The Influence of Emotional Material on Encoding and Retrieving Intentions: An ERP Study in Younger and Older Adults

Prospective memory is a cognitive process that comprises the encoding and maintenance of an intention until the appropriate moment of its retrieval. It is of highly relevance for an independent everyday life, especially in older adults; however, there is ample evidence that prospective memory declines with increasing age. Because most studies have used neutral stimuli, it is still an open question how emotional factors influence age-related differences in prospective remembering. The aim of the study was to investigate the influence of emotional material on prospective memory encoding, monitoring, maintaining, and retrieval in younger and older adults using behavioral and electrophysiological measures. We tested 24 younger adults (M = 26.4 years) and 20 older adults (M = 68.1 years) using a picture one-back task as ongoing activity with an embedded prospective memory instruction. The experimental task consisted of three sessions. In each session, participants had to encode series of images that represented the prospective memory cues for the consecutive block. The images were either of pleasant, unpleasant, or neutral valence. The pictures used in the ongoing task were likewise of pleasant, unpleasant, or neutral valence. Event-related potentials (ERPs) were recorded to assess the neural correlates of intention encoding, maintenance, and self-initiated retrieval. We did not find age differences between younger and older adults on the behavioral level. However, the ERP results revealed an interesting pattern that suggested for both age groups elevated attentional processing of emotional cues during encoding indicated by an elevated LPP for the emotional cues. Additionally, younger adults showed increased activity for unpleasant cues. During the maintenance phase, both age groups engaged in strategic monitoring especially for pleasant cues, which led to enhanced sustained positivity. During retrieval, older adults showed increased activity of ERP components related to cue detection and retrieval mainly for pleasant cues indicating enhanced relevance for those cues. In conclusion, emotional material may influence prospective remembering in older adults differently than in younger adults by supporting a mixture of top-down and bottom-up controlled processing. The results demonstrated a negativity bias in younger adults and a positivity bias in older adults

Transcranial random noise stimulation (tRNS): a wide range of frequencies is needed for increasing cortical excitability

Transcranial random noise stimulation (tRNS) is a recent neuromodulation protocol. The high-frequency band (hf-tRNS) has shown to be the most effective in enhancing neural excitability. The frequency band of hf-tRNS typically spans from 100 to 640 Hz. Here we asked whether both the lower and the higher half of the high-frequency band are needed for increasing neural excitability. Three frequency ranges (100\u2013400 Hz, 400\u2013700 Hz, 100\u2013700 Hz) and Sham conditions were delivered for 10 minutes at an intensity of 1.5 mA over the primary motor cortex (M1). Single-pulse transcranial magnetic stimulation (TMS) was delivered over the same area at baseline, 0, 10, 20, 30, 45 and 60 minutes after stimulation, while motor evoked potentials (MEPs) were recorded to evaluate changes in cortical excitability. Only the full-band condition (100\u2013700 Hz) was able to modulate excitability by enhancing MEPs at 10 and 20 minutes after stimulation: neither the higher nor the lower sub-range of the high-frequency band significantly modulated cortical excitability. These results show that the efficacy of tRNS is strictly related to the width of the selected frequency range

Theta and alpha oscillations as signatures of internal and external attention to delayed intentions: A magnetoencephalography (MEG) study

Background: Remembering to execute delayed intentions (i.e., prospective memory, PM) entails the allocation of internal and external attention. These processes are crucial for rehearsing PM intentions in memory and for monitoring the presence of the PM cue in the environment, respectively. Aim: The study took advantage of the excellent spatial and temporal resolution of magnetoencephalography (MEG) to delineate the neural mechanisms of the memory and monitoring processes underlying PM. Method: The spatio-temporal dynamic of theta and alpha oscillations were explored in 21 participants in two PM tasks compared to a baseline condition (i.e., a lexical decision task with no PM instruction). The PM tasks varied for the load of internally-directed attention (Retrospective-load task) vs externally-directed attention (Monitoring-load task). Results: Increase in theta activity was observed in the Retrospective-load task, and was particularly expressed in the regions of the Default Mode Network, such as in medial temporal regions, precuneus, posterior cingulate cortex and medial prefrontal cortex. Alpha decrease was the most relevant feature of the Monitoring-load task, and it was expressed over bilateral occipital, occipito-parietal and fronto-temporal regions, as well as over left dorsal fronto-parietal regions. Conclusions: Theta and alpha oscillations are strictly associated with the direction of attention during the PM tasks. In particular, theta increase is linked to internal attention necessary for maintaining the intention active in working memory, whereas alpha decrease supports the external attention for detecting the PM cue in the environment

A Quantitative Estimate of the Expected Shortening of the Median Isolation Period of Patients With COVID-19 After the Adoption of a Symptom-Based Strategy

A long period of isolation was observed in patients hospitalized for COVID-19 in Milan over March-September 2020 (45; IQR: 37–54 days). A significantly shorter period would have been observed by the application of May-WHO (22, IQR: 17–30 days, P < 0.001) and October-Italian (26, IQR: 21–34 days, P < 0.001) Guidelines. The adoption of the new symptom-based criteria is likely to lead to a significant reduction in the length of the isolation period with potential social, economic and psychological benefits, particularly in the younger population with mild/moderate disease and no comorbidities. In our opinion, the release from isolation after 21 days from symptoms onset, even without a PCR diagnostic test, in most cases seems the most adequate strategy that could balance precautions to prevent SARS CoV-2 transmission and unnecessary prolonged isolation or overuse of diagnostic testing

Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae. Results from a multicentre retrospective study

Introduction The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam +/- other). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam +/- other). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS &gt;= 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens

The importance of patients' case-mix for the correct interpretation of the hospital fatality rate in COVID-19 disease

OBJECTIVE: We aimed to document data on the epidemiology and factors associated with clinical course leading to death of patients hospitalised with COVID-19. METHODS: Prospective observational cohort study on patients hospitalised with COVID-19 disease in February-24th/May-17th 2020 in Milan, Italy. Uni-multivariable Cox regression analyses were performed. Death's percentage by two-weeks' intervals according to age and disease severity was analysed. RESULTS: A total of 174/539 (32.3%) patients died in hospital over 8228 person-day follow-up; the 14-day Kaplan-Meier probability of death was 29.5% (95%CI: 25.5-34.0). Older age, burden of comorbidities, COVID-19 disease severity, inflammatory markers at admission were independent predictors of increased risk, while several drug-combinations were predictors of reduced risk of in-hospital death. The highest fatality rate, 36.5%, occurred during the 2nd-3rd week of March, when 55.4% of patients presented with severe disease, while a second peak, by the end of April, was related to the admission of older patients (55% ≥80 years) with less severe disease, 30% coming from long-term care facilities. CONCLUSIONS: The unusual fatality rate in our setting is likely to be related to age and the clinical conditions of our patients. These findings may be useful to better allocate resources of the national healthcare system, in case of re-intensification of COVID-19 epidemics

Combination of baseline LDH, performance status and age as integrated algorithm to identify solid tumor patients with higher probability of response to anti PD-1 and PD-l1 monoclonal antibodies

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti-Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables\u2019 effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient\u2019s response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients

The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of platinum-based chemotherapy in patients with metastatic triple negative breast cancer

Platinum salts are active against metastatic triple negative breast cancer (mTNBC), and biomarkers to predict their effectiveness are urgently needed. In recent years, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have emerged as prognostic biomarkers in many malignancies, but their predictive role in platinum-treated mTNBC patients remains unexplored. We performed a retrospective, single centre study to evaluate the association between baseline NLR or PLR and progression free survival (PFS) of mTNBC patients treated with platinum-based chemotherapy. As a control population, we analysed data from patients with hormone receptor-positive HER2-negative (HR+ HER2-) metastatic breast cancer. Among 57 mTNBC patients treated with the carboplatin-paclitaxel or carboplatin-gemcitabine combination, high NLR and PLR were associated with significantly lower PFS at both univariate and multivariable analysis. Conversely, we did not find a significant association between NLR or PLR and the PFS of 148 patients in the control population. Our findings suggest that the NLR and PLR are predictive of benefit from platinum-containing chemotherapy specifically in mTNBC patients. If validated in larger prospective studies, these easy-to-measure parameters could be combined with emerging predictive biomarkers, such as BRCA 1/2 mutations, to improve the selection of mTNBC patients more likely to benefit from platinum-based chemotherapy

Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors

New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization at submicromolar concentration and inhibited cell growth at low nanomolar concentrations. Compounds 18 and 57 were superior to the previously synthesized 5. Compound 18 was exceptionally potent as an inhibitor of cell growth: it showed IC₅₀ = 1.0 nM in MCF-7 cells, and it was uniformly active in the whole panel of cancer cells and superior to colchicine and combretastatin A-4. Compounds 18, 20, 55, and 57 were notably more potent than vinorelbine, vinblastine, and paclitaxel in the NCI/ADR-RES and Messa/Dx5 cell lines, which overexpress P-glycoprotein. Compounds 18 and 57 showed initial vascular disrupting effects in a tumor model of liver rhabdomyosarcomas at 15 mg/kg intravenous dosage. Derivative 18 showed water solubility and higher metabolic stability than 5 in human liver microsomes