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Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results. Environmental and reproductive factors may further jeopardize the sex-related heterogeneity in anticancer immune response. In particular, pregnancy is characterized by orchestrated changes in the immune system, some of which could be long lasting. A persistence of memory T-cells with a potential fetal-antigen specificity has been reported both in human and mice, suggesting that a previous pregnancy may positively impact cancer development or response to ICI, in case of fetal-antigen sharing from tumor cells. On the other hand, a previous pregnancy may also be associated with a regulatory memory characterized by increased tolerance and anergy towards cancer-fetal common antigens. Finally, fetal-maternal microchimerism could represent an additional source of chronic exposure to fetal antigens and may have important immunological implications on cancer development and ICI activity. So far, the role of pregnancy dimorphism (nulliparous vs parous) in women and the impact of pregnancy-related variables remain largely underexplored in cancer patients. In this review, we summarize the evidence regarding sex and pregnancy dimorphism in the context of immune response and anticancer immunotherapy and advocate the importance of analyzing pregnancy variables on ICIs clinical trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Maria Venanzi: no conflict of interest to this manuscript. Marta Bini no conflict of interest to this manuscript. Antonio Nuccio no conflict of interest to this manuscript. Alessandro De Toma: no conflict of interest to this manuscript. Matteo Lambertini: advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda, Travel Grants from Gilead and research support (to the Institution) from Gilead outside the submitted work. Francesca Rita Ogliari: no conflict of interest to this manuscript. Sara Oresti: no conflict of interest to this manuscript. Maria Grazia Viganò: no conflict of interest to this manuscript. Elena Brioschi: no conflict of interest to this manuscript. Maggie Polignano: no conflict of interest to this manuscript. Matteo Maria Naldini: no conflict of interest to this manuscript. Silvia Riva: no conflict of interest to this manuscript. Michele Ferrara: no conflict of interest to this manuscript. Nicola Fogale: no conflict of interest to this manuscript. Giuseppe Damiano: no conflict of interest to this manuscript. Vincenzo Russo: no conflict of interest to this manuscript. Michele Reni: no conflict of interest to this manuscript. Giulia Veronesi: no conflict of interest to this manuscript. Giorgia Foggetti: no conflict of interest to this manuscript. Fabio Conforti: no conflict of interest to this manuscript. Alessandra Bulotta: no conflict of interest to this manuscript. Roberto Ferrara: advisory board MSD and Beigene., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Millions of COVID-19 survivors experience a wide range of long-term symptoms after acute infection, giving rise to serious public health concerns. To date, few risk factors for post-COVID-19 conditions have been determined. This study evaluated the role of pre-infection sleep quality/duration and insomnia severity in the incidence of long-term symptoms after COVID-19., Material and Methods: This prospective study involved two assessments (April 2020 and 2022). At the baseline (April 2020), sleep quality/duration and insomnia symptoms in participants without current/prior SARS-CoV-2 infection were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). At the follow-up (April 2022), we asked a group of COVID-19 survivors to retrospectively evaluate the presence of twenty-one symptoms (psychiatric, neurological, cognitive, bodily, and respiratory) that have been experienced one month (n = 713, infection in April 2020-February 2022) and three months after COVID-19 (n = 333, infection in April 2020-December 2021). In April 2022, participants also reported how many weeks passed to fully recover from COVID-19. Zero-inflated negative binomial models were used to estimate the effect of previous sleep on the number of long-term symptoms. Binomial logistic regressions were performed to evaluate the association between sleep variables, the incidence of each post-COVID-19 symptom, and the odds of recovery four/twelve weeks after infection., Results: Analyses highlighted a significant effect of pre-infection sleep on the number of symptoms one/three months after COVID-19. Previous higher PSQI and ISI scores, and shorter sleep duration significantly increased the risk of almost every long-term symptom at one/three months from COVID-19. Baseline sleep problems were also associated with longer recovery times to return to the pre-infection daily functioning level after COVID-19., Conclusions: This study suggested a prospective dose-dependent association of pre-infection sleep quality/quantity and insomnia severity with the manifestation of post-COVID-19 symptoms. Further research is warranted to determine whether preventively promoting sleep health may mitigate the COVID-19 sequelae, with substantial public health and societal implications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Objective: This study aimed to evaluate the learning curve of vaginal natural orifice transuminal endoscopic surgery (vNOTES) hysterectomy in expert minimal invasive and vaginal surgery team., Design: This is a cohort study on a retrospective analysis., Setting: Department of Obstetrics and Gynecology of Cannizzaro Hospital in Catania Italy., Patients: First 50 women underwent vNOTES hysterectomy between February 2021 and February 2022., Intervention: vNOTES hysterectomy performed by a team with optimal skills in laparoscopic and vaginal surgery., Measurement and Main Results: Primary outcome was surgical time. Secondary outcomes were intraoperative and postoperative complications, length of hospitalization, and first 24-hour postoperative pain. All patients underwent hysterectomy for benign indications: 27 fibromatosis, 13 metrorrhagia, and 10 precancerous. Concomitant procedures have been bilateral adnexectomy in 35 cases and bilateral salpingectomy in 15 cases. The median age was 51 years (range, 42-64). Median body mass index was 26 kg/m 2 (range, 21-42). The median operative time was 75 minutes (range, 40-110). The median hospital stay was 2 days (range, 1-4). There was 1 intraoperative adverse event (bladder lesion) and 1 postoperative grade 3 complication (hemoperitoneum). The median visual analog scale score for pain assessment during the first 24 hours after surgery was 3 (range, 1-6). The experience in our surgical center with the first 25 vNOTES hysterectomies showed an accumulation of initial experience in the first 5 cases with stable operating time and a gradual reduction of mean operating time in the subsequent 17 surgeries. The learning curve plotted by cumulative sum analysis shows 3 phases: phase 1 of competence (cases 1-5), phase 2 of proficiency (cases 6-26), and phase 3 of mastering the procedure (after the 31st case) with the management of more complex cases., Conclusion: vNOTES hysterectomy is a feasible and reproducible approach for benign indications with a short learning curve and low rate of perioperative complications. For a team skilled in minimally invasive surgery, 5 cases are required to rich competence and 25 to rich proficiency in vNOTES hysterectomy. Mastering phase, with the introduction of more complex cases, should be addressed after 30 surgeries., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflict of interest.

In 2019, a novel type of coronavirus emerged in China called SARS-COV-2, known COVID-19, threatens global health and possesses negative impact on people's quality of life, leading to an urgent need for its diagnosis and remedy. On the other hand, the presence of hazardous infectious waste led to the increase of the risk of transmitting the virus by individuals and by hospitals during the COVID-19 pandemic. Hence, in this review, we survey previous researches on nanomaterials that can be effective for guiding strategies to deal with the current COVID-19 pandemic and also decrease the hazardous infectious waste in the environment. We highlight the contribution of nanomaterials that possess potential to therapy, prevention, detect targeted virus proteins and also can be useful for large population screening, for the development of environmental sensors and filters. Besides, we investigate the possibilities of employing the nanomaterials in antiviral research and treatment development, examining the role of nanomaterials in antiviral- drug design, including the importance of nanomaterials in drug delivery and vaccination, and for the production of medical equipment. Nanomaterials-based technologies not only contribute to the ongoing SARS- CoV-2 research efforts but can also provide platforms and tools for the understanding, protection, detection and treatment of future viral diseases., Competing Interests: All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (© 2021 Elsevier Ltd. All rights reserved.)

Background: Pheochromocytoma and paraganglioma (PPGL) have currently only limited treatment options available for patients in the metastatic phase (mPPGL) in either post-surgery or inoperable settings. However, these rare tumors overexpress somatostatin receptors and can thus be treated with peptide receptor radionuclide therapy (PRRT). We present data about our 10-year experience treating 46 consecutive mPPGL patients with 90Y-DOTATOC or 177Lu-DOTATATE., Patients and Methods: All patients (20 men and 26 women, median age 52 years) showed positive scintigraphic imaging at 111In-octreotide or 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT). 90Y-DOTATOC was administered in 12 patients, with cumulative dosages ranging from 7.4 to 11 GBq, while 34 patients received 18.5 or 27.5GBq of 177Lu-DOTATATE. We used Southwest Oncology Group Response Evaluation Criteria in Solid Tumors criteria to evaluate treatment efficacy and Common Terminology Criteria for Adverse Events criteria to assess toxicity. The prognostic role of primary tumor site, hormone secretion, succinate dehydrogenase (SDHx) mutation, and metastatic involvement was also evaluated., Results: Both 90Y-DOTATOC and 177Lu-DOTATATE PRRT were well tolerated by patients without significant renal or bone marrow toxicity. The median follow-up was 73 months (range 5-146 months). The overall disease control rate (DCR) was 80% [95% confidence interval (CI) 68.9% to 91.9%] with a mean five cycles of therapy. However, 177Lu-DOTATATE patients showed a longer median overall survival (mOS) than those receiving 90Y-Dotatoc and a better DCR when higher dosages were administered, even if a direct comparison was not carried out. Syndromic patients had a poorer mOS. SDHx mutations did not interfere with treatment efficacy., Conclusions: PRRT is safe and effective for the treatment of patients with progressive mPPGL, especially at higher dosages. The longer mOS of 177Lu-DOTATATE-treated patients in our protocols indicates the former radiopharmaceutical as the better candidate for further clinical application., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This article focus the elimination and control of the infection caused by COVID-19. Mathematical model of the disease is formulated. With help of sensitivity analysis of the reproduction number the most sensitive parameters regarding transmission of infection are found. Consequently strategies for the control of infection are proposed. Threshold condition for global stability of the disease free state is investigated. Finally, using Matlab numerical simulations are produced for validation of theocratical results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Coronavirus is a pandemic that has become a concern for the whole world. This disease has stepped out to its greatest extent and is expanding day by day. Coronavirus, termed as a worldwide disease, has caused more than 8 lakh deaths worldwide. The foremost cause of the spread of coronavirus is SARS-CoV and SARS-CoV-2, which are part of the coronavirus family. Thus, predicting the patients suffering from such pandemic diseases would help to formulate the difference in inaccurate and infeasible time duration. This paper mainly focuses on the prediction of SARS-CoV and SARS-CoV-2 using the B-cells dataset. The paper also proposes different ensemble learning strategies that came out to be beneficial while making predictions. The predictions are made using various machine learning models. The numerous machine learning models, such as SVM, Naïve Bayes, K-nearest neighbors, AdaBoost, Gradient boosting, XGBoost, Random forest, ensembles, and neural networks are used in predicting and analyzing the dataset. The most accurate result was obtained using the proposed algorithm with 0.919 AUC score and 87.248% validation accuracy for predicting SARS-CoV and 0.923 AUC and 87.7934% validation accuracy for predicting SARS-CoV-2 virus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

In the present study, a nonlinear delayed coronavirus pandemic model is investigated in the human population. For study, we find the equilibria of susceptible-exposed-infected-quarantine-recovered model with delay term. The stability of the model is investigated using well-posedness, Routh Hurwitz criterion, Volterra Lyapunov function, and Lasalle invariance principle. The effect of the reproduction number on dynamics of disease is analyzed. If the reproduction number is less than one then the disease has been controlled. On the other hand, if the reproduction number is greater than one then the disease has become endemic in the population. The effect of the quarantine component on the reproduction number is also investigated. In the delayed analysis of the model, we investigated that transmission dynamics of the disease is dependent on delay terms which is also reflected in basic reproduction number. At the end, to depict the strength of the theoretical analysis of the model, computer simulations are presented., Competing Interests: All the authors have no conflict of interest., (© 2020 The Author(s).)

The outburst of the pandemic Coronavirus disease since December 2019, has severely impacted the health and economy worldwide. The epidemic is spreading fast through various means, as the virus is very infectious. Medical science is exploring a vaccine, only symptomatic treatment is possible at the moment. To contain the virus, it is required to categorize the risk factors and rank those in terms of contagion. This study aims to evaluate risk factors involved in the spread of COVID-19 and to rank them. In this work, we applied the methodology namely, Fuzzy Analytic Hierarchy Process (FAHP) to find out the weights and finally Hesitant Fuzzy Sets (HFS) with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is applied to identify the major risk factor. The results showed that "long duration of contact with the infected person" the most significant risk factor, followed by "spread through hospitals and clinic" and "verbal spread". We showed the appliance of the Multi Criteria Decision Making (MCDM) tools in evaluation of the most significant risk factor. Moreover, we conducted sensitivity analysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

In present time, the whole world is in the phase of war against the deadly pandemic COVID'19 and working on different interventions in this regard. Variety of strategies are taken into account from ground level to the state to reduce the transmission rate. For this purpose, the epidemiologists are also augmenting their contribution in structuring such models that could depict a scheme to diminish the basic reproduction number. These tactics also include the awareness campaigns initiated by the stakeholders through digital, print media and etc. Analyzing the cost and profit effectiveness of these tactics, we design an optimal control dynamical model to study the proficiency of each strategy in reducing the virulence of COVID'19. The aim is to illustrate the memory effect on the dynamics of COVID'19 with and without prevention measures through fractional calculus. Therefore, the structure of the model is in line with generalized proportional fractional derivative to assess the effects at each chronological change. Awareness about using medical mask, social distancing, frequent use of sanitizer or cleaning hand and supportive care during treatment are the strategies followed worldwide in this fight. Taking these into consideration, the optimal objective function proposed for the surveillance mitigation of COVID'19, is contemplated as the cost function. The effect analysis is supported through graphs and tabulated values. In addition, sensitivity inspection of basic reproduction number is also carried out with respect to different values of fractional index and cost function. Ultimately, social distancing and supportive care of infected are found to be significant in decreasing the basic reproduction number more rapidly., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V.)

This work is the consideration of a fractal fractional mathematical model on the transmission and control of corona virus (COVID-19), in which the total population of an infected area is divided into susceptible, infected and recovered classes. We consider a fractal-fractional order SIR type model for investigation of Covid-19. To realize the transmission and control of corona virus in a much better way, first we study the stability of the corresponding deterministic model using next generation matrix along with basic reproduction number. After this, we study the qualitative analysis using "fixed point theory" approach. Next, we use fractional Adams-Bashforth approach for investigation of approximate solution to the considered model. At the end numerical simulation are been given by matlab to provide the validity of mathematical system having the arbitrary order and fractal dimension., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Purpose: The COVID-19 pandemic and related lockdown measures drastically changed health care and emergency services utilization. This study evaluated trends in emergency department (ED) access for seizure-related reasons in the first 8 weeks of lockdown in Italy., Methods: All ED accesses of children (<14 years of age) at two university hospitals, in Turin and Rome, Italy, between January 6, 2020 and April 21, 2020, were examined and compared with the corresponding periods of 2019., Results: During the COVID-19 lockdown period (February 23-April 21, 2020), there was a 72 % decrease in all pediatric ED accesses over the corresponding 2019 period (n = 3,395 vs n = 12,128), with a 38 % decrease in seizure-related accesses (n = 41 vs n = 66). The observed decrease of seizure-related ED accesses was not accompanied by significant changes in age, sex, type of seizure, or hospitalization rate after the ED visit., Conclusion: The COVID-19 lockdown was accompanied by a sudden decrease in seizure-related hospital emergency visits. School closure, social distancing, reduced risk of infection, and increased parental supervision are some of the factors that might have contributed to the finding., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Competing interests: DS has reported honoraria from Merck Sharp & Dohme, Merck, Amgen, Boehringer, Pfizer, Janssen, Astellas, Roche, Ipsen, Novartis, Italfarmaco, Sanofi, Bristol-Myers Squibb and AstraZeneca.

Fumonisins contamination of food commodities is a worldwide problem, especially for maize. The ability to produce fumonisinsis a trait of several species of Fusarium, mainly F. verticillioides and F. proliferatum on maize, and some Aspergillus species. A. niger and its sister species A. welwitschiae, can contribute to fumonisin B 2 (FB 2 ) accumulation in maize kernels, although to a lesser extent than fumonisin-producing Fusarium species. Fumonisins risk monitoring represents an effective strategy in the integrated approach for mycotoxin risk management and reduction. The availability of a user-friendlymolecular assay for the detection oftoxigenic fungal species represents a valuable tool in understanding and managing upcoming mycotoxin contamination. In this study, we developed a LAMP assay, based on the detection of fum10, for a rapid and specific molecular detection of FB 2 -producing A. niger and A. welwistchiae, potentially useful to perform monitoring directly "on site" in maize chain. Results showed that very low amounts of conidia are suitable to detect the presence of the target gene, thus providing information about the presence of FB 2 -producing Aspergillus species and the possible upcoming fumonisins contamination in maize. The assay was combined with a suitable protocol for "in field" crude DNA extraction and a colorimetric method for easy naked-eye evaluationof results, offering a reliable and user-friendly tool to support effective reduction strategies of mycotoxin contamination in crop management programs., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Forty-nine consecutive, drug naïve outpatients with de novo Parkinson's disease (PD) and 12 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) underwent clinical examination and dopamine transporter single photon emission computed tomography with [(123)I]-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane as a biomarker of nigro-striatal function. PD patients were grouped into rapid eye movement sleep behavior disorder (RBD) negative (PD-RBD-) and RBD positive (PD-RBD+). Repeated measures and univariate analysis of variance were used to compare dopaminergic and clinical impairment among groups. The variations of dopamine transporter-single photon emission computed tomography specific binding ratios (SBR) as a function of group belonging were significantly different (p = 0.0013) at caudate with respect to putamen level. Indeed, putamen SBR progressively decreased from iRBD to PD-RBD- and PD-RBD+ groups while caudate SBR were higher in PD-RBD- group than in PD-RBD+ and even than in iRBD group. Motor impairment was more severe in PD patients with RBD than in those without RBD. Our data suggest that a more severe nigro-caudate dopaminergic deafferentation is related to RBD, both in its idiopathic form and in PD patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: People living with HIV infection are disproportionately burdened by trauma and the resultant negative health consequences, making the combination of HIV infection and trauma a syndemic illness. Despite the high co-occurrence and negative influence on health, trauma and posttraumatic sequelae in people living with HIV infection often go unrecognized and untreated because of the current gaps in medical training and lack of practice guidelines., Objective: We set out to review the current literature on HIV infection and trauma and propose a trauma-informed model of care to target this syndemic illness., Methods: We searched PubMed, PsycINFO, and Cochrane review databases for articles that contained the following search terms: HIV AND either trauma (specifically violent trauma), PTSD, intimate partner violence (IPV), abuse, or trauma-informed care. Articles were limited to primary clinical research or metanalyses published in English. Articles were excluded if they referred to HIV-associated posttraumatic stress disorder or HIV-associated posttraumatic growth., Results: We confirm high, but variable, rates of trauma in people living with HIV infection demonstrated in multiple studies, ranging from 10%-90%. Trauma is associated with (1) increased HIV-risk behavior, contributing to transmission and acquisition of the virus; (2) negative internal and external mediators also associated with poor health and high-risk HIV behavior; (3) poor adherence to treatment; (4) poor HIV-related and other health outcomes; and (5) particularly vulnerable special populations., Conclusions: Clinicians should consider using a model of trauma-informed care in the treatment of people living with HIV infection. Its adoption in different settings needs to be matched to available resources., (Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs) in each hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine and the AAL VOIs was tested against a validated method (PALZ). At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed.

Background: Changes of cortical excitability after sleep deprivation (SD) in humans have been investigated mostly in motor cortex, while there is little empirical evidence concerning somatosensory cortex, and its plastic changes across SD., Objective: To assess excitability of primary somatosensory cortex (S1) and EEG voltage topographical characteristics associated with somatosensory evoked potentials (SEPs) during SD., Methods: Across 41 h of SD, 16 healthy subjects participated in 4 experimental sessions (11.00 a.m. and 11.00 p.m. of the 1st and 2nd day) with: a) subjective sleepiness ratings; b) EEG recordings; c) SEPs recordings; d) behavioral vigilance responses., Results: A clear enhancement of cortical excitability after SD was indexed by: (a) an amplitude increase of different SEPs component in S1; (b) higher voltage in occipital (around 35-43 ms) and fronto-central areas (around 47-62 ms). Circadian fluctuations did not affect cortical excitability. Voltage changes in S1 were strongly related with post-SD fluctuations of subjective and behavioral sleepiness., Conclusions: Sleep may have a role in keeping cortical excitability at optimal (namely below potentially dangerous) levels for the human brain, rebalancing progressive changes in cortical responsiveness to incoming inputs occurred during time spent awake. On the other hand, higher level of cortical responsiveness after sleep loss may be one of the mechanisms accounting for post-SD alterations in vigilance and behavior., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: In patients with atrial flutter who undergo cavotricuspid isthmus ablation, long-term electrocardiographic (ECG) monitoring may identify new onset of atrial fibrillation (AF)., Objectives: To ascertain, through the use of an implantable loop recorder (ILR) with a dedicated AF detection algorithm, the incidence, duration, and burden of new AF in these patients and to develop an optimal postablation ECG monitoring strategy., Methods: We enrolled 20 patients with flutter, a CHADS2 score of 2-3, and no prior episode of AF. After cavotricuspid isthmus ablation, we implanted an ILR, which was interrogated routinely; all stored ECGs were adjudicated., Results: During a mean follow-up of 382 ± 218 days, 3 patterns were observed. First, in 11 (55%) patients, stored ECGs confirmed AF at 62 ± 38 days after ablation. Second, in 4 (20%) patients, although the ILR suggested AF, episodes actually represented sinus rhythm with frequent premature atrial contractions and/or oversensing. Third, in 5 (25%) patients, no AF was observed. Episodes <4 hours were associated with low AF burden (<1%) or false detections. The 1-year freedom from any episode of AF >4 and >12 hours was 52% and 83%, respectively., Conclusions: Our data show that many (but not all) patients develop new AF within the first 4 months of flutter ablation. Since external ECG monitoring for this duration is impractical, the ILR has an important role for long-term AF surveillance. Future research should be directed toward identifying the relationship between duration/burden of AF and stroke and improving existing ILR technology., (© 2013 Heart Rhythm Society. All rights reserved.)

Even though bronchiolitis is a disease that has been recognized for many years, there are still few therapeutic strategies beyond supportive therapies. Bronchiolitis is the most frequent cause of hospital admission in children less than 1 year of age. The incidence is estimated to be about 150° million cases a year worldwide, and 2-3% of these cases require hospitalization. It is acknowledged that viruses cause bronchiolitis, but most of the studies focus on RSV. The RSV causes a more severe form of bronchiolitis in children with risk factors including prematurity, cardiovascular disease and immunodeficiency. Other viruses involved in causing bronchiolitis include RV, hMPV, hBoV and co-infections. The RV seems to be associated with a less severe acute disease, but there is a correlation between the early infection and subsequent wheezing bronchitis and asthma in later childhood and adulthood. The supportive therapies used are intravenous fluids and oxygen supplement administered by nasal cannula or CPAP in most complicated patients. Additional pharmacological therapies include epinephrine, 3% hypertonic saline and corticosteroids. The Epinephrine seems to have the greatest short-term benefits and reduces the need of hospital admission, whereas hypertonic saline and corticosteroids seem to reduce the length of hospital stay. As bronchiolitis is such a prevalent disease in children and RV seems to play an important role, perhaps more studies should center around the RV's contribution to the initial disease and following pathology., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Subtle cognitive impairment can be detected in early Parkinson's disease (PD). In a consecutive series of de novo, drug-naive PD patients, we applied stepwise regression analysis to assess which clinical, neuropsychological, and functional neuroimaging (dopamine transporter [DAT] and perfusion single photon emission computed tomography [SPECT]) characteristics at baseline was predictive of cognitive decline during an average follow-up time of about 4 years. Decline both in executive (R(2) = 0.54; p = 0.0001) and visuospatial (R(2) = 0.56; p = 0.0001) functions was predicted by the couple of Unified Parkinson's Disease Rating Scale (UPDRS)-III score and caudate dopamine transporter (DAT) uptake in the less affected hemisphere (LAH). Verbal memory and language decline was predicted instead by caudate DAT uptake and brain perfusion in a posterior parieto-temporal area of the less affected hemisphere (R(2) = 0.42; p = 0.0005). No significant effect was shown for age, baseline neuropsychological scores, and levodopa equivalent dose at follow-up. The combined use of clinical structured examination and brain functional assessment by means of dual single photon emission computed tomography imaging appears as a powerful approach to predict cognitive decline in de novo PD patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Human sleep is considered a global phenomenon, orchestrated by central specialized neuronal networks modulating the whole-brain activity. However, recent studies point to a local regulation of sleep. Sleep disorders, such as sleepwalking, suggest that electroencephalographic (EEG) features of sleep and wakefulness might be simultaneously present in different cerebral regions. Recently, intracranial EEG recording techniques, mainly applied for the presurgical evaluation of drug-resistant epileptic patients, have provided new and interesting information on the activity of different cortical and subcortical structures during sleep in humans. In particular, it has been observed that the thalamus, during the transition between wake and sleep undergoes a deactivation process that precedes the one occurring within the cortex, with extensive cortical territories maintaining an activated pattern for several minutes after the thalamic deactivation. Very recent intracerebral EEG studies have also shown that human NREM sleep can be characterized by the coexistence of wake-like and sleep-like EEG patterns in different cortical areas. Moreover, unit-firing recordings in multiple brain regions of neurosurgical patients evidenced that most sleep slow waves and the underlying active and inactive neuronal states do occur locally. These findings add a new dimension to the concept of local sleep regulation and opens new perspectives in the interpretation of the substrates underlying behavioral states of vigilance. The implications for sleep medicine are also discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A subtle cognitive impairment can be detected early in the course of Parkinson's disease (PD). Executive, memory and visuospatial functions are specifically affected, but the underlying pathophysiological basis is not well elucidated yet and may be heterogeneous. The recent identification of a PD-related cognitive metabolic pattern (PDCP), including hypometabolism in associative frontal, parietal and posterior limbic structures, has integrated the classical notion of a striato-frontal syndrome at the basis of cognitive dys-function. Recent evidence suggests that whilst executive dys-function is seen in virtually all PD patients, visuospatial and memory impairment may share a higher risk for the subsequent development of dementia. By means of perfusion SPECT and [18F]FDG-PET, cortical dys-function may be highlighted since the early stages, it is more evident in PD patients with Mild Cognitive Impairment (MCI), and reaches the maximum in PD dementia (PDD). Posterior temporo-parieto-occipital dys-function in associative and limbic cortex, closely resembling that found in Alzheimer's disease patients, is found in PDD, with a more severe occipital hypometabolism and a relatively milder hypometabolism in medial temporal lobe structures. Furthermore, deficit of acetylcholinesterase (AchE) can be found by means of [11C]MP4A-PET already in early stage of PD, especially in posterior regions, then becoming more severe in PDD and in dementia with Lewy bodies (DLB). Administration of AchE inhibitors to PDD patients increased brain metabolism in bilateral frontal and left parietal regions, and left posterior cingulate. Finally, the recent availability of radiopharmaceuticals able to disclose amyloid brain deposition has allowed to demonstrate amyloid load in a part of patients with PDD, possibly due to diffuse rather than neuritic plaques. Brain PET and SPECT have strongly contributed to the understanding of the pathophysiology of cognitive impairment in PD and may serve as probes to monitor the effects of therapeutic interventions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effectiveness of therapeutic mammoplasty with frozen section in achieving negative surgical margins in a single-stage surgery for breast cancer., Methods: Fifty patients affected by early stage breast cancer treated by therapeutic mammaplasties were retrospectively reviewed in this study. Fifty-two therapeutic mammaplasties were accomplished. After resection the specimen was sent to pathologist for examination with frozen section. Tumour positive margins were defined as presence of cancerous cells at ≤ 2 mm from the edge of the specimen. In case of positive margins a second large re-excision was accomplished intra-operatively. All patients were followed every 4 months for the first 2 years and twice a year subsequently., Results: Fifty-two procedures were evaluated (median follow-up of 72.6 months). The overall survival rate was 98% we had a single case of local recurrent disease (1.9%) that progressed to metastatic disease and patient's death. Frozen section as a diagnostic tool for identification of positive margins has been tested. In conclusion we report a sensitivity of 0.83 and a specificity of 0.93; the predictive positive value was 0.62 and the negative predictive value was 0.97, for a final accuracy of 0.94., Conclusion: Frozen section coupled to oncoplastic resections allows a proper control of local disease and can minimize any second surgical look for margins revision., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We previously showed in female rats that administration of the cannabinoid CB1 receptor antagonist AM251 reduced energy intake by selectively decreasing consumption of a palatable dietary option in comparison to a standard maintenance chow. In the present study we sought to generalize these findings to mice. We presented 6 week old female C57Bl/6J mice with daily 8 h access to a sugar fat whip dietary option along with ad libitum access to moist chow. Mice were injected daily with either vehicle (equal parts polyethylene glycol and saline, 2 ml/kg) or one of three doses of AM251 (1, 3, or 10 mg/kg). Food intake and body weight were measured daily for 21 days. Although 8 h access to sugar fat whip did not induce overconsumption in female mice, AM251 reduced their energy intake and body weight in a dose-dependent manner. The decrease in energy intake occurred for both chow and sugar fat whip. This difference from results in rats suggests that the effect of AM251 on palatable food intake may only be evident in models that induce overconsumption and/or that rats and mice may react differently to CB1 receptor antagonists.

Soy phytoestrogens, among which genistein, seem to protect from breast cancer development. In order to study the role of the breast tumour suppressor BRCA1 in response to genistein, we used a new breast cancer cell model: the SUM1315MO2 cell line carrying the 185delAG BRCA1 mutation, which we stably transfected with a plasmid encoding wild-type BRCA1. We showed that growth of BRCA1 mutant cells was strongly inhibited by genistein whereas it only had a weak effect in cells expressing wild-type BRCA1 protein. BRCA1 mutant cells hypersensitivity could be linked to higher expression of ERbeta gene, which suggests that genistein may be an efficient inhibitor of cancer development in BRCA1 mutant breast cancer cells.

Aim: Long-term oncological follow-up of oncoplastic breast surgery., Methods: Sixthy-one (63 cancers) patients affected by breast cancer suitable for breast conservation, were treated with bilateral breast reductions. Tumours located in the inferior pole of the breast were treated by a superior pedicle technique; lesions in the upper pole or in the infero-lateral or infero-medial quadrants of the breast were removed with an inferior pedicle reduction. Small and medium size breast irrespective of tumour location required a periareolar, or comma-shaped approach., Results: Fifty-six patients were alive at a mean follow-up of 68 months. One patient recurred locally and she is currently alive free of disease., Conclusion: Results from this study are in accordance with those reported by other similar papers. Oncoplastic breast surgery maximizes cosmetic results and with wider excisions provides effective local control.