Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.

Neural functional correlates of emotional processing in patients with first-episode psychoses: an activation likelihood estimation (ALE) meta-analysis.

BACKGROUND: Early emotional recognition impairment characterises rst-episode psychoses (FEP) and remains stable thereafter. Patients with FEP consistently show brain activation changes during emotional processing in functional neuroimaging studies. AIM AND METHODS: To identify and compare cerebral activation correlates of FEP patients and healthy controls (HCs) during emotional task performances, we performed an Activation Likelihood Estimation (ALE) meta-analysis of peer-reviewed functional magnetic resonance imaging (fMRI) studies. RESULTS: Five studies included 71 patients with FEP and 75 HCs. Within-group analyses showed that HCs activated during emotional task performance the bilateral inferior parietal lobule (BAs 39 and 40), left inferior frontal gyrus (BAs 9 and 47), right amygdala, left middle frontal gyrus (BA 9), right cingulate gyrus (BA 32), and right middle temporal gyrus (BA 21). FEP activations correlating with emotional tasks included the right cuneus (BA 17) and right angular gyrus (BA 39). CONCLUSIONS: During emotional task performance, FEP patients fail to activate an extensive brain network comprising emotional processing-related areas, including both cortical and subcortical areas.

Phase II study on lapatinib in advanced EGFR-positive chordoma.

BACKGROUND: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). RESULTS: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.

Functional neuroimaging in obsessive-compulsive disorder.

BACKGROUND AND AIM: Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling psychiatric disorder that usually emerges during childhood or adolescence. This paper aims to review the literature on functional neuroimaging in OCD, analysing the reported dysfunctional connectivity in the corticostriatothalamocortical circuitry. METHOD: This study included papers published in peer-reviewed journals dealing with functional imaging in OCD. RESULTS: Striatal dysfunction, mainly of the caudate nucleus, leads to inefficient thalamic gating, resulting in hyperactivity within the orbitofrontal cortex (intrusive thoughts) and the anterior cingulate cortex (non-specific anxiety). Compulsions consist of ritualistic behaviours performed to recruit the inefficient striatum and neutralise unwanted thoughts and anxiety. Functional neuroimaging findings are discussed against the background of specific cognitive impairments, mainly regarding visuospatial processing, executive functioning and motor speed. Cognitive deficits are partial and specific, matching imaging data. CONCLUSIONS: Several studies have targeted brain regions hypothesised to be involved in the pathogenesis of OCD, showing the existence of dysfunctional connectivity in the corticostriatothalamocortical circuitry. Improvements in spatial resolution of neuroimaging techniques may contribute to a better understanding of the neurocircuitry of OCD and other anxiety disorders.

Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption.

In a previously published double-blind, placebo-controlled study, we showed that probiotics intake exerted a positive effect on sleep quality and a general improvement across time in different aspects of the profile of mood state, like sadness, anger, and fatigue in 33 healthy individuals. The present work investigates the impact of the probiotic product, constituted of Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 (all former members of Lactobacillus genus), and Bifidobacterium longum 04, on the gut microbiota composition of the same cohort through a metabarcoding analysis. Both the placebo and probiotic treatments had a significant impact on the microbiota composition. Statistical analysis showed that the microbiota of the individuals could be clustered into three groups, or bacteriotypes, at the baseline, and, inherently, bacterial compositions were linked to different responses to probiotic and placebo intakes. Interestingly, L. rhamnosus and L. fermentum were retrieved in the probiotic-treated cohort, while a bifidogenic effect of maltodextrin, used as placebo, was observed. The present study shed light on the importance of defining bacteriotypes to assess the impact of interventions on the gut microbiota and allowed to reveal microbial components which could be related to positive effects (i.e. sleep quality improvement) to be verified in further studies.

[Predicting risk of suicide in bipolar and unipolar depression: correlation between temperament and personality]. / Prädiktion des Suizidrisikos bei bipolar und unipolar depressiven Patienten: Wechselwirkung von Temperament und Persönlichkeit.

OBJECTIVE: The aim of this study was to evaluate the roles of personality and affective temperament traits in the prediction of suicide risk in mood disorders. METHODS: The participants were 147 psychiatric inpatients with bipolar disorders I and II and major depressive disorder. Patients undertook the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness Scale. RESULTS: Sixty-four subjects were diagnosed with increased suicidal risk based on the Mini International Neuropsychiatric Interview (MINI). Logistic regression analysis resulted in two models predictive of MINI-based suicidal risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis further indicated that higher hyperthymic values are protective against hopelessness, while MINI-based suicidal intent is a predictor of hopelessness. CONCLUSIONS: Personality and affective temperament traits may have a role in the prediction of suicide.

Single-Scaffold Genome Sequence of Probiotic Strain Bifidobacterium breve BR03 (DSM 16604), Obtained by Combining Hybrid Sequencing and Optical Mapping.

Bifidobacterium breve BR03 (DSM 16604) is known for its health-promoting activity. We present a single-scaffold genome obtained by using a hybrid approach combining long- and short-read sequencing techniques integrated by an optical map. This approach could be set as an industry standard for probiotic strain characterization.

Immunocytochemical localization of calmodulin in intact and acrosome-reacted boar sperm.

Localization of calmodulin on intact and acrosome-reacted ionophore A23187 induced boar sperm has been performed with indirect immunofluorescence and immunoelectron microscopy. The results obtained with immunofluorescence are in agreement with previous reports. Immunoelectron microscopy was performed with the methods of preembedding immunostaining and on-grid post-embedding immunostaining of Lowicryl K4M sections with the protein A-colloidal gold. The presence of calmodulin is demonstrated in the acrosomal content and in the equatorial and postacrosomal regions of intact sperm. Apparently, calmodulin is released in association with the plasma membrane and the outer acrosomal membrane in acrosome-reacted sperm and it is maintained in the equatorial and postacrosomal regions. These results provide further evidence that also in mammalian sperm multiple classes of calmodulin-binding proteins may be present.

Identification of actin in boar spermatids and spermatozoa by immunoelectron microscopy.

Actin was localized in testicular spermatids and in ionophore-treated ejaculated sperm of boar by use of a monoclonal anti-actin antibody labeled with colloidal gold. With the on-grid postembedding immunostaining of Lowicryl K4M sections, actin was identified in the subacrosomal region of differentiating spermatids, in the microfilaments of the surrounding Sertoli cells, and in the myoid cells of the tubular wall. Ejaculated sperm, labeled with the preembedding method, showed actin between the plasma membrane and the outer acrosomal membrane of the equatorial segment. Indirect immunofluorescence was positive in the equatorial segment and in the acrosomal cap of intact sperm, whereas reacted sperm at the anterior head region retained fluorescence only in the inner acrosomal membrane. Rhodamine-phalloidin failed to stain intact and reacted sperm. The distribution of actin in sperm head membranes (inner acrosomal membrane, membranes of the equatorial segment), which are retained after the acrosome reaction, is discussed.

Immunocytochemical identification of actin in rabbit spermiogenesis and spermatozoa.

Actin was localized in testicular spermatids and in spermatozoa of rabbit by using a monoclonal anti-actin antibody and a specific antiserum against actin, labeled with colloidal gold. The antibody reactivity with sperm homogenates was determined by immunoblotting of one-dimensional gels. With on-grid postembedding immunostaining of Lowicryl K4M sections, actin was identified in the subacrosomal region of differentiating spermatids, and in four bulges situated between the inner acrosomal membrane and the nuclear envelope and in the anterior part of the postacrosomal region of ejaculated spermatozoa. Sperm actin was identified on two-dimensional gels as two spots in the isoelectric point and molecular weight corresponding to gamma and beta-isoforms of actin. Immunoblots stained with specific antibodies demonstrated that rabbit spermatozoa express gamma and beta-actin isoforms.

Immunosuppression after heart transplantation: prednisone and cyclosporine with and without azathioprine.

Fifty-four patients (group I) underwent isolated heart transplantation between July 1983 and January 1987 and were immunosuppressed with oral prednisone and cyclosporine. Twenty-three patients (group II) were transplanted between January 1987 and June 1988 and were immunosuppressed with oral prednisone, azathioprine, and cyclosporine, with lower targeted cyclosporine blood levels. The groups were similar in sex distribution of both donors and recipients. Primary cardiomyopathy was the primary recipient diagnosis in two thirds of patients in both groups. Donor age, graft ischemic time, and length of recipient hospitalization after transplant were similar. There was a trend toward transplantation of older patients in group II, and group II patients were more likely to receive hearts from local donors. Actuarial survival at 24 months was 75% in group I and 92% in group II. Patients who had triple-drug immunosuppression had statistically less early rejection but more early infections that tended to be minor. Hypertension requiring treatment occurred in 63% of group I patients and 62% of group II patients within the first 9 months after transplantation. Elevation of serum creatinine greater than 2.0 mg/dl occurred in 34% of group I patients and 15% of group II patients. A triple-drug immunosuppressive protocol is associated with less early rejection but more early minor infectious episodes. Although the incidence of hypertension is not reduced, there is a trend toward less nephrotoxicity and better survival.

Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase.

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of myocardial ischemic injury with oxygen-derived free radical scavengers.

Experimental data suggesting that oxygen-derived free radicals may play a role in the myocardial injury associated with ischemia and reperfusion are presented. In several studies of prolonged global myocardial ischemia, the administration of free radical scavenging agents, such as superoxide dismutase, catalase, and mannitol, resulted in significantly better recovery of left ventricular function following reperfusion. In a region-at-risk model of localized myocardial ischemia, both superoxide dismutase and allopurinol significantly reduced the extent of myocardial necrosis that developed following reversible coronary arterial branch occlusion. The manner in which oxygen-derived free radicals may be harmful is examined. In particular, the possibility that these toxic species are involved in the exacerbation of the ischemic injury that develops upon reflow and reoxygenation is examined.

Surgical treatment of postinfarction ventricular septal defect with aortic stenosis.

A 69-year-old man with an acute postinfarction ventricular septal defect was also found to have aortic stenosis. Successful management required closure of the postinfarction ventricular septal defect and replacement of the stenotic aortic valve. The contribution of aortic stenosis to the cause of the infarction and the postinfarction ventricular septal defect, as well as the implications for surgical management, are discussed.

Current indications, risks, and outcome after pericardiectomy.

A retrospective analysis of the records of 60 patients who underwent pericardiectomy over a 10-year period (1980 to 1990) at The Johns Hopkins Hospital was performed. Indications for operation were effusive disease in 24 patients and constriction in 36 patients. Six patients (10%) with pericardial effusion had pain as the primary symptom necessitating intervention. The operative approach for pericardiectomy was median sternotomy in 52 patients (4 patients required cardiopulmonary bypass) and left anterior thoracotomy in 8 patients. Nine patients (5 with constriction and 4 with effusion) with a prior limited pericardial procedure required formal pericardiectomy. The operative mortality rate for pericardial effusion and constriction was 4.2% and 5.6%, respectively. Follow-up (median follow-up, 56.9 +/- 38.2 months) was obtained on 56 patients (93.3%). Actuarial survival at 1 year, 5 years, and 10 years for all patients was 82.1% +/- 5.1%, 71.7% +/- 6.7%, and 59.8% +/- 12.2%, respectively. A Cox proportional hazards regression analysis was performed using 20 clinical variables. A history of malignancy, previous pericardial procedure, and preoperative New York Heart Association class IV were found to be predictors of poor survival. All patients who underwent operation primarily for effusion with associated pain are alive and have improved functional capacity without steroid use. We conclude that pericardiectomy can be performed with low mortality and can result in good long-term survival and improved functional capacity. Patients who are seen primarily with pain refractory to steroid therapy can be relieved of symptoms with operation.

Routine use of the left internal mammary artery graft in the elderly.

Left internal mammary artery (LIMA) grafts have better long-term patency rates than do saphenous vein grafts and result in improved late survival. The present study was undertaken to assess the results of LIMA grafting in the elderly. From 1980 through 1988, 723 patients 70 years of age or older had isolated coronary artery bypass grafting performed. During the first 5 years, only 11% of the elderly patients received LIMA grafts, whereas 86% having coronary artery bypass grafting since 1985 had LIMA grafts. Since 1986, LIMA use in the elderly has become routine, with 92% of patients receiving internal mammary artery grafts. During the first 5 years, elderly patients had a hospital mortality rate of 9.3%. Since 1985, the hospital mortality rate fell to 5.5%. In addition, the occurrence of major surgical complications was either unchanged or reduced in patients receiving LIMA grafts. Furthermore, late follow-up indicates a significantly improved 4-year survival rate in patients with internal mammary artery grafts compared with those without: 86 +/- 0.02% versus 77 +/- 0.03% (p less than 0.01). Analysis of multiple potential risk factors for early mortality was performed using multiple logistic regression and late survival using the Cox proportional hazards model. Although unmeasured predictor variables may confound retrospective analyses, LIMA grafting appears to be an independent predictor both of improved early and late survival.

Prolonged penile erection in the newborn.

An extensive review of the literature suggests that priapism or prolonged penile erection is extremely rare in the newborn. We present a term newborn whose clinical course of prolonged penile erection was a result of polycythemia. In the past, only 3 cases appear to have been associated with polycythemia. However, two of these cases had several other complicating factors. The remaining episodes have been described as idiopathic (7), or attributed to infection (1) or central nervous system insult (1). The recognition of this phenomenon and its historical record of clinical course is important in the newborn so inappropriate approaches to treatment may be avoided. Because of spontaneous detumescence in many instances, observation or nonsurgical management is advocated for the newborn with prolonged penile erection.

Initial experience using a catheterizable ileovesicostomy (Monti procedure) in children.

OBJECTIVES: To present a review of our experience using the recently described Monti ileovesicostomy as an alternative to appendicovesicostomy as a continent catheterizable stoma in children. METHODS: Between January and December 1997, a Monti ileovesicostomy was performed as part of a reconstructive procedure in 13 children. Mean patient age was 1 1 years, and diagnosis included neurogenic bladder in 11 patients, cloacal exstrophy in 1, and cloacal anomaly in 1 patient. Simultaneous bladder augmentation was performed in 10 children, bladder neck reconstruction or closure in 7, and Malone antegrade continent enema (MACE) in 4. RESULTS: All 13 patients have continent stomas (100%) and catheterize the Monti ileovesicostomy without difficulty. Mean follow-up was 7 months (range 1 to 14), and there have been no stomal problems or postoperative complications attributed to the ileal channel. CONCLUSIONS: The Monti ileovesicostomy is a new technique for creation of a continent catheterizable stoma and has allowed preservation of the appendix for the MACE procedure, providing an additional option in patients with an absent or inadequate appendix. Early results of this technique for pediatric reconstruction have been excellent.

Cloacal exstrophy.

Although each patient with cloacal exstrophy must be considered as a unique individual and much controversy still remains about the treatment of this complex syndrome, our review of the literature suggests that the previously detailed series of stages in the approach to this patient represents a conservative, individualized, yet successful approach.

Prenatal bladder outlet obstruction secondary to ureterocele.

We present 2 cases of prenatal hydroureteronephrosis and bladder outlet obstruction due to an obstructing ureterocele. Both neonates were stabilized and managed with early endoscopic decompression. Neither infant demonstrated significant function in the kidney ipsilateral to the ureterocele either before or after ureterocele puncture. There have been few cases reported of prenatal bladder outlet obstruction due to a ureterocele. Our limited experience has been poor with regard to salvaging the affected upper tract. Future definitive management will be tailored as more of these cases are documented.