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Introduction22q11.2 Deletion Syndrome (22q11.2DS) represents a congenital syndrome with several clinical features. It entails a 25% risk of psychotic onset in lifespan. 22q11.2DS is a reliable model for biological vulnerability to schizophrenia.ObjectivesWith the hypothesis of similar impairments in schizophrenia and 22q11DS, to investigate a possible correlation between Social Cognition (SC) and Interpersonal Functioning (FU).MethodsSample consists of 1735 adults: 893 schizophrenic subjects (SCZ); 18 with 22q11.2DS and psychosis (DEL_SCZ); 44 22q11.2DS individuals (DEL); 780 healthy controls (HC). SCZ and HC data come from a multicentric study by Network for Research on Psychoses. SC was assessed with The Awareness of Social Interference Test (TASIT, consisting of three sections: T1= Emotion Recognition; T2=Minimal Social Inference; T3=Social Inference Enriched). The Specific Levels of Functioning (SLOF) interview was employed.ResultsDEL_SCZ (p<0.001) and SCZ (p<0.001) showed impairments in each TASIT sections compared to HC. Significant deficits in interpersonal functioning area were found in SCZ (p<0.001) compared to HC. The interpersonal functioning domain showed a positive correlation with SC in HC (T1: r=0.097; p<0.001; T2: r=0.120; p=0.001; T3: r=0.121; p=0.001); DEL (T1: r=0.380; p=0.024; T2: r=0.466; p=0.005) and SCZ (T1: r=0.113, p=0.001; T2: r=0.110, p=0.001; T3: r=0.134; p<0.001).ConclusionsSC deficits both in subjects with 22q11.2DS and in people with schizophrenia suggest a role of endophenotypes. SC is directly correlated to interpersonal functioning in 22q11.2DS without psychosis and people with schizophrenia. DEL_SCZ may suffer from deeper cognitive and symptomatic conditions that both impact differently on FU.

Background: Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. Aims: We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). Patients and methods: Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. Results: Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. Conclusion: Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.

Background: The aim of the PROMETEO-01 Study was to define the diagnostic accuracy of imaging techniques in colorectal cancer liver metastasis (CRCLM) patients. Methods: Patients referred to Bologna S. Orsola-Malpighi Hospital performed a computed-tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET/CTscan (PET/CT) and liver contrast-enhanced-ultrasound (CEUS); CEUS was also performed intraoperatively (i-CEUS). Every pathological lesion was compared with imaging data. Results: From December 2007 to August 2010, 84 patients were enrolled. A total of 51 (60.71%) resected patients were eligible for analysis. In the lesion-by-lesion analysis 175 resected lesions were evaluated: 67(38.3%) belonged to upfront resected patients (group-A) and 108 (61.7%) to chemotherapy-pretreated patients (group-B). In all patients the sensitivity of MR proved better than CT (91% vs 82%; P =0.002), CEUS (91 vs 81%; P =0.008) and PET/CT (91% vs 60%; P =0.000), whereas PET/CT showed the lowest sensitivity. In group-A the sensitivity of i-CEUS, MR, CT, CEUS and PET/CT was 98%, 94%, 91%, 84% and 78%, respectively. In group-B the i-CEUS proved equivalent in sensitivity to MR (95% and 90%, respectively, P =0.227) and both were significantly more sensitive than other procedures. The CT sensitivity in group-B was lower than in group-A (77% vs 91%, P =0.024). Conclusions: A thoraco-abdominal CT provides an adequate baseline evaluation and guides judgment as to the resectability of CRCLM patients. In the subset of candidates for induction chemotherapy to increase the chance of liver resection, the most rational approach is to add MR for the staging and restaging of CRCLM.

Background: The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma. Methods: Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m −2 i.v. followed by weekly doses of 250 mg m −2 , cisplatin 75 mg m −2 i.v. on day 1, docetaxel 75 mg m −2 i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease. Results: Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5–52.9). Median time to progression was 5 months (95% CI, 3.7–5.4). Median survival time was 9 months (95% CI, 7–11). The most frequent grades 3–4 toxicity was neutropenia (44.4%). No toxic death was observed. Conclusions: The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab.

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor‐ß (TGFß), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46‐fold increase in CTGF mRNA expression (p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFß‐induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation (p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) (p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFß, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.

Inflammatory bowel disease consists of Crohn’s disease (CD) and ulcerative colitis (UC). A major clinical problem in some patients is to differentiate clearly between these entities, which is important when planning appropriate medical and surgical treatment. Connective tissue growth factor (CTGF), a novel peptide involved in fibrotic disorders, was analyzed in the present study in CD and UC patients to evaluate its possible role in these two disorders. Twenty-five normal human intestinal tissue samples were obtained through an organ donor program. CD tissues were obtained from 28 individuals undergoing partial intestinal resection (17 small bowel; 11 large bowel) due to complications of the disease. UC tissue samples were obtained from 16 patients undergoing colectomy due to complications of the disease. Expression of CTGF was studied by Northern blot analysis. In situ hybridization was used to localize mRNA moieties in the tissue samples. Northern blot analysis revealed an average 5-fold increase in CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were comparable to those of normal controls. However, UC tissue samples exhibited enhanced TGF-β1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD samples showed CTGF mRNA localized especially in fibroblasts within the submucosal layer, around lymph follicles and in some areas of intense damage in the proximity of the luminal surface, whereas inflammatory cells were devoid of any CTGF mRNA signal. The present data indicate that CTGF plays a different role in IBD and might be useful, especially in those cases with unusual disease presentation, to better differentiate UC and CD. In addition, our data indicate a crucial role for CTGF in CD, where fibrosis and stenosis are frequent complications that require surgery.

The pathophysiology of pain in pancreatic diseases is complex and multifactorial. Human data are available only for chronic pancreatitis patients and sometimes for pancreatic cancer. For acute pancreatitis, only animal data are available to date. The various hypotheses attempting to explain the genesis of pain also reflect the different therapeutical approaches to pain in these patients. The “neurogenic inflammation” hypothesis is a theory supported by various studies of all pancreatic disorders. Immunohistological reports have shown that the amount of neurotransmitters, such as substance P and its receptor calcitonin gene–related peptide and other neurotransmitters, is increased in afferent pancreatic nerves, and a correlation between pain and immune cell infiltration of the nerves has been described mainly in chronic pancreatitis patients. The most interesting finding is the existence of a spatial relationship between peptidergic neurons and inflammatory cells. Furthermore, there is the intriguing possibility of functional interaction among neuropeptides, immune cells, cytokines, and nerve growth factors.

The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%-2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome.