Effect of induced hyperthyroidism on pancreas of adult female albino rats

Introduction: A condition known as hyperthyroidism can lead to a wide range of health issues, including osteoporosis, oxidative liver damage, diabetes mellitus, as well as cardiovascular disease.Objective: To examine the detrimental effects of hyperthyroidism on the pancreatic structure of adult female albino rats.Materials and Methods: twenty-one adult virgin female albino rats were assigned to 2 groups; control and induction of hyperthyroidism. Serological analysis to assess thyroid functions, oxidative stress and lipid peroxidation analysis was carried out. Pancreatic samples were processed for light microscopic examination.Results: Hyperthyroidism caused both biochemical and histological changes on pancreas of adult female albino rats. The biochemical changes in the form of significant decreased in the thyroid stimulating hormone serum level, significant reduction in level of serum superoxide dismutase and the malondialdehyde level was significantly increased in the hyperthyroid rats. The histological changes were loss of its general architecture. The pancreatic acini appeared irregular, vacuolated and had dark nuclei. Some islets of Langerhans appeared shrunken and the acini did not have the normal smooth demarcation from the surface.Conclusion: Hyperthyroidism seriously affected the histological structure of the pancreas with subsequent disturbance in the biochemical markers

Modeling the role of fomites in a norovirus outbreak

Norovirus accounts for a large portion of the gastroenteritis disease burden, and outbreaks have occurred in a wide variety of environments. Understanding the role of fomites in norovirus transmission will inform behavioral interventions, such as hand washing and surface disinfection. The purpose of this study was to estimate the contribution of fomite-mediated exposures to infection and illness risks in outbreaks. A simulation model in discrete time that accounted for hand-to-porous surfaces, hand-to-nonporous surfaces, hand-to-mouth, -eyes, -nose, and hand washing events was used to predict 17 hr of simulated human behavior. Norovirus concentrations originated from monitoring contamination levels on surfaces during an outbreak on houseboats. To predict infection risk, two dose-response models (fractional Poisson and 2F1 hypergeometric) were used to capture a range of infection risks. A triangular distribution describing the conditional probability of illness given an infection was multiplied by modeled infection risks to estimate illness risks. Infection risks ranged from 70.22% to 72.20% and illness risks ranged from 21.29% to 70.36%. A sensitivity analysis revealed that the number of hand-to-mouth contacts and the number of hand washing events had strong relationships with model-predicted doses. Predicted illness risks overlapped with leisure setting and environmental attack rates reported in the literature. In the outbreak associated with the viral concentrations used in this study, attack rates ranged from 50% to 86%. This model suggests that fomites may have accounted for 25% to 82% of illnesses in this outbreak. Fomite-mediated exposures may contribute to a large portion of total attack rates in outbreaks involving multiple transmission modes. The findings of this study reinforce the importance of frequent fomite cleaning and hand washing, especially when ill persons are present.12 month embargo; published online: 04 Feb 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Xeno-free trans-differentiation of adipose tissue-derived mesenchymal stem cells into glial and neuronal cells.

Mesenchymal stem cells (MSCs) are undifferentiated cells that have the ability of self-renewal and trans-differentiation into other cell types. They hold out hope for finding a cure for many diseases. Nevertheless, there are still some obstacles that limit their clinical transplantation. One of these obstacles are the xenogeneic substances added in either proliferation or differentiation media with subsequent immunogenic and infectious transmission problems. In this study, we aimed to replace fetal bovine serum (FBS), the main nutrient source for MSC proliferation with xeno-free blood derivatives. We tested the effect of human activated pure platelet-rich plasma (P-PRP) and advanced platelet-rich fibrin (A-PRF) on the proliferation of human adipose derived-MSCs (AD-MSCs) at different concentrations. For the induction of MSC neural differentiation, we used human cerebrospinal fluid (CSF) at different concentrations in combination with P-PRP to effect xeno-free/species-specific neuronal/glial differentiation and we found that media with 10% CSF and 10% PRP promoted glial differentiation, while media with only 10% PRP induced a neuron-like phenotype

Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species

Arthroscopic medial meniscus trimming or repair under nerve blocks: Which nerves should be blocked?

Background: This study aimed to determine the role of the sciatic and obturator nerve blocks (in addition to femoral block) in providing painless arthroscopic medial meniscus trimming/repair. Materials and Methods: One hundred and twenty patients with medial meniscus tear, who had been scheduled to knee arthroscopy, were planned to be included in this controlled prospective double-blind study. The patients were randomly allocated into three equal groups; FSO, FS, and FO. The femoral, sciatic, and obturator nerves were blocked in FSO groups. The femoral and sciatic nerves were blocked in FS group, while the femoral and obturator nerves were blocked in FO group. Intraoperative pain and its causative surgical maneuver were recorded. Results: All the patients (n = 7, 100%) in FO group had intraoperative pain. The research was terminated in this group but completed in FS and FSO groups (40 patients each). During valgus positioning of the knee for surgical management of the medial meniscus tear, the patients in FS group experienced pain more frequently than those in FSO group (P = 0.005). Conclusion: Adding a sciatic nerve block to the femoral nerve block is important for painless knee arthroscopy. Further adding of an obturator nerve block may be needed when a valgus knee position is required to manage the medial meniscus tear

Pulmonary hypertension in obstructive sleep apnea hypopnea syndrome

Background: There has been uncertainty until recently whether OSA, is sufficient to cause persistent daytime pulmonary hypertension and right ventricular dysfunction. Objectives: The aims of this study, were to investigate whether OSA by itself without any other cardiac or lung disease can lead to pulmonary hypertension, and to assess the effect of CPAP therapy on pulmonary artery pressure. Subjects and methods: The study was performed on 54 OSA patients. All patients were subjected to thorough history taking including Epworth sleepiness scale and Berlin questionnaire, physical examinations, calculation of BMI, plain chest X-ray pulmonary function tests, polysomnography and echocardiography. Ten patients out of 24 patients of OSA with PH have been treated with CPAP for six months. Results: Pulmonary hypertension (PH) was present in (44.4%) of OSA patients. There were significantly higher PASP and mPAP in severe OSA patients versus non severe OSA patients. There were significant higher BMI, neck circumference, AHI and ODI in OSA patients with PH compared to OSA patients without PH. Awake SaO2 and minimum SaO2 were significantly lower in OSA patients with PH compared to OSA patients without PH. There were significant reduction in both mPAP and PASP after 6 months of CPAP treatment (p = 0.007, 0.005 respectively). Conclusion: OSA is associated with pulmonary hypertension, improvement of pulmonary hypertension through controlling OSA by CPAP therapy signifies that OSA plays a crucial role in the pathogenesis of pulmonary hypertension. Recommendations: CPAP therapy should be advised to all OSA patients with pulmonary hypertension

Assessment of interleukin-6 role in detecting coronavirus disease 2019 severity, mortality, and its control: A cohort study

Background Elevated serum level of interleukin-6 (IL-6) in patients with coronavirus disease 2019 (COVID-19) may be a result of a cytokine storm and can be an indicator of severe and critical forms of the disease.Therefore, it is crucial to detect and control IL-6 level early in severe acute respiratory syndrome coronavirus-2-infected patients; in addition to that, IL-6 may be a target for drug development. Aim In this study, we aimed to evaluate IL-6 serum levels in severe acute respiratory syndrome coronavirus-2-infected patients with positive PCR result early after diagnosis to detect disease severity and mortality. Study design and methods This prospective study was done on 60 COVID-19-infected patients. Serum IL-6 levels were tested after diagnosis. Tocilizumab was given to 11 patients with severe COVID-19. Results High serum levels of IL-6 had been detected in 95% of patients and in all patients of the critical group. Its levels in the mild group were 1.87 times less than that in the moderate group, whereas 2.85 times less than that in the critical group. IL-6 median levels were 24, 44.85, and 68.4 ng/l for the mild, moderate, and critical groups, respectively. The IL-6 concentration was predictive of severity (with IL-6 cutoff value >56 ng/l) and was predictive of mortality (with a cutoff value >67 ng/l) for COVID-19-infected patients. Tocilizumab cure rate was 30% in critical cases. Conclusion Serum IL-6 is of paramount importance in detecting severity and mortality of COVID-19 disease, whereas therapeutic value of tocilizumab needs confirmation by detailed studies