Account of the Journey of Hieronimo di Santo Stefano, a Genovese (1495-1496) edited by R. H. Major, re-edited and introduced by Michael W. Charney

This translation of Hieronimo di Santo Stefano’s journey to Pegu in 1495-1496 was originally published in India in the Fifteenth Century Being a Collection of Narratives of Voyages to India, edited by R. H. Major, in 1857. The account was written in the form of a letter to Messer Giovan Jacobo Mainer. Only those portions related to Burma have been included in the version below

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined

Clinical Characteristics of Dialysis Related Sclerosing Encapsulating Peritonitis: Multi-center Experience in Korea

Sclerosing encapsulating peritonitis (SEP) is a rare but serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD), and is characterized by a progressive, intra-abdominal, inflammatory process resulting in the formation of sheets of new fibrous tissue, which cover, bind, and constrict the viscera, thereby compromising the motility of the bowel. No satisfactory estimate is available on the comparative incidence of dialysis related SEP and the pathogenesis of SEP still remains uncertain. Although recent therapeutic approaches have reported varying degrees of success, an efficient measure to detect, at an early stage, patients at risk for SEP would be beneficial and a standardized treatment regimen to prevent the illness is urgently needed. This study aimed to evaluate the clinical features of SEP and to identify the possible risk factors for the development of SEP in CAPD patients. We retrospectively reviewed by questionnaire SEP cases among CAPD patients from 7 university hospital dialysis centers in Korea, including Yonsei University, Ajou University, Catholic University, Inha University, Kyungpook University, Seoul National University and Soonchunhyang University, from January 1981 to December 2002. Out of a total of 4,290 CAPD patients in these centers, 34 cases developed SEP with an overall prevalence of 0.79%. The male to female ratio was 17:17. The median age of these patients was 44.5 years (range 19 - 66). The median duration of CAPD before SEP was 64 months (9 - 144) and 68% of patients (23/34) had been on CAPD for more than 4 years. Peritonitis (including two fungal cases) was the main cause of catheter removal in SEP (27 cases, 79%). Seventy-five percent of the cases (15/20) were administered β-blocker for a mean duration of 85 months (26 - 130). Among 10 cases with available peritoneal equilibration test (PET) data, 8 showed high transporter characteristics, and the remaining 2 were high average. Eighteen cases were diagnosed by clinical and radiologic methods, and 16 were surgically diagnosed. Eleven cases were surgically treated and the others were treated conservatively with intermittent total parenteral nutrition (TPN). The overall mortality rate was 24%. SEP is a serious, life threatening complication of CAPD. Most cases had a PD duration of more than 4 years, a history of severe peritonitis, and high transporter characteristics in PET. Therefore, to reduce the incidence of SEP, careful monitoring and treatment, including early catheter removal in patients with severe peritonitis, should be considered for long-term CAPD patients with the above characteristics

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met

Contains fulltext : 98431.pdf (publisher's version ) (Open Access)RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events

Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder - Possible Role for Methoxyindole Pathway

10.1371/journal.pone.0068283PLoS ONE87-POLN

Subjectification in Times of Indebtedness and Neoliberal/Austerity Urbanism

© 2016 The Author. Antipode © 2016 Antipode Foundation Ltd. How can we analyse the (re)emergence of squatting in relation to the current housing crisis in Italy? Centred on the case of Rome, the paper theorizes this return as resulting from processes of subjectification in the housing sector linked to the raising of indebtedness as a main dispositif of capitalism under neoliberal/austerity urbanism agendas. The political economy-oriented literature on neoliberal/austerity urbanism is bridged with the post-Marxist approach of Maurizio Lazzarato. Debt is seen as the archetype of social relations, shaping and controlling subjectivities, making the “work on yourself” essential to the reproduction of (indebted) society. However, given the circular nature of power, indebtedness can be generative of new processes of subjectification aimed at subverting the same power relation. In this sense, the paper operationalizes the conceptualization of Foucauldian subjectification recently proposed by Judith Revel, emphasizing how subjectification always results from (1) an action/gesture and (2) a consequent deconstruction of the identity

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types