Sex-Related Memory Recall and Talkativeness for Emotional Stimuli

Recent studies have evidenced an increasing interest in sex-related brain mechanisms and cerebral lateralization subserving emotional memory, language processing, and conversational behavior. We used event-related-potentials (ERP) to examine the influence of sex and hemisphere on brain responses to emotional stimuli. Given that the P300 component of ERP is considered a cognitive neuroelectric phenomenon, we compared left and right hemisphere P300 responses to emotional stimuli in men and women. As indexed by both amplitude and latency measures, emotional stimuli elicited more robust P300 effects in the left hemisphere in women than in men, while a stronger P300 component was elicited in the right hemisphere in men compared to women. Our findings show that the variables of sex and hemisphere interacted significantly to influence the strength of the P300 component to the emotional stimuli. Emotional stimuli were also best recalled when given a long-term, incidental memory test, a fact potentially related to the differential P300 waves at encoding. Moreover, taking into account the sex-related differences in language processing and conversational behavior, in the present study we evaluated possible talkativeness differences between the two genders in the recollection of emotional stimuli. Our data showed that women used a higher number of words, compared to men, to describe both arousal and neutral stories. Moreover, the present results support the view that sex differences in lateralization may not be a general feature of language processing but may be related to the specific condition, such as the emotional content of stimuli

Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions: We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients

Dual PI3 K/mTOR inhibition reduces prostate cancer bone engraftment altering tumor-induced bone remodeling:

Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions. We observed that X480 both inhibited the primary growth of subcutaneous tumors generated by PC3 and 22rv1 cells and reduced bone spreading of PCb2, a high osteotropic PC3 cell derivative. In metastatic bone, X480 inhibited significantly the growth and osteolytic activit..

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms

Aim To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis. METHODS Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylateduncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire. RESULTS Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 \u3bc g/L vs 4.2 \u3bc g/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein ( f = 0.220, R 2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls. CONCLUSION SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures

Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES). a multicentre, open-label, randomised trial

Background: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. Methods: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. Findings: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. Interpretation: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. Funding: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy

Challenges in Higher Education. Teaching Innovation between Experimentation and Standardization

The paper aims to investigate some challenges in the academic profession by focusing on innovative teaching practices. An exploration will be carried out on how teaching innovations is accomplished through collective and individual organizing during daily practices. By analyzing findings from the field about the governance of teaching as well as its ongoing transformation, the paper highlights new interweaving between teaching practices and organizational work in the academic profession. Teaching emerges as an autonomous sphere of governance, as a new organizational field in which opposing forces move. Managerial and accountability logic proceeds simultaneously with innovative teaching practices, forms of resistance, and new organizational formulas introduced by the actors from below. Starting from the exploration of the field, in the paper we discuss some emerging critical issues

Introduction

When, in the last months of 2018, we started conceiving this Special issue, we could never have guessed that it would have been published in the middle of a global pandemic. Nor could have we imagined that higher education would have been involved in such an unexpected, previously inconceivable and potent process. Universities around the world are at the forefront right now. They have radically transformed their way of ‘being academia’, since their activities had to be transposed to digital platforms for distance learning. Higher education institutions, which are most exposed to transformation processes, are currently undergoing changes that effect students, policies, security, and more. As shall we described in this Special issue, the pandemic is indeed transforming university life. Today, we can only see the most uncertain and dramatic part of it. Many practices shall undergo restructurings, as will the academic profession, the students’ experience, and research policies. On all these issues we will continue to research in order to understand our world and accompany its transformations

The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task

In this study, the effects on memory of intraperitoneal post-training administration of cyclic nucleotide phosphodiesterase (PDE) inhibitors, DC-TA 46 and rolipram, were tested using a visible/hidden-platform water maze task. The effects of these compounds on cyclic nucleotide levels in the hippocampal formation (HF) and striatum (CP) were also assessed, by enzymatic immunoassay (EIA). The results obtained from rats trained in the visible-platform task were not significantly different from controls. On the contrary, the animals trained in the hidden-platform water maze task showed a memory impairment, when injected with DC-TA 46 at maximal dose of 20 mg/kg and with rolipram at 3 and 30 mg/kg doses. The effects of these drugs on cyclic nucleotide levels in HF and CP were observed at 30 min and at 24 h after drug administration. Thirty minutes after drug injection, we observed an increase of cAMP level, both in HF and in CP. Twenty-four hours after the retention test, we observed that in CP the cAMP intracellular level remained high, while in the HF at effective doses both inhibitors induced cAMP PDE activity, determining a decrease of cyclic nucleotide. Semi-quantitative RT–PCR analysis, together with Western blot immunodetection, showed a mRNA and protein induction of PDE4D PDE isoforms, that may account for the increase of PDE activity observed. Our data suggest that, despite cyclic nucleotide increase at 30 min, the fundamental event causing memory impairment, came from the subsequent long time decrease of cAMP levels, due to the post-translational PDE4D induction

Declarative Memory Impairment and Emotional Bias in Recurrent Depression with a Seasonal Pattern: The Interplay between Emotion and Cognition in Seasonal Affective Disorder

Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder (MDD) with a seasonal pattern. Although it is a pathological condition limited to specific seasons of the year, during the symptomatic period, patients may experience a significant impairment of well-being and daily quality of life as a result of the depressed mood, associated with other symptoms defined as atypical of MDD. While extensive evidence of memory deficits has been found in MDD, explicit memory impairments in SAD are insufficiently studied. This study aims to investigate the cognitive processing of emotional stimuli in women with SAD, in particular the interplay between emotions and declarative memory. One hundred and twenty young women, screened from an initial number of 1125 university students, were divided into two groups, an experimental one that included 60 medically untreated women affected by “winter type SAD” and a control group of 60 non-SAD women. Different subjects were randomly submitted to two types of audio–visual stories, neutral or arousal, and then their memory performances were analyzed by means of a free-recall test and a recognition memory test. In both the free-recall test (p p < 0.002), the SAD group showed impaired memory performances. Taken together, our novel key findings suggest that SAD is characterized by impairment in declarative memory and attentional bias for emotional negative stimuli