Characterization of the Myocardial Inflammatory Response in Acute Stress-Induced (Takotsubo) Cardiomyopathy

This work was supported by grants from NHS Grampian Endowments and British Heart Foundation Project Grant no. PG/15/108/31928 The authors have reported that they have no relationships relevant to the contents of this paper to disclose.Peer reviewedPublisher PD

Secondary infertility caused by the retention of fetal bones after an abortion: a case report

<p>Abstract</p> <p>Introduction</p> <p>Unwanted contraception through prolonged retention of fetal bone is a rare cause of secondary infertility. It is usually associated with a history of abortion, either spontaneous or induced.</p> <p>Case presentation</p> <p>We describe a case of intrauterine retention of fetal bone diagnosed 8 years after the termination of a pregnancy. The patient had no complaints of pain, irregular vaginal bleeding or discharge. A hysteroscopy was performed and irregular structures were removed. These fragments were fetal bones, which probably functioned as an intrauterine contraceptive device. After removal of the fetal bone fragments the patient conceived spontaneously within 6 months.</p> <p>Conclusion</p> <p>This case report stresses the importance of taking a thorough history and evaluation of the endometrium by transvaginal ultrasound or hysteroscopy in women with secondary infertility.</p

Animals can assign novel odours to a known category

The ability to identify a novel stimulus as a member of a known category allows an organism torespond appropriately towards it. Categorisation is thus a fundamental component of cognition andan essential tool for processing and responding to unknown stimuli. Therefore, one might expectto observe it throughout the animal kingdom and across sensory domains. There is much evidenceof visual categorisation in non-human animals, but we currently know little about this process inother modalities. In this experiment, we investigated categorisation in the olfactory domain. Dogswere trained to discriminate between 40 odours; the presence or absence of accelerants formed thecategorical rule. Those in the experimental group were rewarded for responding to substrates withaccelerants (either burnt or un-burnt) and inhibit responses to the same substrates (either burnt or unburnt)without accelerants (S+ counterbalanced). The pseudocategory control group was trained onthe same stimuli without the categorical rule. The experimental group learned the discrimination andanimals were able to generalise to novel stimuli from the same category. None of the control animalswere able to learn the discrimination within the maximum number of trials. This study provides the firstevidence that non-human animals can learn to categorise non-biologically relevant odour information

Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease

BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb-/- mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb-/- colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb-/- rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb-/- aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb-/- HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies

Psychopathology and affect dysregulation across the continuum of psychosis: A multiple comparison group study

This is the peer reviewed version of the following article: Taylor, H. E., Stewart, S. L. K., Dunn, G., Parker, S., Bentall, R. P., Birchwood, M., & Morrison, A. P. (2014). Psychopathology and affect dysregulation across the continuum of psychosis: A multiple group comparison study. Early Intervention in Psychiatry, 8(3), 221-228. DOI: 10.1111/eip.12064, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/eip.12064/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingAim: There is evidence that psychotic-like phenomena can be detected within the general population and that psychotic experiences lie on a continuum which also spans affective states. We aimed to investigate comparisons of a first episode psychosis group, an ‘at-risk mental state group’ and a help-seeking control group with non-patients to explore whether affective states lie on a continuum of psychosis. Method: Measures of psychotic-like experiences, social anxiety and depression were administered to 20 patients experiencing first episode psychosis (FEP), 113 patients experiencing an ‘at-risk’ mental state (ARMS), 28 patients who were help-seeking but not experiencing a FEP or ARMS (HSC) and 30 non-clinical participants (NC). Results: For distress in relation to psychotic-like experiences, the FEP, ARMS and HSC groups scored significantly higher than the NC group for the perceptual abnormalities and non-bizarre ideas. In terms of severity of psychotic experiences, the FEP scored the highest, followed by the ARMS group, followed by the HSC and NC group. The clinical groups scored significantly higher for depression than the non-clinical group. Interestingly, only the FEP and the ARMS group scored significantly higher than non-patients for social anxiety. Conclusions: These findings suggest that a psychosis continuum exists, however this does not suggest that both psychosis and affective symptoms lie on the same continuum, rather it would appear that the presence of such affective states that may affect help-seeking behavior and clinical status. The implications of these findings for clinical practice are discussed

Scale-up and optimization of the synthesis of dual CBP/BRD4 inhibitor ISOX-DUAL

ISOX-DUAL is a dual inhibitor of CBP/p300 (IC50 = 0.65 μM) and BRD4 (IC50 = 1.5 μM) bromodomains, and a useful chemical probe for epigenetic research. Aspects of the published synthetic route to this compound and its analogues are small-scale, poor-yielding or simply unamenable to scale-up without optimization. Herein we describe the development of a refined synthesis that circumvents the challenges of the original report, with notable improvements to several of the key synthetic transformations. Moreover, a general Suzuki Miyaura protocol for the late stage installation of alternative dimethyl-isoxazole acetyl-lysine (KAc) binding motifs is presented

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village

Elevated CRP and TNF-α Levels are Associated with Blunted Neural Oscillations Serving Fluid Intelligence

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual\u27s plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders