DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia.

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (P<0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted DRD2 pathway co-expression in both mRNA data sets (all P<0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total N=368) and 29 patients with SCZ who performed the n-back task. Greater predicted DRD2 pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected P<0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total N=87; P<0.05). The findings on this DRD2 co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.

The first case of acinic cell carcinoma of the breast within a fibroadenoma: case report.

A case of acinic cell carcinoma of the breast is reported in a 26-year-old woman. She presented a lump in her right breast, that seemed to be a fibroadenoma. The open biopsy revealed a well-bordered fibroadenoma, together with a proliferation of cells characterized by serous acinar differentiation and eosinophilic cytoplasmic granules. Tumor cells stained for amylase, lysozyme, α-1-antichymotripsin, epithelial membrane antigen, S-100 protein, pan-cytokeratin, cytokeratin 7 and E-cadherin. Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 overexpression, CD10, P63, smooth muscle actin, cytokeratin 5/6 were negative. The sentinel node was negative. 8 months after surgery she is in good clinical conditions without recurrence or metastases.

Positive findings in preoperative testing prior to gastric banding: their real value.

AIM: Relations between laparoscopic adjustable gastric banding (LAGB), gastroesophageal reflux (GER) and hiatal hernia (HH) are controversial. In this context the role of preoperative investigations to assess upper gastrointestinal (GI) function and its impact on the approach to LAGB and outcomes remains unclear. The aim was to define the value of preoperative upper GI testing, and to relate the findings with postoperative outcomes. METHODS: Seventy-eight cases were enrolled among 250 patients undergoing LAGB from January 2010 to December 2011 in our Center for the Multidisciplinary treatment of severe obesity. Patients were submitted preoperatively to endoscopy and radiologic series with oral contrast to assess the state of upper GI mucosa, the presence of HH, GER or cardias incontinence. According to the findings, patients were assigned to group A, if one or both exams showed positive results; or to the control group B if both exams were negative. RESULTS: GI series showed GER in 14.1% of patients, HH in 6.4%, altered motility in 5.1%, gastritis in 3.1%and were negative in 75.6%. Endoscopy showed gastritis in 71.8%of patients, HH in 30.8%, esophagitis in 7.7%, duodenitis in 7.7%, LES incontinence in 8%; while only 21.8% of patients had a negative exam. Differences between group A and B are not statistically significant in terms of pre- and post-operative BMI, EBWL%, long-term complications, time and number of regulations. CONCLUSION: Positive findings in preoperative testing rarely postpone or change the surgical approach and postoperative outcomes. Our results encourage the omission of upper GI series from routine evaluation protocol prior to LAGB.

Gastric emptying after sleeve gastrectomy: statistical evidence of a controlled prospective study with gastric scintigraphy.

AIM: Laparoscopic sleeve gastrectomy (LSG) is a stand-alone bariatric procedure, its feasibility and efficacy being confirmed by long-term data. The effect of the procedure is believed to be based on the gastric restriction and reduction of ghrelin. Nevertheless it remains still controversial the role of LSG on gastric emptying and the impact that this may have on weight loss outcomes. Our aim is to assess gastric emptying after LSG using gastric scintigraphy. METHODS: For this prospective randomized study, 45 patients undergoing LSG at our Centre for the Multidisciplinary Treatment of Severe Obesity from April 2009 to April 2011 were enrolled and observed prospectively (Group A). The inclusion criteria followed the guidelines for bariatric surgery. All patients performed gastric emptying scintigraphy through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99. Group A performed the exam before (A1) and after the operation (A2). A control group (Group B) included 20 patients undergoing scintigraphic assessment for other reasons. RESULTS: LSG was performed following a standardized technique. No complications were observed. The scintigraphic study showed a reduced half-life tracer (A1 vs. A2: 80.4±16.5 min vs. 64.3±22 min P=0.06), without a significant difference. Comparing the two groups no differences occurred before operation (B vs. A1). Gastric emptying time resulted significatively reduced in group A2 rather than in group A1 and B. CONCLUSION: Gastric motility plays a role in the pathogenesis of obesity. Our experience suggests that LSG reduces gastric emptying time, but further studies are necessary to reach statystical significativity.

Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage.

Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 µM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH.

Use of Tachosil® in bariatric surgery: preliminary experience in control of bleeding after sleeve gastrectomy.

AIM: Laparoscopic sleeve gastrectomy (LSG) is one of the most common procedures of bariatric surgery. Nevertheless complications after LSG are common, the most frequent is bleeding. Our purpose was to reduce bleeding after gastric resection, thus reducing the risk of anemia. METHODS: The study took part in our Multidisciplinary Obesity Treatment Centre, between May 2008 and January 2010. Thirty patients were candidates to SG. They were enrolled in this prospective, parallel group, single-blind randomized trial, to proof the effectiveness and safety of the use of hemostatic-sealant drug Tachosil® as a reinforcement of the suture line in sleeve gastrectomy. Patients were enrolled in Group A when TachoSil® was used and Group B if not. We collected data about weight loss every month, RBC, Hb, PLT, ESR, CRP, WBC in the first week daily and at 2, 4 and 6 months on follow-up. RESULTS: Two groups did not significantly differ for mean age, mean of body weight (118.5 vs. 121.9 kg), BMI (48.4 vs. 49.6 kg/m2), operation time (108 vs. 102 min), hospitalization duration (6.5 vs. 7 days). In group B mean drainage fluid collection was 120, 80 and 60 mL on 1st, 2nd and 3rd postoperative day. Tube removal occurred on average on 5th postoperaive day. In group A (no drainage) control echogram ruled out any fluid collection. RBC, Hb and PLT decreased from 2nd postoperative day. Decrease of PLT was non-significantly different. Decrease of RBC and Hb was significantly different (-0.4 x 106/mL vs. -1.7 x 106/mL; -0.5 g/dL vs. -1.2 g/dL). All other values were not different between groups. CONCLUSION: In this prospective experience the hemostatic-sealant drug Tachosil®, that contains a collagen sponge coated by human fibrinogen and thrombin was shown to reduce post-operatory bleeding and probably promote optimal wound healing.

Heliosphere Bag in the treatment of severe obesity: preliminary experience.

BACKGROUND: Various intragastric balloons have been used in obese patients for temporary weight loss. Recently, a new balloon, the Heliosphere Bag, was proposed. In a preliminary study, we evaluated the safety and efficacy of this device. METHODS: The Heliosphere Bag was used in 10 patients, selected according to the guidelines for obesity surgery. The manufacturer's instructions were followed in positioning the device. Heliosphere Bag positioning was performed, after diagnostic endoscopy, under unconscious sedation. After placement, the balloon was slowly inflated with 840-960 cc of air, which gives the inflated final volume of 650-700 cc of air, as the air is compressed. On the first and second post-treatment day, intravenous saline (30-35 ml/kg/d) with omeprazole (20 mg/d), ondansetron (8 mg/d) and butylscopolamine bromide (20 mg t.i.d.) were given to all patients. All patients from day 3 after placement began liquid diet and were discharged home on day 4 on a 1000 kcal diet (carbohydrate 146 g, lipid 68 g, protein 1 g/kg ideal weight). After 6 months, the Heliosphere Bag was removed. The patients were followed monthly, and complications and their treatment, post-placement symptoms, BMI and %EWL were recorded. Data were expressed as mean +/- SD. RESULTS: From Sept-Dec 2004, 10 patients (5M/5F) underwent Heliosphere Bag placement, with age 35.2 +/- 15.7 years (17-49), BMI 43.3 +/- 8.1 kg/m(2) (35-51.2), and weight 126.8 +/- 23.7 kg (98.4-148). Heliosphere Bag positioning was quite difficult in all patients due to low pliancy and large size of the bag, causing patient discomfort. System failure at time of Heliosphere Bag positioning was observed in 5/10 patients (50%). At time of removal, the Heliosphere Bag was not found in the stomach in one patient. In 3 other patients, the balloon was found partially deflated. At the time of balloon removal after 6 months, BMI was 37.4 +/- 13.4 (28.9-42.1) and %EWL was 29.1 +/- 20.1 (9.0-57.4). BMI loss was 5.2 +/- 13.1 (1.9-11.2) and mean weight loss was 17.5 +/- 16.2 kg (5-33). CONCLUSIONS: Although weight loss was satisfactory, this device cannot be considered an advance for the temporary treatment of morbid obesity. This balloon still has some instrumental and technical problems that need to be solved: high rate of system failure at positioning, high rate of spontaneous deflation, absence of a marker such as methylene blue, and large size with low pliability that cause significant patient discomfort.