Short-Term Bilateral Adrenalectomy: Biochemical and Morphological Alterations in the Rat Hippocampus

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative stress markers; reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) over the course of time (0.5, 2, 4, 12 hours, 1, 3, 7, 14 days) in hippocampus of male Wistar rats. Results showed significant elevation of pro-inflammatory cytokines IL-1β at 4 hours, 1, 3, 7 days, whereas, IL-6 was significantly increased at 2 and 4 hours, 1 and 3 days in ADX compared to sham rats. After 7 days, elevation of both cytokines returned to control levels. However, TNF-α levels were significantly elevated at 2, 4 and 12 hours and 14 days in adrenalectomized compared to sham rats. A significant decrease of insulin-like growth factor-1 (IGF-1) levels was observed at 12 hours after ADX and remained consistent at 1, 3, 7, and 14 days compared to sham rats. However, β-nerve growth factor (β-NGF) was significantly reduced in ADX compared to sham rats only at 14 days. A time dependent increase in degenerated neurons in the dorsal blade of the dentate gyrus (DG) was observed from 3 to 14 days after ADX. An early up-regulation of microglia was observed on day three, whereas, increase in astroglia in the hippocampus was observed at 7 days ADX. After 14 days of ADX we observed a progression of microglia and astroglia up-regulation all over the DG of adrenalectomized rats’ hippocampi compared to sham rats. The antioxidant CAT increased at 3, 7 and 14 days in an effort to protect the neurons. However, oxidative stress was manifested in the ADX compared to the sham rats due to significant decrease of GSH after 7 and 14 days, with a simultaneous increase of MDA, after 7 and 14 days of ADX. Taking these findings together, we suggest that the early inflammatory components and loss of growth factors might contribute to the initiation of the biological cascade responsible for subsequent hippocampal neuronal cell death in the current neurodegenerative animal model

The relationship of bullying and workplace stress moderated by job scope

Previous studies showed that bullying factors, workloads, office politics and favoritism affect the workplace stress in the organization. An organization must address this problem with a systematic employee valuation and strategic leadership. The system also involves job description whereby it requires a more specific, clear and precise specification in order to tackle with the amount of workloads that exceed the job description. Thus this study aims to examine the relationship between bullying and workplace stress moderate by job scope. This study was conducted on employees from the top 5 cooperative registered under Federal Territory of Kuala Lumpur. The relationship between bullying (threat, contempt and sabotage) and workplace stress was examined using Pearson correlation analysis method to determine the existence of a relationship between the variables. The results showed that threat is significantly related to workplace stress (r = -.274, p < 0.01), contempt is significantly related to workplace stress (r = .317, p < 0.01) and sabotage is significantly related to workplace stress (r = -.350, p < 0.01). The hierarchical regression analysis was used to determine the mediator effect on the relationship between bullying and workplace stress. The finding showed that there was a moderation effect of job scope on the relationship between workplace bullying and workplace stress

Exploring Regions of Interest: Visualizing Histological Image Classification for Breast Cancer using Deep Learning

Computer aided detection and diagnosis systems based on deep learning have shown promising performance in breast cancer detection. However, there are cases where the obtained results lack justification. In this study, our objective is to highlight the regions of interest used by a convolutional neural network (CNN) for classifying histological images as benign or malignant. We compare these regions with the regions identified by pathologists. To achieve this, we employed the VGG19 architecture and tested three visualization methods: Gradient, LRP Z, and LRP Epsilon. Additionally, we experimented with three pixel selection methods: Bins, K-means, and MeanShift. Based on the results obtained, the Gradient visualization method and the MeanShift selection method yielded satisfactory outcomes for visualizing the images

Monoclonal Gammopathy of Undetermined Significance with Amyloid Deposition in the Lung and Non-Amyloid Eosinophilic Deposition in the Brain: A Case Report

Background. Monoclonal gammopathy of undetermined significance (MGUS) is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER) after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH) included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic), incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP) as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT) revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), rheumatoid factor (RF), cryoglobulin, and antiglomerular basement membrane (anti-GBM) antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always necessary. Further research is needed in order to better define the optimal treatment and management strategies of MGUS and its complications

Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation.

The recently described species Candida dubliniensis has been recovered primarily from superficial oral candidiasis in HIV-infected patients. No clinically documented invasive infections were reported until now in this patient group or in other immunocompromised patients. We report three cases of candidemia due to this newly emerging Candida species in HIV-negative patients with chemotherapy-induced immunosuppression and bone marrow transplantation

Stereological Evidence of Non-Selective Hippocampal Neurodegeneration, IGF-1 Depletion, and Behavioral Deficit following Short Term Bilateral Adrenalectomy in Wistar Rats

The development of animal models to study cell death in the brain is a delicate task. One of the models, that was discovered in the late eighties, is the induction of neurodegeneration through glucocorticoid withdrawal by adrenalectomy in albino rats. Such a model is one of the few noninvasive models for studying neurodegeneration. In the present study, using stereological technique and ultrastructural examination, we aimed to investigate the impact of short-term adrenalectomy (2 weeks) on different hippocampal neuronal populations in Wistar rats. In addition, the underlying mechanism(s) of degeneration in these neurons were investigated by measuring the levels of insulin-like growth factor-1 (IGF-1) and β-nerve growth factor (β-NGF). Moreover, we examined whether the biochemical and histological changes in the hippocampus, after short-term adrenalectomy, have an impact on the cognitive behavior of Wistar rats. Stereological counting in the hippocampus revealed significant neuronal deaths in the dentate gyrus and CA4/CA3, but not in the CA2 and CA1 areas, 7 and 14 days post adrenalectomy. The ultrastructural examinations revealed degenerated and degenerating neurons in the dentate, as well as CA4, and CA3 areas, over the course of 3, 7 and 14 days. The levels of IGF-1 were significantly decreased in the hippocampus of ADX rats 24 h post adrenalectomy, and lasted over the course of two weeks. However, β-NGF was not affected in rats. Using a passive avoidance task, we found a cognitive deficit in the ADX compared to the SHAM operated rats over time (3, 7, and 14 days). In conclusion, both granule and pyramidal cells were degenerated in the hippocampus following short-term adrenalectomy. The early depletion of IGF-1 might play a role in hippocampal neuronal degeneration. Consequently, the loss of the hippocampal neurons after adrenalectomy leads to cognitive deficits

Emergence and pandemic spread of small ruminant lentiviruses

Small ruminant lentiviruses (SRLVs) cause chronic, persistent infections in populations of domestic sheep (Ovis aries) and goats (Capra hircus) worldwide. The vast majority of SRLV infections involve two genotypes (A and B) that spread in association with the emergence of global livestock trade. However, SRLVs have likely been present in Eurasian ruminant populations since at least the early Neolithic period. Here, we use phylogenetic and phylogeographic approaches to reconstruct the origin of pandemic SRLV strains and infer their historical pattern of global spread. We constructed an open computational resource (‘Lentivirus-GLUE’) via which an up-to-date database of published SRLV sequences, multiple sequence alignments (MSAs), and sequence-associated metadata can be maintained. We used data collated in Lentivirus-GLUE to perform a comprehensive phylogenetic investigation of global SRLV diversity. Phylogenies reconstructed from genome-length alignments reveal that the deep divisions in the SRLV phylogeny are consistent with an ancient split into Eastern (A-like) and Western (B-like) lineages as agricultural systems disseminated out of domestication centres during the Neolithic period. These findings are also consistent with historical and phylogeographic evidence linking the early 20th century emergence of SRLV-A to the international export of Central Asian Karakul sheep. Investigating the global diversity of SRLVs can help reveal how anthropogenic factors have impacted the ecology and evolution of livestock diseases. The open resources generated in our study can expedite these studies and can also serve more broadly to facilitate the use of genomic data in SRLV diagnostics and research

WiseEye: next generation expandable and programmable camera trap platform for wildlife research

Funding: The work was supported by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. The work of S. Newey and RJI was part funded by the Scottish Government's Rural and Environment Science and Analytical Services (RESAS). Details published as an Open Source Toolkit, PLOS Journals at: http://dx.doi.org/10.1371/journal.pone.0169758Peer reviewedPublisher PD

Niche-specific regulation of central metabolic pathways in a fungal pathogen

To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis