Alternating Electric Fields (Tumor-Treating Fields Therapy) Can Improve Chemotherapy Treatment Efficacy in Non-Small Cell Lung Cancer Both In Vitro and In Vivo

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease

Orally Administrated Cinnamon Extract Reduces β-Amyloid Oligomerization and Corrects Cognitive Impairment in Alzheimer's Disease Animal Models

An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet

The perceived vulnerability to disease scale: Cross‐cultural measurement invariance and associations with fear of COVID‐19 across 16 countries

Using cross‐sectional data from N = 4274 young adults across 16 countries during the COVID‐19 pandemic, we examined the cross‐cultural measurement invariance of the perceived vulnerability to disease (PVD) scale and tested the hypothesis that the association between PVD and fear of COVID‐19 is stronger under high disease threat [that is, absence of COVID‐19 vaccination, living in a country with lower Human Development Index (HDI) or higher COVID‐19 mortality]. Results supported a bi‐factor Exploratory Structural Equation Modeling model where items loaded on a global PVD factor, and on the sub‐factors of Perceived Infectability and Germ Aversion. However, cross‐national invariance could only be obtained on the configural level with a reduced version of the PVD scale (PVD‐r), suggesting that the concept of PVD may vary across nations. Moreover, higher PVD‐r was consistently associated with greater fear of COVID‐19 across all levels of disease threat, but this association was especially pronounced among individuals with a COVID‐19 vaccine, and in contexts where COVID‐19 mortality was high. The present research brought clarity into the dimensionality of the PVD measure, discussed its suitability and limitations for cross‐cultural research, and highlighted the pandemic‐related conditions under which higher PVD is most likely to go along with psychologically maladaptive outcomes, such as fear of COVID‐19

Data_Sheet_1_Anger at work.pdf

What happens when you express anger at work? A large body of work suggests that workers who express anger are judged to be competent and high status, and as a result are rewarded with more status, power, and money. We revisit these claims in four pre-registered, well-powered experiments (N = 3,852), conducted in the US, using the same methods used in previous work. Our findings consistently run counter to the current consensus regarding anger's positive role in obtaining status and power in the workplace. We find that when men and women workers express anger they are sometimes viewed as powerful but they are consistently viewed as less competent. Importantly, we find that angry workers are penalized with lower status compared to workers expressing sadness or no emotions. We explore the reasons for these findings both experimentally and descriptively and find that anger connotes less competence and warmth and that anger expressions at work are perceived as inappropriate, an overreaction, and as a lack of self-control. Moreover, we find that people hold negative attitudes toward workplace anger expressions, citing them as relatively more harmful, foolish, and worthless compared to other emotional expressions. When we further explore beliefs about what can be accomplished by expressing anger at work, we find that promoting one's status isn't one of them. We discuss the theoretical and applied implications of these findings and point to new directions in the study of anger, power, and the workplace.</p

Study 3: Emotionality Judgments of Happiness Sequences

The goal of Study 3 was to replicate the effect of target gender on judgments of emotionality from Study 2 using expressions of happiness

Study 2: Emotionality Judgments of Anger Sequences

The goal of Study 2 was to test whether sequences of female faces are more likely to be judged as emotional compared to sequences of male faces

Study 1: Stereotype Survey

The goal of Study 1 was to ascertain if the stereotype that women are more emotional than men persists and if gender-emotion stereotypes vary for different discrete emotions