevant measurable variables, as well as the assessment of non-measurable variables (such as muscle effort/force and joint mechanical stiffness). This paper aims to present a feasibility study for a general assessment methodology for subject-specific non-measurable elbow model parameter prediction and elbow joint stiffness estimation. Ten participants without sensorimotor disorders performed a modified "Reach and retrieve" task of the Wolf Motor Function Test while electromyography (EMG) data of an antagonistic muscle pair (the triceps brachii long head and biceps brachii long head muscle) and elbow angle were simultaneously acquired. A complete list of the Hill's muscle model and passive joint structure model parameters was generated using a genetic algorithm (GA) on the acquired training dataset with a maximum deviation of 6.1% of the full elbow angle range values during the modified task 8 of the Wolf Motor Function Test, and it was also verified using two experimental test scenarios (a task tempo variation scenario and a load variation scenario with a maximum deviation of 8.1%). The recursive least square (RLS) algorithm was used to estimate elbow joint stiffness (Stiffness) based on the estimated joint torque and the estimated elbow angle. Finally, novel Stiffness scales (general patterns) for upper limb functional assessment in the two performed test scenarios were proposed. The stiffness scales showed an exponentially increasing trend with increasing movement tempo, as well as with increasing weights. The obtained general Stiffness patterns from the group of participants without sensorimotor disorders could significantly contribute to the further monitoring of motor recovery in patients with sensorimotor disorders.

Patients' Fears and Perceptions Associated with Anesthesia.

Background and Objectives: It has been suggested that intense feelings of fear/anxiety and significant patient concerns may affect the perioperative course. Those findings emphasize the importance of surgical patients' preoperative feelings. Still, current knowledge in this area is based on a limited number of studies. Thus, we think that there is a need to further explore patients' preoperative fears, better characterize risk factors and reasons for their occurrence, and evaluate patients' perspectives associated with anesthesia. Materials and Methods: A total of 385 patients undergoing vascular surgery were preoperatively interviewed using a questionnaire that included demographics and questions related to patients' fears and perceptions of anesthesia. Statistical analyses included descriptive statistics, Pearson's χ2 and McNemar tests, and multivariate ordinal logistic regression. Results: The main causes of patients' preoperative fear were surgery (53.2%), potential complications (46.5%), and anesthesia (40%). Female sex was a predictor of surgery and anesthesia-related fear (OR = 3.07, p = 0.001; OR = 2.4, p = 0.001, respectively). Previous experience lowered the fear of current surgery (OR = 0.65, p = 0.031) and anesthesia (OR = 0.6, p = 0.017). Type of surgery, type of anesthesia, educational and socioeconomic status, and personal knowledge of an anesthesiologist affected specific anesthesia-related fears. Over 25% of patients did not know that an anesthesiologist is a physician, and only 17.7% knew where anesthesiologists work. Level of education and place of residence influenced patients' perceptions of anesthesia. Conclusions: Anesthesia-related fears are affected by the type of surgery/anesthesia, experience with previous surgery, and personal knowledge of an anesthesiologist. Women, patients with lower education levels, and patients with poorer socioeconomic status are at higher risk of developing those fears. The perception of anesthesiologists is inadequate, and knowledge of anesthesia is poor. Promotion of patient education regarding anesthesia is needed to alleviate those fears and increase understanding of anesthesia.

Normotensive rats with PCOS exhibit the hypertensive pattern: focus on oxidative stress.

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. In this study, we aimed to investigate the potential strain differences in ovarian morphology, hemodynamic, and biochemical characteristics in an androgen-induced PCOS rat model. A total of 24 rats of 3 weeks old (12 Wistar Kyoto - WK and 12 spontaneously hypertensive rats - SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily s.c. injections of testosterone enanthate (1 mg/100 g body weight) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic, and cystic follicles). Ultrasonographically, a significant decrease in ovarian volume (OV) was registered in PCOS groups but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial, and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, thiobarbituric acid reactive substance and superoxide anion radical levels were higher in both strains, while superoxide dismutase and glutathione were significantly lowered.

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.

ArmAssist Robotic System versus Matched Conventional Therapy for Poststroke Upper Limb Rehabilitation: A Randomized Clinical Trial.

The ArmAssist is a simple low-cost robotic system for upper limb motor training that combines known benefits of repetitive task-oriented training, greater intensity of practice, and less dependence on therapist assistance. The aim of this preliminary study was to compare the efficacy of ArmAssist (AA) robotic training against matched conventional arm training in subacute stroke subjects with moderate-to-severe upper limb impairment. Twenty-six subjects were enrolled within 3 months of stroke and randomly assigned to the AA group or Control group (n = 13 each). Both groups were trained 5 days per week for 3 weeks. The primary outcome measure was Fugl-Meyer Assessment-Upper Extremity (FMA-UE) motor score, and the secondary outcomes were Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS) and Barthel index (BI). The AA group, in comparison to the Control group, showed significantly greater increases in FMA-UE score (18.0 ± 9.4 versus 7.5 ± 5.5, p = 0.002) and WMFT-FAS score (14.1 ± 7.9 versus 6.7 ± 7.8, p = 0.025) after 3 weeks of treatment, whereas the increase in BI was not significant (21.2 ± 24.8 versus 13.1 ± 10.7, p = 0.292). There were no adverse events. We conclude that arm training using the AA robotic device is safe and able to reduce motor deficits more effectively than matched conventional arm training in subacute phase of stroke. The study has been registered at the ClinicalTrials.gov, ID: NCT02729649.

Validating ArmAssist Assessment as outcome measure in upper-limb post-stroke telerehabilitation.

The ArmAssist is a low-cost robotic system for post-stroke upper-limb telerehabilitation based on serious games. The system incorporates a set of games for the assessment of arm function, the ArmAssist Assessment (AAA), which allows a remote monitoring of the progress of the patient and an automatic adaptation of the therapy. In this study, different components of the AAA are compared against three widely-used clinical tests, the Fugl-Meyer Assessment (FMA) [1], the Action Research Arm Test (ARAT) [2] and the Wolf Motor Function Test (WMFT) [3] in order to select the most clinically meaningful ones for the final score provided to patients and therapist, and evaluate their capability to predict or even improve some aspects of these standard scales. All four tests were performed in 38 separate sessions in 19 post-stroke individuals in their sub-acute phase, as part of a broader study. Statistically significant correlation could be shown with the three clinical tests. These preliminary results are promising for the validation of AAA as a fast, automatic and clinically meaningful tool for remote progress assessment and therapy adaptation; however, more data and further analysis is needed to confirm this.

Is it time to test biguanide metformin in the treatment of melanoma?

Metformin is the most widely used antidiabetic drug that belongs to the biguanide class. It is very well tolerated and has the major clinical advantage of not inducing hypoglycemia. Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-activated protein kinase-mammalian target of rapamycin and neoglucogenic genes. The effects of metformin on this pathway results in reduced protein synthesis and cell proliferation. These observations have given the impetus for many investigations on the role of metformin in the regulation of tumor cell proliferation, cell-cycle regulation, apoptosis, and autophagy. Encouraging results from these studies have shown that metformin could potentially be used as an efficient anticancer drug in various neoplasms such as prostate, breast, lung, pancreas cancers, and melanoma. These findings are strengthened by retrospective epidemiological studies that have found a decrease in cancer risk in diabetic patients treated with metformin. In this review, we have focused our discussion on recent molecular mechanisms of metformin that have been described in various solid tumors in general and in melanoma in particular.