Parietal tACS at beta frequency improves vision in a crowding regime

Abstract Visual crowding is the inability to discriminate objects when presented with nearby flankers and sets a fundamental limit for conscious perception. Beta oscillations in the parietal cortex were found to be associated to crowding, with higher beta amplitude related to better crowding resilience. An open question is whether beta activity directly and selectively modulates crowding. We employed transcranial alternating current stimulation (tACS) in the beta band (18-Hz), in the alpha band (10-Hz) or in a sham regime, asking whether 18-Hz tACS would selectively improve the perception of crowded stimuli by increasing parietal beta activity. Resting electroencephalography (EEG) was measured before and after stimulation to test the influence of tACS on endogenous oscillations. Consistently with our predictions, we found that 18-Hz tACS, as compared to 10-Hz tACS and sham stimulation, reduced crowding. This improvement was found specifically in the contralateral visual hemifield and was accompanied by an increased amplitude of EEG beta oscillations, confirming an effect on endogenous brain rhythms. These results support a causal relationship between parietal beta oscillations and visual crowding and provide new insights into the precise oscillatory mechanisms involved in human vision

Shaping prestimulus neural activity with auditory rhythmic stimulation improves the temporal allocation of attention.

Human attention fluctuates across time, and even when stimuli have identical physical characteristics and the task demands are the same, relevant information is sometimes consciously perceived and at other times not. A typical example of this phenomenon is the attentional blink, where participants show a robust deficit in reporting the second of two targets (T2) in a rapid serial visual presentation (RSVP) stream. Previous electroencephalographical (EEG) studies showed that neural correlates of correct T2 report are not limited to the RSVP period, but extend before visual stimulation begins. In particular, reduced oscillatory neural activity in the alpha band (8-12 Hz) before the onset of the RSVP has been linked to lower T2 accuracy. We therefore examined whether auditory rhythmic stimuli presented at a rate of 10 Hz (within the alpha band) could increase oscillatory alpha-band activity and improve T2 performance in the attentional blink time window. Behaviourally, the auditory rhythmic stimulation worked to enhance T2 accuracy. This enhanced perception was associated with increases in the posterior T2-evoked N2 component of the event-related potentials and this effect was observed selectively at lag 3. Frontal and posterior oscillatory alpha-band activity was also enhanced during auditory stimulation in the pre-RSVP period and positively correlated with T2 accuracy. These findings suggest that ongoing fluctuations can be shaped by sensorial events to improve the allocation of attention in time.This work was supported by a UK Medical Research Council grant G90951 (DS).This is the final version of the article. It first appeared from Wolters Kluwer via https://doi.org/10.1097/WNR.000000000000056

Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial

BACKGROUND: The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone. PATIENTS AND METHODS: Patients randomly received CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI at the clinician's discretion. RESULTS: Out of the 284 patients enrolled, increased ALRI levels were associated with shorter PFS and OS (p<0.0001). At baseline, median PFS was 10.3 months (95% CI 9.4-12.0) and 8.0 months (95 % CI 6.8-8.9), and median OS was 25.2 months (95 % CI 21.3-30.2) and 18.8 months (95 % CI 16.6-21.7) for patients with low (<14) and high (≥14) ALRI levels, respectively (HR 1.43, 95% CI 1.12-1.82, p=0.004; HR=1.51, 95% CI 1.17-1.96, p<0.001). Interaction tests on ALRI levels and treatment efficacy in the CT+B and the CT groups were statistically significant for PFS (p=0.0003), but not for OS (p=0.228). CONCLUSION: Our results indicate that ALRI is a good prognostic and predictive marker for mCRC patients candidate for CT+B

Synthesis, characterisation and photochemistry of PtIV pyridyl azido acetato complexes

PtII azido complexes [Pt(bpy)(N3)2] (1), [Pt(phen)(N3)2] (2) and trans-[Pt(N3)2(py)2] (3) incorporating the bidentate diimine ligands 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen) or the monodentate pyridine (py) respectively, have been synthesised from their chlorido precursors and characterised by X-ray crystallography; complex 3 shows significant deviation from square-planar geometry (N3–Pt–N3 angle 146.7°) as a result of steric congestion at the Pt centre. The novel PtIV complexes trans, cis-[Pt(bpy)(OAc)2(N3)2] (4), trans, cis-[Pt(phen)(OAc)2(N3)2] (5), trans, trans, trans-[Pt(OAc)2(N3)2(py)2] (6), were obtained from 1–3via oxidation with H2O2 in acetic acid followed by reaction of the intermediate with acetic anhydride. Complexes 4–6 exhibit interesting structural and photochemical properties that were studied by X-ray, NMR and UV-vis spectroscopy and TD-DFT (time-dependent density functional theory). These PtIV complexes exhibit greater absorption at longer wavelengths (ε = 9756 M−1 cm−1 at 315 nm for 4; ε = 796 M−1 cm−1 at 352 nm for 5; ε = 16900 M−1 cm−1 at 307 nm for 6, in aqueous solution) than previously reported PtIV azide complexes, due to the presence of aromatic amines, and 4–6 undergo photoactivation with both UVA (365 nm) and visible green light (514 nm). The UV-vis spectra of complexes 4–6 were calculated using TD-DFT; the nature of the transitions contributing to the UV-vis bands provide insight into the mechanism of production of the observed photoproducts. The UV-vis spectra of 1–3 were also simulated by computational methods and comparison between PtII and PtIV electronic and structural properties allowed further elucidation of the photochemistry of 4–6

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

The deployment of visual attention in autism spectrum disorders

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition that affects almost 1% of the population. One of the main challenges in the current ASD research is to define the early neurocognitive impairments that provide critical foundations for the core deficits in social and communication abilities. In particular, early attentional dysfunctions may play a critical role in the emergence of ASD. In this doctoral thesis I present six studies that give significant new insights into the nature of altered visual attention in individuals with ASD and their possible neural underpinnings. In the first study we show that individuals with ASD are impaired in enlarging (i.e., “zooming-out”) the attentional focus size relative to the control group and this deficit can impact the rapid orienting toward a cued location in the visual field. The second and the third studies show how parents without any history of ASD but with elevated autistic traits can transmit to their infants subtle deficit in visual attention (at the expense of both orienting and zooming mechanism) that may impact children’s future socio-communicative abilities. In the fourth and the fifth studies we employed transcranial magnetic stimulation and dense-array electroencephalography, respectively, with typical adults participants and we show that a network of frontal (mainly FEF and IFG) and parietal (mainly IPS/SPL) brain areas are fundamental in regulating the size of the attentional focus. In the last study, we evaluated the spatial profile of the attentional focus in individuals with ASD and results show that the inhibitory ring outside the focus of attention – fundamental to attenuate processing of irrelevant information – is significantly weakened relative to the control group. Overall, these findings show the importance of attentional impairments in the core manifestations of ASD and in its developmental course. Defining attentional abnormalities and their neural correlates is extremely important (i) to improve the early detection of the disorder and, (ii) to implement timely prevention programs to reduce the incidence of ASD.Il disturbo dello spettro autistico (DSA) è un disturbo neuroevolutivo pervasivo che colpisce quasi l'1% della popolazione. Una delle principali sfide nell'attuale ricerca sul DSA è definire i deficit neurocognitivi precoci che costituiscono le fondamenta dei disturbi "chiave" nelle abilità sociali e comunicative. In particolare, precoci disfuzioni attentive potrebbero giocare un ruolo decisivo nell'emergere del DSA. Nella presente tesi di dottorato presento sei studi che contribuiscono significativamente alla comprensione delle alterazioni dell'attenzione visiva nei DSA e le loro possibili basi neurali. Nel primo studio, mostriamo che gli individui affetti da DSA sono compromessi nell'abilità di allargare ("zoom-out") la dimensione del fuoco attentivo e che questo problema può avere un impatto negativo nell'orientamento rapido verso una posizione segnalata nel campo visivo. Il secondo e terzo studio mostrano come genitori senza alcuna storia clinica di DSA ma con elevati tratti autistici possano trasmettere ai loro infanti sottili alterazioni nell'attenzione visiva (a carico sia del meccanismo di orientamento che di quello di zoom) che possono avere conseguenze negative sul futuro sviluppo delle abilità socio-comunicative dei loro figli. Nel quarto e quinto studio, abbiamo utilizzato la stimolazione magnetica transcranica e l'elettroencefalografia ad alta densità, rispettivamente, in partecipanti adulti a sviluppo tipico e mostriamo che un network di aree frontali (principalmente FEF e IFG) e parietali (principalmente IPS/SPL) sono fondamentali nella regolazione della dimensione del fuoco attentivo. Nell'ultimo studio, abbiamo valutato il profilo spaziale del fuoco attentivo in individui con DSA e mostriamo come l'anulo inibitorio circostante al fuoco attentivo – fondamentale per attenuare il processamento d'informazioni irrilevanti – è significativamente più debole nel DSA rispetto al gruppo di controllo. Complessivamente, queste evidenze mostrano l'importanza dei deficit attentivi nelle manifestazioni chiave del DSA e nel suo decorso evolutivo. Definire le anomalie dell'attenzione e i corrispondenti correlati neurali è estremamente importante (i) per migliorare la diagnosi precoce del disturbo e (ii) per implementare tempestivi programmi preventivi mirati a ridurre l'incidenza dei DSA

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Glucose is a key source of energy and an essential nutrient for cell growth. Rapidly dividing cancer cells are well-known to require more nutrients and energy than normal ones to sustain their higher proliferation rates, and glucose is no exception. Therefore, the biomolecules involved in the promotion/regulation of the glycolytic flux may be regarded as potential targets for tackling tumor progression. Among all, glucose transporters (GLUTs), devoted to the recognition and cellular internalization of glucose, are largely overexpressed in tumors, thus indicating glycolysis as the major anaerobic glucose metabolism. Accordingly, such increased demand of glucose by fast-proliferating cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) so as to attain the site-specific delivery of drugs into the affected tissues. Progress in the development of metal-based glycoconjugates are here summarized and discussed.Financial support by the National University of Ireland Galway (College of Science Postgraduate Research Scholarship to AP and RP; Millennium Fund Minor Project 2013 to LR), and the COST Action CM1105 - Functional metal complexes that bind to biomolecules (Short Term Scientific Mission - STSM Grant to RP) is gratefully acknowledged.Peer reviewe