Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field. Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

Erratum: Prediction for a Four-Neutron Resonance [Phys. Rev. Lett. 117, 182502 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.182502.

Prediction for a Four-Neutron Resonance.

We utilize various ab initio approaches to search for a low-lying resonance in the four-neutron (4n) system using the JISP16 realistic NN interaction. Our most accurate prediction is obtained using a J-matrix extension of the no-core shell model and suggests a 4n resonant state at an energy near E_{r}=0.8 MeV with a width of approximately Γ=1.4 MeV.

Clostridium difficile in Crete, Greece: epidemiology, microbiology and clinical disease.

We studied the epidemiology and microbiology of Clostridium difficile and the characteristics of patients with C. difficile infection (CDI) in Crete in three groups of hospitalized patients with diarrhoea: group 1 [positive culture and positive toxin by enzyme immunoassay (EIA)]; group 2 (positive culture, negative toxin); group 3 (negative culture, negative toxin). Patients in group 1 were designated as those with definitive CDI (20 patients for whom data was available) and matched with cases in group 2 (40 patients) and group 3 (40 patients). C. difficile grew from 6% (263/4379) of stool specimens; 14·4% of these had positive EIA, of which 3% were resistant to metronidazole. Three isolates had decreased vancomycin susceptibility. Patients in groups 1 and 2 received more antibiotics (P = 0·03) and had more infectious episodes (P = 0·03) than patients in group 3 prior to diarrhoea. Antibiotic administration for C. difficile did not differ between groups 1 and 2. Mortality was similar in all three groups (10%, 12·5% and 5%, P = 0·49). CDI frequency was low in the University Hospital of Crete and isolates were susceptible to metronidazole and vancomycin.

Esophageal perforation during laparoscopic adjustable gastric band: conversion to open sleeve gastrectomy and endoscopic stent placement.

Laparoscopic adjustable gastric band (LAGB) is one of the most popular bariatric surgical procedures both in Europe and United States, because it is considered to be a safe and effective way of treating morbid obesity. This minimally invasive frequently employed bariatric procedure has many reported complications, but only a few cases of esophageal perforation have been reported. We present a case of iatrogenic esophageal perforation in an 18-year-old patient occurring during attempt to place an adjustable gastric band laparoscopically, which was diagnosed intraoperatively. Conversion to open sleeve gastrectomy with primary suturing of the perforation and drainage were performed. On the early postoperative period leak from the intra-abdominal part of the esophagus was diagnosed and treated with endoscopic placement of a self-expandable metal stent. After 2-years of follow-up the patient continues to have no sequelae from the perforation or symptoms of dysphagia, while Excess Weight Loss is 74.

Psychological but not vasomotor symptoms are associated with temperament and character traits.

OBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.

Female sexuality after female cancer treatment: a clinical issue.

PURPOSE OF INVESTIGATION: The aim of the present study was to record how the treatment of female cancer may affect sexuality and interpersonal relations in the couple. MATERIAL AND METHODS: From September 2008 until February 2012, the authors prospectively studied 67 patients with breast cancer (Group A) and 43 with gynecological cancers (Group B). As control groups 33 patients with benign breast and 30 patients with benign gynecological lesions (group 0a and 0b respectively) were used. Sexuality and interpersonal relations were evaluated by a questionnaire. The authors also evaluated interpersonal relations focusing on sexual function at the time of diagnosis and a year after the initial treatment for cancer. RESULTS: A significant reduction of the "sexual desire", "sexual Arousal", and "orgasm" dimension was found in both cancer groups, in contrast to the control group, revealing no significant change. The "sexual enjoyment" scale was significantly decreased in gynecological cancer group but not in breast cancer group. While the score on the "relationship quality" dimension significantly increased in both cancer groups. In all groups, there was a significantly positive correlation between sexual function and enjoyment; on the contrary, there was a significantly negative correlation between relationship quality and sexual function and enjoyment. CONCLUSION: Sexual dysfunctions is a clinical problem which should be evidenced at the beginning of therapy, from the oncologists in order to provide integrated treatment to their patients.

Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).

Small bowel obstruction caused by inflammatory cytomegalovirus tumor in a renal transplant recipient: report of a rare case and review of the literature.

Cytomegalovirus (CMV) infection in renal transplant recipients can present as asymptomatic viremia or CMV syndrome or, in more severe cases, as tissue-invasive disease. CMV enteritis, a common manifestation of CMV invasive disease, usually presents with fever, abdominal pain, anorexia, nausea, and diarrhea, and can be rarely complicated by colon perforation, hemorrhage, or megacolon. CMV infection occurs primarily in the first 6 months post transplantation, when immunosuppression is more intense. We describe the case of a female renal transplant recipient with small bowel obstruction caused by CMV disease 7 years post renal transplantation. The patient presented with diarrhea and abdominal pain. Because of elevated CMV viral load, she was initially treated with antiviral therapy with transient response. Endoscopy and imaging tests showed obstruction of the terminal ileum and, subsequently, the patient underwent exploratory laparotomy when a right hemicolectomy was performed. Biopsy results confirmed the diagnosis of CMV enteritis. Epidemiologic characteristics, clinical presentation, diagnostic workup, therapeutic options, and morbidity-mortality rates of CMV infection/disease, in renal transplant recipients, are reviewed.

The impact of HPV diagnosis on women's sexual and mental health: preliminary findings.

PURPOSE OF INVESTIGATION: The objective of the present study was to demonstrate the impact of HPV diagnosis on sexual function and mental health of Greek women. METHODS: The study population included 51 patients who proceeded to the gynecological outpatient clinic of "Aretaieion" Hospital, Athens, during 2008-2009. The participants were asked to complete a questionnaire regarding demographic characteristics, knowledge on HPV, gynecological and sexual history, as well as questions regarding their mental and sexual health after the diagnosis. RESULTS: Mean age of the participants was 36 years and mean age of their first Pap smear test was 24.4 years. Mean age of HPV diagnosis was 34 years and mean number of sexual partners was four. Regarding mental health, the majority experienced anxiety after the HPV diagnosis as well as fear regarding their health in the future. Nearly half of the women experienced guilt and anger and some of them distress, shame, diminution of self-esteem and stigmatization. Diminution in the level of sexual interest and desire and decrease in sexual intercourse frequency were quite often reported. CONCLUSION: Except for the important physical impact of HPV infection, its diagnosis seems to trigger several negative feelings and reduce sexual desire.

Anatomically curated segmentation of human subcortical structures in high resolution magnetic resonance imaging: An open science approach.

Magnetic resonance imaging (MRI)-based brain segmentation has recently been revolutionized by deep learning methods. These methods use large numbers of annotated segmentations to train algorithms that have the potential to perform brain segmentations reliably and quickly. However, training data for these algorithms are frequently obtained from automated brain segmentation systems, which may contain inaccurate neuroanatomy. Thus, the neuroimaging community would benefit from an open source database of high quality, neuroanatomically curated and manually edited MRI brain images, as well as the publicly available tools and detailed procedures for generating these curated data. Manual segmentation approaches are regarded as the gold standard for brain segmentation and parcellation. These approaches underpin the construction of neuroanatomically accurate human brain atlases. In addition, neuroanatomically precise definitions of MRI-based regions of interest (ROIs) derived from manual brain segmentation are essential for accuracy in structural connectivity studies and in surgical planning for procedures such as deep brain stimulation. However, manual segmentation procedures are time and labor intensive, and not practical in studies utilizing very large datasets, large cohorts, or multimodal imaging. Automated segmentation methods were developed to overcome these issues, and provide high data throughput, increased reliability, and multimodal imaging capability. These methods utilize manually labeled brain atlases to automatically parcellate the brain into different ROIs, but do not have the anatomical accuracy of skilled manual segmentation approaches. In the present study, we developed a custom software module for manual editing of brain structures in the freely available 3D Slicer software platform that employs principles and tools based on pioneering work from the Center for Morphometric Analysis (CMA) at Massachusetts General Hospital. We used these novel 3D Slicer segmentation tools and techniques in conjunction with well-established neuroanatomical definitions of subcortical brain structures to manually segment 50 high resolution T1w MRI brains from the Human Connectome Project (HCP) Young Adult database. The structural definitions used herein are associated with specific neuroanatomical ontologies to systematically interrelate histological and MRI-based morphometric definitions. The resulting brain datasets are publicly available and will provide the basis for a larger database of anatomically curated brains as an open science resource.

Contrasting patterns of deficits in visuospatial memory and executive function in patients with major depression with and without ECT referral.

BACKGROUND: The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses. METHOD: Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups. CONCLUSIONS: A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.

Aggressive behaviour in schizophrenic patients after abrupt treatment discontinuation.

OBJECTIVE: This retrospective study examined the demographic, clinical and pharmacological factors associated with aggressive behaviour after abrupt discontinuation of medication in schizophrenic patients. METHOD: The study reports on a survey of 402 schizophrenic patients, who had abruptly discontinued their medication and had been involuntarily hospitalized to Psychiatric Hospital of Attika. The survey utilized the Discontinuation-Emergent Signs and Symptoms Checklist (DESS) to assess the signs and symptoms that patients exhibited (Rosenbaum et al., Biol Psychiatry 1998;44:77), as well the Aggression Scale (Delgado-Escueta et al., New England J Med 1981;305:711) to estimate the aggressive behaviour. Demographic and clinical variables as well as variables related to pharmacological treatment have been also investigated. RESULTS: Analyses revealed that the presence of aggressive behaviour after abrupt drug discontinuation was associated positively with previous history of aggression, male gender , abrupt discontinuation of anticholinergics, delusions, nervousness or anxiety, elevated mood, irritability and negatively with negative symptoms. These predictors can correctly classify 76.3% of patients with aggressive behaviour and 64.0% of patients without aggressive behaviour. CONCLUSION: These findings suggest that abrupt discontinuation of medication in schizophrenic patients may lead to aggressive behaviour, being connected at least in the acute phase with particular demographic, clinical and pharmacological parameters.

The oncologic conceptions of the great clinician, phtisiologist, pathologist and statistician Gaspard-Laurent Bayle (1774-1816).

Gaspard-Laurent Bayle was a 19th century eminent clinician, pathologist, phthisiologist and statistician that deserves our attention. His very advanced oncologic conceptions rank him among the all-time great pioneers of oncology.

The Nobel Prize laureate - father of anaphylaxis Charles-Robert Richet (1850-1935) and his anticancerous serum.

Professor of physiology Charles-Robert Richet, winner of the Nobel Prize in 1913, is best known for his work on anaphylaxis. However, with his collaborator Jules Héricourt studied the effects of antibody treatment and made the very first attempts to fight cancer with serotherapy. Being versatile, Richet contributed in neurology, psychology and was also a poet, playwrighter, pacifist and pioneer in aviation.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms.

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

A study of eating attitudes and related factors in a sample of first-year female Nutrition and Dietetics students of Harokopion University in Athens, Greece.

OBJECTIVE: To investigate eating attitudes and related factors in a sample of first-year female students of Harokopion University, Nutrition and Dietetics (ND) School. METHOD: The Eating Attitudes Test (EAT-26), a set of 12 male and female figures, and two questionnaires for demographic, clinical and nutritional data were administered to 53 ND students and 54 first-year female students of Athens Technological Institution Health Visitors (HV) School. RESULTS: The ND group scored higher in EAT-26 total score (p=0.05) and Diet subscale (p=0.02) than the HV group. EAT-26 score in the ND group correlated significantly with dinner avoidance (correlation coefficient: 0.3, p=0.02). Logistic regression analysis showed that avoidance of dinner (p=0.03), choosing leaner ideal women figures (p=0.005) and larger self images (p=0.01) were the three factors that could predict high EAT-26 scores in the ND group (EAT-26>or=20). CONCLUSIONS: First-year ND students might have more often disordered eating attitudes as opposed to students from other university programs.

Utilization of steel slag for Portland cement clinker production.

The aim of the present research work is to investigate the possibility of adding steel slag, a by-product of the conversion of iron to steel process, in the raw meal for the production of Portland cement clinker. Two samples of raw meals were prepared, one with ordinary raw materials, as a reference sample ((PC)(Ref)), and another with 10.5% steel slag ((PC)(S/S)). Both raw meals were sintered at 1450 degrees C. The results of chemical and mineralogical analyses as well as the microscopic examination showed that the use of the steel slag did not affect the mineralogical characteristics of the so produced Portland cement clinker. Furthermore, both clinkers were tested by determining the grindability, setting times, compressive strengths and soundness. The hydration products were examined by XRD analysis at 2, 7, 28 and 90 days. The results of the physico-mechanical tests showed that the addition of the steel slag did not negatively affect the quality of the produced cement.

[Electroconvulsive therapy: 80 years of use in psychiatry].

Electroconvulsive therapy (ECT) is the oldest among the early biological treatments introduced in psychiatry, and the only one still in use. In this paper we attempt a brief presentation of ECT usage over the last 80 years, since it was originally introduced. It is a safe, well-tolerated, and highly effective treatment option for major psychiatric disorders, such as mood disorders and schizophrenia, especially when there is an acute exacerbation of psychotic symptoms or if catatonic symptoms are prominent. ECT has also been used successfully for the treatment of Parkinson's disease, delirium, neuroleptic malignant syndrome, autism and agitation and depression in demented patients. There are no absolute contraindications. However, it is considered a high risk procedure for patients with increased intracranial pressure, recent myocardial infarction, recent cerebral hemorrhage or stroke, vascular aneurysm, retinal detachment and pheocromocytoma. Modern genetic and neuroimaging techniques have helped clarify possible mechanisms of action of ECT, but much remains unknown. Improvement of this method through a number of technical advancements has contributed in the reduction of side effects. Thus, modified ECT is currently considered as an effective and safe form of treatment even in vulnerable populations such as the geriatric patients, the adolescents and the pregnant patients. The mortality rate is very low, comparable to that of a minor anesthetic procedure. The most common adverse events are headache, nausea, myalgias and postictal delirium while the most severe are the cardiovascular side effects. Of note, the cognitive side effects especially amnesia, although transient, has been the focus of skepticism against the treatment. Major psychiatric disorders are chronic, recurring disorders. The relapse rate after a successful course of ECT without any intervention is extremely high. Pharmacotherapy or continuation ECT reduces equally the relapse rate up to 40%. Continuation and maintenance ECT, in combination with pharmacotherapy, have been successfully used in preventing relapse and recurrence. Gradual tapering off acute ECT treatments and individualized continuation and maintenance ECT treatments based on the needs of each patient seems the optimum clinical practice. Conclusively, despite impressive new developments in pharmacotherapy and in biological non pharmacological treatments ECT remains a valuable, irreplaceable treatment option for debilitating, resistant major psychiatric disorders.