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The paucity of targeted treatments available in patients with RAS mutant colorectal cancers contributes to the poor prognosis of this patient group compared to those with RAS wild-type disease. Recent liquid biopsy-driven studies have demonstrated that RAS mutant clones might disappear in plasma during the clonal evolution of the disease, opening new unforeseen perspectives for EGFR blockade in these patients. Nevertheless, the lack of detection of RAS mutations in plasma might depend on the low amount of released circulating tumor DNA (ctDNA), making it necessary a more accurate selection of patients with true RAS mutation conversions. In this liquid biopsy-based study, we assessed RAS mutational status in initially RAS-mutant patients at the time of progressive disease from any line of therapy and investigated the incidence of true conversions to plasma RAS wild-type, comparing a colon cancer specific methylation profile with a mutational signature of ctDNA. Globally, considering either mutational panel or methylation profile as reliable tests to confirm or exclude the presence of ctDNA, the percentage of "true RAS converters" was 37.5%. In our series we observed a trend toward a better PFS in patients who received anti-EGFR as second or subsequent treatment lines compared to those who did not.

This paper aims to provide a first glimpse into the genomic characterization of individuals buried in Casal Bertone (Rome, first–third centuries AD) to gain preliminary insight into the genetic makeup of people who lived near a tannery workshop, fullonica. Therefore, we explored the genetic characteristics of individuals who were putatively recruited as fuller workers outside the Roman population. Moreover, we identified the microbial communities associated with humans to detect microbes associated with the unhealthy environment supposed for such a workshop. We examined five individuals from Casal Bertone for ancient DNA analysis through whole-genome sequencing via a shotgun approach. We conducted multiple investigations to unveil the genetic components featured in the samples studied and their associated microbial communities. We generated reliable whole-genome data for three samples surviving the quality controls. The individuals were descendants of people from North African and the Near East, two of the main foci for tannery and dyeing activity in the past. Our evaluation of the microbes associated with the skeletal samples showed microbes growing in soils with waste products used in the tannery process, indicating that people lived, died, and were buried around places where they worked. In that perspective, the results represent the first genomic characterization of fullers from the past. This analysis broadens our knowledge about the presence of multiple ancestries in Imperial Rome, marking a starting point for future data integration as part of interdisciplinary research on human mobility and the bio-cultural characteristics of people employed in dedicated workshops.

Background The availability of fine-grained, culture-specific psychometric outcomes can favor the interpretation of scores of the Montreal Cognitive Assessment (MoCA), the most frequently used instrument to screen for mild cognitive dysfunctions in both instrumental and non-instrumental domains. This study thus aimed at providing: (i) updated, region-specific norms for the Italian MoCA, by also (ii) comparing them to pre-existing ones with higher geographical coverage; (iii) information on sensitivity and discriminative capability at the item level. Methods Five hundred and seventy nine healthy individuals from Northern Italy (208 males, 371 females; age: 63.4 ± 15, 21–96; education: 11.3 ± 4.6, 1–25) were administered the MoCA. Item Response Theory (IRT) was adopted to assess item difficulty and discrimination. Normative values were derived by means of the Equivalent Scores (ESs) method, applied to the MoCA and its sub-scales. Average ESs were also computed. Agreement with previous ESs classification was assessed via Cohen’s k. Results Age and education significantly predicted all MoCA measures except for Orientation, which was related to age only. No sex differences were detected when tested along with age and education. Substantial disagreements with previous ESs classifications were detected. Several items proved to be scarcely sensitive, especially the place item from Orientation and the letter detection task. Memory items showed high discriminative capability, along with certain items assessing executive functions and orientation. Discussion Item-level information herewith provided for the Italian MoCA can help interpret its scores by Italian practitioners. Italian practitioners should consider an adaptive use of region-specific norms for the MoCA.

Background Deficits of executive functioning (EF) are frequently found in neurological disorders. The Frontal Assessment Battery (FAB) is one of the most widespread and psychometrically robust EF screeners in clinical settings. However, in Italy, FAB norms date back to 15 years ago; moreover, its validity against “EF-loaded” global cognitive screeners (e.g., the Montreal Cognitive Assessment, MoCA) has yet to be tested. This study thus aimed at (a) providing updated normative data for the Italian FAB and (b) assessing its convergent validity with the MoCA. Methods Four-hundred and seventy-five healthy Italian native speakers (306 females, 169 males; mean age: 61.08 ± 15.1; mean education: 11.67 ± 4.57) were administered by the MoCA and the FAB. FAB items were divided into three subscales: FAB-1 (linguistically mediated EF), FAB-2 (planning), and FAB-3 (inhibition). Regression-based norms were derived (equivalent scores) for all FAB measures. Results Age and education were predictive of all FAB measures, whereas no gender differences were detected. The FAB and its sub-scales were related to MoCA measures—the strongest associations being found with MoCA total and MoCA-EF scores. FAB sub-scales were both internally related and associated with FAB total scores. Discussion The FAB proved to have convergent validity with both global cognitive and EF measures in healthy individuals. The present study provides updated normative data for the FAB and its sub-scales in an Italian population sample, and thus supports an adaptive usage of this EF screener.

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

Background Several studies have raised the issue of the inadequacy of CellSearch® to detect the entire pool of circulating tumor cells (CTCs) from blood of cancer patients, suggesting that cells expressing low levels of epithelial cell adhesion molecule (EpCAM) are not recognized by the capture reagent. In this exploratory study, we aimed to evaluate the status of EpCAM in CTCs isolated from a group of metastatic colorectal cancer patients, in 40% of whom, CTC had been found to be undetected by the CellSearch® system. Methods CTCs were analyzed using both a microfiltration method (ScreenCell) and CellSearch® in parallel. Furthermore, since EpCAM exists in 2 different variants, we investigated the presence of both its intracellular domain (EpICD) and extracellular domain (EpEX) through immunofluorescence staining of CTCs on filters. Results Results from immunofluorescence experiments demonstrated that, overall, EpICD and/or EpEX was expressed in 176 CTCs detected by ScreenCell, while the CellSearch® system was able to capture only 10 CTCs. Conclusions This is the first demonstration that the low sensitivity of CellSearch® to detect CTCs in colorectal cancer patients is not due to the lack of EpCAM.

How we make decisions that have direct consequences for ourselves and others forms the moral foundation of our society. Whereas economic theory contends that humans aim at maximizing their own gains, recent seminal psychological work suggests that our behavior is instead hyperaltruistic: We are more willing to sacrifice gains to spare others from harm than to spare ourselves from harm. To investigate how such egoistic and hyperaltruistic tendencies influence moral decision making, we investigated trade-off decisions combining monetary rewards and painful electric shocks, administered to the participants themselves or an anonymous other. Whereas we replicated the notion of hyperaltruism (i.e., the willingness to forego reward to spare others from harm), we observed strongly egoistic tendencies in participants’ unwillingness to harm themselves for others’ benefit. The moral principle guiding intersubject trade-off decision making observed in our study is best described as egoistically biased altruism, with important implications for our understanding of economic and social interactions in our society. US Army Research Office

Background and aim of the work: Bioethics is relevant in healthcare and medical schools. However, unlike other foreign countries, its teaching in Italy has only been recently introduced, it is less extensively offered and no academic standards for bioethics education have been established. This research aims at understanding whether university bioethics courses attendees appreciate and consider teaching strategies to be effective with the objective of validating a coherent didactic approach to the discipline and stimulate further discussion on ways to improve it. Methods: A standardized survey was administered to 1590 students attending undergraduate degree programs in medicine and healthcare at four Italian universities. Results: The majorityof interviewees (92.5%) had an interest in bioethics, considered it to be important for any life-sciences-related program (73.5%) and most healthcare (77.2%) and medical students (69.2%) suggested its teaching should be included in their curricula and made mandatory (66.3%) and continuous (57.7%), given its usefulness in clinical practice. Students consider bioethics as a care-integrated practice and appreciate teaching methods where it is integrated into clinical cases. Conceptual specificity and interdisciplinarity may affect the learning process and contribute to enhance students’ analytical skills. Conclusions: Italian bioethics education should be revised to meet students’ expectations and preferences. Its complex, multi-disciplinary and transversal nature suggests bioethical education to be flexible and integrated among different disciplines, thus stimulating a broader critical capacity through cases studies and other interactive teaching methods for helping students better deal with bioethics-inherent difficulties and improve the learning process. (www.actabiomedica.it)

Anatomical ex-votos of feet have always been interpreted as representing the unhealthy part of the body for which patients were asking healing. However, according to the archaeological data and literary sources, another interpretation is also possible: the purpose of this article is to focus on the strong relationship between feet and fertility in the ancient world by cross-referencing the available archaeological evidence with the scientific data relating to this topic. That shed light on an important aspect of the Healing Temples in Greek and Roman medicine.

Background Clinical behavior of non-muscle-invasive bladder cancer (NMIBC) is largely unpredictable, and even patients treated according to European Association of Urology recommendations have a heterogeneous prognosis. High-grade T1 (HGT1) bladder cancer is the highest-risk subtype of NMIBC, with an almost 40% rate of recurrence and 20% of progression at 5 years. Nomograms predicting risk of recurrence, progression, and cancer-specific survival (CSS) are not available specifically within HGT1 bladder cancer, and the identification of robust prognostic biomarkers to better guide therapeutic strategies in this subgroup of patients is of paramount importance. Strategies to identify putative biomarkers in liquid biopsies from blood and urine collected from patients with bladder cancer have been intensively studied in the last few years. Subjects, Materials, and Methods We here report the final analysis of a single-center prospective study aimed to investigate the impact of circulating tumor cells (CTCs) on CSS and overall survival (OS) in 102 patients with HGT1 bladder cancer, in a median follow-up of 63 months. Results We here demonstrate that the presence of even a single CTC is predictive of shorter CSS and OS, as compared with the standard predictive variables. Points of attention in this multivariable analysis are the long-term follow-up and the adequate number of outcome events. Conclusion The accurate risk stratification provided by CTCs might be essential for determining the best surveillance strategy for patients after diagnosis. A closer follow-up, an early radical surgery, or even a systemic treatment might be recommended in patients with super-high-risk non-muscle-invasive bladder cancer.

5-aminosalicylic acid (5-ASA) is the most widely used drug for the treatment of ulcerative colitis. The benefits of targeted delivery of 5-ASA to the large intestine are well known, resulting in reduced systemic absorption and increased local concentrations at the disease site. In the present study, a 5-ASA colon delivery system based on the time-dependent strategy, exploiting the relatively consistent small intestinal transit time (SITT), was manufactured and evaluated in vitro as well as in vivo. The system was obtained by successive spray-coating of an immediate-release tablet core with low-viscosity HPMC and Eudragit® L. The enteric film was effective in preventing release during the acidic stage of the in vitro test, while the HPMC coating brought about reproducible lag phases prior to release in phosphate buffer medium. A γ-scintigraphy investigation pointed out that, following administration to fasted and fed volunteers, disintegration of the units never occurred prior to colon arrival. In all cases, a lag time preceded the appearance of the drug and its N-acetyl metabolite in the bloodstream, which was found to correlate with the time of disintegration in a linear mode. The plasma levels of the drug and metabolite as well as their cumulative urinary recovery were relatively low with respect to those reported when 5-ASA is delivered to the small bowel.

Purpose Italy has long lacked a law regulating patients' informed consent and advance directives (ADs). All previous attempts to introduce a law on this matter failed to reach positive outcomes, and aroused heated ideological debate over the exact meaning of life and death. We report on the new law on informed consent and ADs approved by the Italian Parliament on 14th December 2017. Materials and methods We analyse the new law and discuss the main ethical points connected with it, in the Italian context and in comparison with the international situation. Results The law provides for fundamental ethical principles and important guidelines: respect for patients' self-determination in all phases of life, option to refuse or interrupt life-sustaining treatments, including artificial nutrition and hydration, the legitimacy of end-of-life decisions, and the implementation of palliative care to ease suffering and pain. Conclusions The effects of the new law must be tested in the field. Its objectives will be achieved if, in clinical practice, ADs are able to satisfactorily represent informed personal preferences through patients' relationships with their physicians, as part of personalized advance care planning. Future studies are necessary to assess the impact of the new law in Italy.

This study aimed to investigate whether pulmonary shunt grade on transthoracic contrast echocardiography (TTCE) predicts the size of pulmonary arteriovenous malformations (PAVMs) on chest computed tomography (CT) and subsequent feasibility for transcatheter embolotherapy. We prospectively included 772 persons with possible or definite hereditary haemorrhagic telangiectasia, who underwent both TTCE and chest CT for screening of PAVMs. A quantitative three-point grading scale was used to classify the pulmonary shunt size on TTCE (grade 1-3). Transcatheter embolotherapy was performed for PAVMs deemed large enough for endovascular closure on chest CT. TTCE documented pulmonary shunting in 510 (66.1%) patients. The positive predictive value of a pulmonary shunt grade 1, 2 and 3 on TTCE for presence of PAVMs on chest CT was 13.4%, 45.3% and 92.5%, respectively (p

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality. © 2007 The Authors.

Identification of factors that predict recurrent antisocial behavior is integral to the social sciences, criminal justice procedures, and the effective treatment of high-risk individuals. Here we show that error-related brain activity elicited during performance of an inhibitory task prospectively predicted subsequent rearrest among adult offenders within 4 y of release ( N = 96). The odds that an offender with relatively low anterior cingulate activity would be rearrested were approximately double that of an offender with high activity in this region, holding constant other observed risk factors. These results suggest a potential neurocognitive biomarker for persistent antisocial behavior.

We have initially shown that DC/ApoNec vaccine can induce protection against the poorly immunogenic B16F1 melanoma in mice. The population of DC obtained for vaccination after 7days culture with murine GM-CSF is heterogeneous and presents about 60% of CD11c+ DC. Therefore, our purpose was to identify the phenotype of the cells obtained after differentiation and its immunogenicity once injected. DC were separated with anti-CD11c microbeads and the two populations identified in terms of CD11c positivity (DC+ and DC-) were also studied. Approximately 26.6% of the cells in DC+ fraction co-expressed CD11c+ and F4/80 markers and 75.4% were double positive for CD11c and CD11b markers. DC+ fraction also expressed Ly6G. DC- fraction was richer in CD11c-/F4/80+ macrophages (44.7%), some of which co-expressed Ly6G (41.8%), and F4/80-/Ly6-G+ neutrophils (34.6%). Both DC+ and DC- fractions displayed similar capacity to phagocyte and endocyte antigens and even expressed levels of MHC Class II and CD80, CD83 and CD86 costimulatory molecules similar to those in the DC fraction. However, only DC/ApoNec vaccine was capable to induce protection in mice (p

To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.

A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2 h of testing in 0.1 N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4 °C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6 h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds.

Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape.

A 64-y-old man presented to Medical Oncology Department a metastatic invasive ductal breast carcinoma, positive for estrogen (ER) and progesterone receptors (PR) and Her2/neu negative. The patient was treated with different lines of therapy, with rapid radiological progression of disease. After four courses of a third-line chemotherapy, a radiological stable disease was maintained. The patient was followed by serial blood drawings for the characterization and count of circulating tumor cells (CTC). This is the first report concerning the predictive and prognostic value of CTC in a male breast cancer patient.

Background Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality. Aim This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients. Methods We analyzed 16 years of surveillance data from a tertiary hereditary hemorrhagic telangiectasia referral center in Italy. We considered for inclusion in this study 502 consecutive Italian patients at risk of hereditary hemorrhagic telangiectasia who presented at the hereditary hemorrhagic telangiectasia referral center and underwent a multidisciplinary screening protocol for the diagnosis of hereditary hemorrhagic telangiectasia. Of the 502 individuals assessed in the center, 154 had hepatic vascular malformations and were the subject of the study; 198 patients with hereditary hemorrhagic telangiectasia and without hepatic vascular malformations were the controls. Additionally, we report the response to treatment of patients with complicated hepatic vascular malformations. Results The 154 patients were included and followed for a median period of 44 months (range 12–181); of these, eight (5.2%) died from VM-related complications and 39 (25.3%) experienced complications. The average incidence rates of death and complications were 1.1 and 3.6 per 100 person-years, respectively. The median overall survival and event-free survival after diagnosis were 175 and 90 months, respectively. The rate of complete response to therapy was 63%. Conclusions This study shows that substantial morbidity and mortality are associated with liver vascular malformations in hereditary hemorrhagic telangiectasia patients.

In the last years the nature of initiating melanoma cells has been discussed and the melanoma stem cell theory has been proposed as and alternative and/or supplemental view of newborning melanoma cells. It has been described that melanoma cells derived from metastatic melanoma specimens as well as melanoma cell lines are able to grow in an embryonic stem cell-based media and these melanoma stem-like cells possess capacity of self-renewal and high tumorigenicity. In 2005 the first evidence of a stem-cell like population existence in human melanoma has been provided. CD133 or prominin-1 is one of most studied marker of staminality expressed by melanoma cells; specifically, the down regulation of CD133 leads to a reduced cell capacity to metastatize. Nevertheless, there is disagreement concerning the constant presence of CD133þ cells in primary and metastatic melanomas. ABCB5, the third member of the human P-gp family, is a rhodamine and doxorubicin efflux transporter, identified as a novel drug transporter involved in drugresistance in human malignant melanoma. ABCB5 was found to be specifically expressed on CD133þ tumor

The corpus callosum is the largest white matter pathway in the human brain. The most posterior portion, known as the splenium, is critical for interhemispheric communication between visual areas. The current study employed diffusion tensor imaging to delineate the complete cortical projection topography of the human splenium. Homotopic and heterotopic connections were revealed between the splenium and the posterior visual areas, including the occipital and the posterior parietal cortices. In nearly one third of participants, there were homotopic connections between the primary visual cortices, suggesting interindividual differences in splenial connectivity. There were also more instances of connections with the right hemisphere, indicating a hemispheric asymmetry in interhemispheric connectivity within the splenium. Combined, these findings demonstrate unique aspects of human interhemispheric connectivity and provide anatomical bases for hemispheric asymmetries in visual processing and a long-described hemispheric asymmetry in speed of interhemispheric communication for visual information.

Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) were combined to examine the relationship between callosal organization and cortical activity across hemispheres. Healthy young adults performed an incidental verbal encoding task (semantic judgments on words) while undergoing fMRI. Consistent with previous studies, the verbal encoding task was associated with left-lateralized activity in the inferior prefrontal cortex (LIPFC). When subjects were divided into two groups based on fractional anisotropy (FA) values in the anterior corpus callosum (DTI), individuals with low anterior callosal FA were found to exhibit greater activity in a homologous region within the right inferior prefrontal cortex (RIPFC) relative to those with high anterior callosal FA. Interestingly, whereas the magnitude of RIPFC activity did not negatively impact subsequent verbal memory performance for individuals with low anterior callosal FA, greater RIPFC activity during verbal encoding was associated with poorer subsequent memory performance for individuals with high anterior callosal FA. Together, these findings provide novel evidence that individual differences in callosal organization are related to the extent of nondominant cortical activity during performance during a lateralized task, and further, that this relationship has consequences on behavior.

The metastatic lymph node 64 (MLN64), which is localized in the human chromosome 17, encodes a protein with strong homology with steroidogenic acute regulatory protein. Its overexpression in human breast carcinomas and MLNs led to the hypothesis that this protein could be involved in intraneoplastic steroidogenesis. In the present study, we investigated the expression of MLN64 in prostate cancer, another hormone-dependent tumor, and compared its expression with that of CYP17, the gene encoding for the key enzyme of androgen synthesis. We investigated by RT-PCR the expression of MLN64 and CYP17 in 60 prostatic tumors and compared their expression with the stage of disease and the appearance of relapses in a follow-up of 24 months. We found MLN64 and CYP17 expressed in all samples examined, with significantly higher expression in neoplastic tissues with respect to normal tissues (NTs). Moreover, only in neoplastic but not in NTs, a positive linear correlation was found between MLN64 and CYP17 gene expression. MLN64 and CYP17 expression seems to correlate with high stage, high Gleason score and short relapse-free time. These data, for the first time, demonstrate the presence of MLN64 and CYP17 expression in both normal and neoplastic prostatic tissues. The biological role of MLN64 in human prostate and, particularly, in neoplastic tissue is still unclear. Our findings concerning MLN64 and CYP17 gene expression and their significant positive correlation in human prostate cancer may suggest their possible role in intraneoplastic autonomous steroidogenesis.

The purpose of the study was to investigate simple calculation in the two cerebral hemispheres of a split-brain patient. In a series of four experiments, the left hemisphere was superior to the right in simple calculation, confirming the previously reported left hemisphere specialization for calculation. In two different recognition paradigms, right hemisphere performance was at chance for all arithmetic operations, with the exception of subtraction in a two-alternative forced choice paradigm (performance was at chance when the lure differed from the correct answer by a magnitude of 1 but above chance when the magnitude difference was 4). In a recall paradigm, the right hemisphere performed above chance for both addition and subtraction, but performed at chance levels for multiplication and division. The error patterns in that experiment suggested that for subtraction and addition, the right hemisphere does have some capacity for approximating the solution even when it is unable to generate the exact solution. Furthermore, right hemisphere accuracy in addition and subtraction was higher for problems with small operands than with large operands. An additional experiment assessed approximate and exact addition in the two hemispheres for problems with small and large operands. The left hemisphere was equally accurate in both tasks but the right hemisphere was more accurate in approximate addition than in exact addition. In exact addition, right hemisphere accuracy was higher for problems with small operands than large, but the opposite pattern was found for approximate addition.

Purpose To present rectal toxicity rates in patients administered a polyethylene glycol (PEG) hydrogel rectal spacer in conjunction with combination high-dose-rate brachytherapy and external beam radiotherapy. Methods and Materials Between February 2010 and April 2015, 326 prostate carcinoma patients underwent combination high-dose-rate brachytherapy of 16 Gy (average dose 15.5 Gy; standard deviation [SD] = 1.6 Gy) and external beam radiotherapy of 59.4 Gy (average dose 60.2 Gy; SD = 2.9 Gy). In conjunction with the radiation therapy regimen, each patient was injected with 10 mL of a PEG hydrogel in the anterior perirectal fat space. The injectable spacer (rectal spacer) creates a gap between the prostate and the rectum. The rectum is displaced from the radiation field, and rectal dose is substantially reduced. The goal is a reduction in rectal radiation toxicity. Clinical efficacy was determined by measuring acute and chronic rectal toxicity using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. Results Median followup was 16 months. The mean anterior–posterior separation achieved was 1.6 cm (SD = 0.4 cm). Rates of acute Grade 1 and 2 rectal toxicity were 37.4% and 2.8%, respectively. There were no acute Grade 3/4 toxicities. Rates of late Grade 1, 2, and 3 rectal toxicity were 12.7%, 1.4%, and 0.7%, respectively. There were no late Grade 4 toxicities. Conclusions PEG rectal spacer implantation is safe and well tolerated. Acute and chronic rectal toxicities are low despite aggressive dose escalation.

Motor-related regions of parietal and prefrontal cortices have been shown to selectively activate when observers passively view objects that afford manual grasping. Yet, it remains unknown whether these cortical responses depend on prior motor-related experience with the object being observed. To address this question, we asked participants to undergo fMRI scanning while viewing exemplars of two different categories of graspable objects: one associated with extensive motor experience (door knobs) and one associated with no self-reported motor experience (artificial rock climbing holds). Despite participants' lack of experience grasping climbing holds, these objects were found to generate a systematic response in several visuomotor-related regions of cortex-including left PMv and left AIP. Interestingly, however, the response to door knobs did not include activity in any motor-related regions, being limited instead to a comparatively small bilateral area of lateral occipital cortex, relative to the more spatially extensive response in occipital and temporal cortex that was observed for climbing holds. This result suggested that object-specific responses in both visual- and motor-related cortex may in fact negatively correlate with object-specific motor experience. To test this possibility, we repeated the experiment using participants having extensive self-reported experience grasping climbing holds (i.e., veteran indoor rock climbers). Consistent with our hypothesis, both climbing holds and door knobs generated activity limited to lateral occipital cortex. Taken together, these data support the proposal that repeated real-world motor experience with an object category may lead to reduced implicit analysis in both motor- and visual-related regions of cortex.

Functional magnetic resonance imaging (fMRI) was used to examine the neural correlates of perceptual causality. Participants were imaged while viewing alternating blocks of causal events in which a ball collides with, and causes movement of another ball, versus non-causal events in which a spatial or a temporal gap precedes the movement of a second ball. There were significantly higher levels of relative activation in the right middle frontal gyrus and the right inferior parietal lobule for causal relative to non-causal events. Furthermore, when the differential effects of spatial and temporal incontiguities were subtracted from the contiguous stimuli, we observed both common (right prefrontal) and unique (right parietal and right temporal) regions of activation as a function of spatial and temporal processing of contiguity, respectively. Taken together, these data provide a means to help determine how the visual system extracts causality from dynamic visual information in the environment using spatial and temporal cues.

Visual spatial attention has long been associated with facilitatory effects on visual perception. Here, we report that spatial attention can also modulate implicit visuomotor processing in dorsal regions of human cortex. Participants underwent fMRI scanning while performing a voluntary attentional orienting task that varied the category of a task-irrelevant object in the attended location (tool vs. non-tool). Data were then analyzed as a function of the attended location (left vs. right visual field) and the object category in that location. We found that the fMRI BOLD response in two visuomotor-related regions--the supplementary motor area (SMA) and the left inferior parietal lobule (IPL)--showed an interaction between the location of attention and the location of the tool in the bilateral display. Further, these responses were statistically distinct from those regions in dorsal cortex showing activity modulated only by the tool location or only by the attended location. While the effects of attending non-foveally within the visual field have been well documented in relation to visual perception, our findings support the proposal that voluntary visuospatial attention may also have consequences for the implicit planning of object-directed actions.

Neuroimaging and lesion studies have provided insights into the neural mechanisms underlying numerical processing, yet the roles of the right and left hemispheres have not been systematically investigated within a single study. To address this issue, we investigated subitizing and magnitude comparison abilities in a split-brain patient. The first experiment examined the two hemispheres' abilities to enumerate briefly presented sets of one to four stimuli. Both hemispheres were equally able to perform this task. The second and third experiments examined the hemispheres' abilities to make magnitude judgments about two simultaneously presented stimuli that were either identically coded (i.e., two Arabic numerals, two number words, or two arrays of dots) or differently coded (e.g., an Arabic numeral and a number word). Although the left hemisphere was more accurate than the right when the task involved number words, both hemispheres were able to make comparisons between numerical representations regardless of stimuli coding. In addition, both hemispheres exhibited a distance effect. The results are discussed in the context of Dehaene's triple-code model.

To evaluate the incidence of retinal detachment (RD) after cataract surgery performed by phacoemulsification in very highly myopic eyes.Retrospective, paired-eye, case-control trial.We assessed the development of RD in 930 eyes from 930 subjects (mean age = 62.5 +/- 8.5 years) affected by very high myopia (between -15 and -30 diopters) undergoing cataract surgery after uncomplicated phacoemulsification (cataract-subjected [CS] eyes). Fellow eyes served as controls. Follow-up was 36 months.Detachment of the retina.Retinal detachment was observed in 8.0% of CS eyes compared with 1.2% of control eyes (P0.01, chi-square test). In CS eyes, posterior RD was most common (52.7% of eyes with RD). In control eyes, peripheral detachments with or without macular involvement were most common (47.3% of eyes with RD).Cataract surgery, despite the use of a safe technique such as phacoemulsification, increases the risk of RD development in very highly myopic eyes.

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients. Patients and Methods: Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level. Results: We found a significant correlation (P < .005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients. Conclusion: Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.

SummaryPlatelet activation, commonly found in lung cancer patients, may cause the release of angiogenic factors, such as vascular endothelial growth factor (VEGF-A). The present study was designed to investigate whether plasma VEGF-A levels were associated to different stages of non-small cell lung cancer (NSCLC). Moreover, sP-selectin, prothrombin fragment 1+2 (F1+2),thrombin-antithrombin III complex (TATc) and D-dimer levels were measured to test the hypothesis of an involvement of platelet and coagulation activation in tumor angiogenesis. VEGF-A, sP-selectin, F1+2, TATc and D-dimer levels were elevated in 65 patients with NSCLC, particularly in metastatic patients. sP-selectin (p

Objectives: To analyse the behaviour of pre-surgical serum levels of soluble (s)E-selectin and vascular cell adhesion molecule (sVCAM) in patients with colorectal cancer, and to evaluate their possible correlation with carcinoembryonic antigen (CEA), pro-inflammatory cytokines and clinicopathological features with respect to their prognostic value in predicting metastatic disease. Methods: Pre-surgical serum levels of sE-selectin, sVCAM, interleukin-6 (IL-6), IL-1β, tumour necrosis factor-α (TNF-α) and CEA were measured in 194 patients with colorectal adenocarcinoma, 40 patients with benign colorectal diseases and 59 healthy subjects. Results: sE-selectin, sVCAM, TNF-α and IL-6 levels were significantly higher in patients with colorectal cancer compared to either healthy subjects or patients with benign disease. Positive rates of sE-selectin, sVCAM and TNF-α levels were significantly associated with Dukes’ stage D colorectal cancer, and all three variables were independently associated to the presence of distant metastases. Positive sE-selectin, sVCAM and TNF-α levels were significantly associated to CEA. TNF-α and CEA levels were independently related to the presence of positive levels of sE-selectin and/or sVCAM. Conclusions: Our findings suggest that the host inflammatory response to cancer cells, and/or their released products (i.e. CEA), might be responsible (via cytokine release) for the elevation in circulating adhesion molecules in patients with colorectal cancer.

Converging evidence suggests that temporal representations of brief durations are derived subcortically. We tested split-brain patient JW in order to investigate whether these representations project bilaterally or unilaterally to cortex. Using visual stimuli to signal time intervals, JW was asked to compare the duration of a pair of standard stimuli that were presented bilaterally with a comparison stimulus that was presented to either the left or right visual field. Assuming the hand of response is controlled by the contralateral cerebral hemisphere, a hand by visual field interaction was predicted if the representation of stimulus duration was restricted to the cerebral hemisphere receiving the lateralized stimulus. However, we failed to observe this interaction for two different ranges of stimulus durations, both in the hundred (Experiment 2) to hundreds (Experiment 1) of milliseconds range. Instead, there was a consistent right hemisphere advantage in task performance. When the task then required a discrimination based on the physical size of the stimuli rather than their duration, an interaction between response hand and visual field was obtained (Experiment 3). Taken together, these results suggest that (1) even though the comparison stimulus was presented unilaterally, the representation of its duration was available to both cerebral hemispheres, and (2) a right hemisphere advantage in psychophysical tasks requiring the comparison of successive stimuli is observed for temporal and non-temporal judgments.

The localization of brain functions using neuroimaging techniques is commonly dependent on statistical analyses of groups of subjects in order to identify sites of activation, particularly in studies of episodic memory. Exclusive reliance on group analysis may be to the detriment of understanding the true underlying cognitive nature of brain activations. In the present study, we found that the patterns of brain activity associated with episodic retrieval are very distinct for individual subjects from the patterns of brain activity at the group level. These differences go beyond the relatively small variations due to cyctoarchitectonic differences or spatial normalization. We quantify this individual variability by cross-correlating volumes of brain images. We demonstrate that individual patterns of brain activity are reliable over time despite their extensive variability. We suggest that varied but reliable individual patterns of significant brain activity may be indicative of different cognitive strategies used to produce a recognition response. We believe that individual analysis in conjunction with group analysis may be critical to fully understanding the relationship between retrieval processes and underlying brain regions.

While it is commonly noted that the right cerebral hemisphere is specialized for visuospatial processing, the scope and nature of this specialization remain somewhat ill defined. Our previous research with callosotomy ('split-brain') patients has suggested that the asymmetry may be limited to conditions that have an explicit spatial component. To investigate this we compared the performance of the divided hemispheres of two callosotomy patients on four simple visual-matching tasks. These tasks were orientation discrimination, vernier offset discrimination, size discrimination, and luminance discrimination. In each task, two stimuli were presented briefly to one visual hemifield and the patient was asked to discriminate whether they were the same or different. The first three tasks (orientation, vernier, and size) were all spatial in nature and were performed better by the right hemisphere. The luminance discrimination task, which is non-spatial, was performed equivalently by the two hemispheres. These results support the view that the fundamental difference in visual function between the hemispheres is in the ability to perform spatial discriminations.

Objective: Psychopathy is a personality disorder with symptoms that include lack of empathy or remorse, antisocial behavior, and excessive self-focus. Previous neuroimaging studies have linked psychopathy to dysfunction in the default mode network (DMN), a brain network that deactivates during externally focused tasks and is more engaged during self-referential processing. Specifically, the DMN has been found to remain relatively active in individuals with psychopathic tendencies during externally focused tasks, suggesting a failure to properly deactivate. However, the exact extent and nature of task-induced DMN dysfunction is poorly understood, including (a) the degree to which specific DMN subregions are affected in criminal psychopaths, and (b) how activity in these subregions relates to affective/ interpersonal and antisocial/lifestyle traits of psychopathy. Method: We performed a group independent component analysis to assess DMN activation during a Go/NoGo task in a group of 22 high-psychopathy and 22 low-psychopathy prisoners. The identified group-level DMN was parcellated into 6 subregions, and group differences in task-induced activity were examined. Results: In general, DMN subregions failed to deactivate beneath baseline in the high-psychopathy group. A group comparison with the low-psychopathy group localized this attenuated task-induced deactivation to the posteromedial cortical (mPC) region of the DMN. Moreover, multiple regression analyses revealed that activity in the mPC was associated with affective/interpersonal traits of psychopathy. Conclusion: These findings suggest that attenuated deactivation of the mPC subregion of the DMN is intrinsic to psychopathy, and is a pattern that may be more associated with affective psychopathic traits, including lack of concern for others.

Factors that determine early atherosclerotic lesions are unknown, but the vascular extracellular matrix (ECM) appears to be involved. Two hypotheses, which directly or indirectly reflect ECM involvement, have been proposed to explain the early molecular events of this pathology. The first hypothesis is the response-to-retention hypothesis, which emphasizes that the interaction between ECM molecules, particularly proteoglycans (PGs) and lipoproteins, is the key event in early atherogenesis (Williams & Tabas 1995; Camejo et al. 1998; Skalen et al. 2002). The second hypothesis is the chronic inflammation hypothesis (Ross 1999; Tedgui & Mallat 2006), in which the binding of cytokines and growth factors to ECM PGs may increase the residence time of these molecules in the extracellular environment and modulate their functional activity dynamically (Camejo et al. 1995; Young & Murphy-Ullrich 2004; Groeneveld et al. 2005). Consequently, the expression and distribution of arterial PGs are significantly modulated during atherosclerosis and ageing (Tovar et al. 1998). For instance, human atherosclerosis-prone arteries express PGs, such as biglycan and decorin, in the outer layer of the intima of prelesional areas preceding lipid deposition (Nakashima et al. 2007). Besides, GAG chains attached to the protein core of PGs undergo specific structural modifications during the development of the disease. Elongated GAG chains have been reported in human early atherosclerotic lesions (Theocharis et al. 2002; Little et al. 2007). For instance, hyperelongated chondroitin sulphate (CS) chains of biglycan may be the key factor for atherosclerosis, because they enhance the low-density lipoprotein (LDL) binding affinity (Anggraeni et al. 2011). As it is known, hypercholesterolaemia is a dominant risk factor for atherosclerosis. Cholesterol feeding has been used to increase serum cholesterol levels and then to assess hypercholesterolaemia-related metabolic disturbances in different animal models (Deepa & Varalakshmi 2005; Hachani et al. 2011; Raman et al. 2011). In contrast to that observed in humans, in rats, hypercholesterolaemia alone is unable to induce intimal thickening and atheroma plaque development, mainly as a consequence of the lack of cholesteryl ester transfer protein (CETP) (Hogarth et al. 2003; Hachani et al. 2010). The aim of this study was to analyse quantitative and structural modifications of PGs in aortas isolated from rats upon treatment with a high-cholesterol diet, to understand whether vascular wall remodelling may protect against the atheroma lesions.

The hypothesis of the “liquid biopsy” using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity.

High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

Between January 1979 and September 1999 a series of 96 patients were operated on at our institution for iatrogenic biliary injuries, and among them 62 involved the proximal biliary tract. Injuries, according to the Strasberg classification, were type E2 in 18 patients, type E3 in 29 patients, and type E4 in 15 patients. The most frequent primary surgical procedures were laparoscopic cholecystectomy in 27 of the 62 patients (43.6%) and open cholecystectomy in 30 patients (48.3%). Previous repair had been attempted in 25 patients (40.3%). A total of 58 cholangiojejunostomies were performed. Repair had been performed directly, and a T-tube had been left in the main bile duct in four patients with E2 Strasberg lesions. Postoperative death occurred in four patients (6.4%). Outcome was graded as excellent, good, or poor depending on clinical symptoms, liver function tests, and the need for reintervention due to anastomotic stricture. The final outcome was evaluated in 54 patients. The mean follow-up was 5.9 +/- 0.3 years, with the longest follow-up 10.2 years. Following our first repair 49 of the 54 patients (90.7%) had excellent results, 1 (1.9%) had good results, and 4 (7.4%) had poor results. None of the patients who underwent immediate or early repair had complications. Diagnostic and therapeutic courses are given on the basis of the type of lesion and the timing of repair. We emphasize the importance of timing (i.e., carrying out surgical repair as soon as possible) and of cholangiojejunostomy reconstruction in respect to defined technical principles. Moreover, we believe that repair treatment at a hepatobiliary center with multidisciplinary competence greatly influences the final long-term outcome.

Identification of visually presented objects and words is facilitated by implicit memory for past visual experiences with those items. Several behavioral and neuroimaging studies suggest that this form of memory is dependent on perceptual processes localized in the right occipital lobe. We tested this claim by examining implicit mem- ory in patients with extensive right occipital lobe lesions, using lexi- cal-decision, mirror-reading, picture-fragment, and word-fragment- completion tests, and found that these patients exhibited normal levels of priming. We also examined implicit memory in patients with com- plete callosotomies, using standard and divided-visual-field word- fragment-completion procedures, and found that the isolated left hemisphere exhibited normal priming effects. The results indicate that the right occipital lobe does not play a necessary role in visual im- plicit memory, and that the isolated left hemisphere can support nor- mal levels of visual priming in a variety of tasks. In order to determine how the brain utilizes information about past events, it is necessary to identify the brain regions that are involved in different memory processes. The examination of patients with local- ized brain damage has played a critical role in identifying the neuro- logical substrates of several memory processes (e.g., Gabrieli, 1998; Squire, 1988). For example, patients with damage to the medial tem- poral lobes exhibit pronounced deficits in explicit tests of memory, such as free recall, that require conscious recollection of previous epi- sodes (e.g., Cohen & Squire, 1980; Scoville & Milner, 1957). This in- dicates that the medial temporal lobes play a necessary role in this form of memory. These same patients perform normally on other tasks, such as tests of visual implicit memory, in which a person's ability to identify or make judgments about visually presented items is primed, or enhanced, by previous visual encounters with those items (e.g., Graf & Mandler, 1984; Warrington & Weiskrantz, 1974). The preserved priming observed in these patients indicates that the medial temporal lobes are not necessary for normal visual implicit memory. The precise neuroanatomical substrates of visual implicit memory are unknown. However, studies of brain-damaged patients and neu- roimaging studies of healthy subjects show that the occipital lobes are involved in this form of memory, and several of these studies suggest that the right hemisphere may be particularly important. For example, a number of patients with occipital lobe lesions have been shown to exhibit deficits on visual implicit memory tasks (Carlesimo, Fadda, Sabbadini, & Caltagirone, 1994; Curran, Schachter, & Galluccio

Recent research has demonstrated that memory for words elicits left hemisphere activation, faces right hemisphere activation, and nameable objects bilateral activation. This pattern of results was attributed to dual coding of information, with the left hemisphere employing a verbal code and the right a nonverbal code. Nameable objects can be encoded either verbally or nonverbally and this accounts for their bilateral activation. We investigated this hypothesis in a callosotomy patient. Consistent with dual coding, the left hemisphere was superior to the right in memory for words, whereas the right was superior for faces. Contrary to prediction, performance on nameable pictures was not equivalent in the two hemispheres, but rather resulted in a right hemisphere superiority. In addition, memory for pictures was significantly better than for either words or faces. These findings suggest that the dual code hypothesis is an oversimplification of the processing capabilities of the two hemispheres.

What roles are played by the cerebral hemispheres in planning object-oriented reaching and grasping movements? In an attempt to address this question, we compared the abilities of the left and right hemispheres of commissurotomy patient J.W. to imagine hand manipulation (i.e., grasp) or arm transportation (i.e., reach) movements. A graphically rendered manipulandum (dowel) was briefly presented to the left (LVF) or right (RVF) visual fields in a variety of different orientations. In the grasp selection task (experiment 1), J.W. was required to determine which side of a dowel his thumb would be on if he were to engage the stimulus in a power grip using either his dominant (right) or non-dominant hand. In the reach selection task (experiment 3), J.W. judged which end his elbow would be on if he treated the dowel as an armrest for his dominant or non-dominant forearm. No actual movements were allowed in either task. Movements selected in the imagery tasks were compared with those chosen during actual motor control under comparable circumstances. These comparisons revealed a left hemisphere advantage for representing grasping movements involving the right hand, and reaching movements involving the left arm. The right hemisphere, by contrast, displayed moderate accuracy when representing grasping movements with the left hand, but appeared incapable of imagining reaching movements with either arm. The double dissociation between imagery for hand and arm movements in the left cerebral hemispere is consistent with the hypothesis that grasping and reaching components of prehension involve dissociable planning mechanisms.

Recent neurophysiological research in the monkey has revealed bimodal neuronal cells with both tactile receptive fields on the hand and visual receptive fields that follow the hands as they move, suggesting the existence of a bimodal map of visuotactile space. Using a cross-modal congruency task, we examined the representtion ofvisuotactile space in normal people and in a split-brain patient (J. W.) as the right arm assumed different postures. The results showed that the congruency effects from distracting lights followed the hand around in space in normal people, but failed to do so in the split-brain patient when the hand crossed the midline. This suggests that cross-cortical connections are required to remap visual space to the current hand position when the hand crosses the midline.