Suspected Conn's Syndrome in A Female Adult Hypertensive: A Case Report.

Background: The presentation of adrenal adenoma with ventricular fibrillation and sudden death is rare. Ventricular fibrillation is the most common cause of sudden death. Coronary artery disease, cardiac valvular or myocardial diseases, and non -cardiac abnormalities may also lead to ventricular fibrillation. We present a patient with recurrent ventricular fibrillation and associated adrenal tumour.Methods: The case records of the index patient and a review of the literature on the subject.Result: A 39 year old hypertensive woman presented in the accident and emergency department of the University of Port-Harcourt Teaching Hospital with a history of extreme weakness and inability to walk of four day duration. While being evaluated, she had a cardiac arrest and was successfully resuscitated. She had two more episodes of cardiac arrest in the Intensive care unit. Investigations revealed ventricular fibrillation from ventricular tachycardia and severe hypokalaemia with metabolic alkalosis. Abdominal CT scan revealed a right adrenal mass. ACTH level, serum and urinary cortisol levels were normal. A diagnosis of Conn's syndrome was made and patient did well on spironolactone and other antihypertensives as she awaits surgery.Conclusion : There is a need for high index of suspicion for the secondary causes of hypertension while dealing with young patients and whenever there is an unusual presentation. This case highlights the need for proper investigation of patients.Key Words: Conn's syndrome; Cardiac Arrest; Adrenal tumor; Nigerian Female

Characterizing Migratory Signaling Pathways Of Transplantable Retinal Progenitor Cells And Photoreceptor Precursor Cells Toward Restoration Of Degenerative Retina \u27 A Systems Biology Approach

A common feature of several heterogeneous diseases that result in retinal degeneration (RD) is photoreceptor loss, leading to an irreversible decline in visual function [15-17]. There are no cell replacement treatments available for RD diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Although many RD cases are of a genetic origin, a promising strategy to treat diseased phenotypes is by replacing lost photoreceptor cells, for synaptic integration and restoration of visual function. To advance photoreceptor-replacement strategies as a practical therapy, in light of highly restricted integration rates reported across studies, this body of research focused on defining the molecular mechanisms facilitating migration of transplantable photoreceptor precursors in the retinal microenvironment. To accomplish this work we utilized bioinformatics, bioengineering and molecular biologic techniques for a systems level approach. Guided by classic neuronal migration models, we hypothesized that transplanted photoreceptor precursors navigate to specific retinal lamina in part due to cell surface receptor expression and in response to spatially gradated directional ligand cues provided by the host retinal microenvironment. Given the neural origin of the mammalian retinal system, we also predicted that these chemotactic receptor-ligand pairs trigger intracellular signaling events in migrating photoreceptors analogous to canonical migration pathways exhibited by neuronal precursors. For a comprehensive account of these motility-deterministic biochemical interactions, we first performed in silico bioinformatics modeling of PPC transplantation into light-damaged retina by matching microarray datasets between PPC receptors and ligands in the light-damaged retinal microenvironment. We then refined the gene expression network data to focus on motility deterministic interactions at the interface of the PPC cell-surface receptors and extracellular ligands of the damaged retina. Our in silico network modeling generated a library of ligand-receptor pairs associated with cellular movement specific for this retinal transplantation paradigm and the intracellular signaling pathways induced by candidate chemotactic ligands. Working from predicted interactions of in silico paired PPC receptors and retinal ligands, we then performed cell migration analysis to evaluate whether exposure to stromal derived factor-1α (SDF-1α) would guide the motility of PPCs and RPCs in vitro. We also assessed the chemotactic effects of epidermal growth factor (EGF) on RPCs. Cell surface expression of C-X-C chemokine receptor type 4 (CXCR4) receptors on PPCs and RPCs, and EGF receptor expression on RPCs were verified via immunocytochemical staining and validated by Western blot analysis. Boyden chamber analysis was used as an initial high-throughput screen to verify the motogenic effects of the ligands on PPCs and RPCs. We determined that RPC motility was optimally stimulated in these chambers by EGF concentrations in the range of 20-400ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGF-induced motility. Both RPCs and PPCs also demonstrated a concentration-dependent chemotactic response to an optimal SDF-1α concentration of 100ng/ml. Using bioinformatics downstream signaling pathway analysis of the EGF and SDF-1α ligands in a retina-specific gene network, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways. Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3Kinase signaling pathways are necessary to drive RPC motility. The JAK-STAT pathway was also implicated in transducing similar motogenic effects on PPCs with SDF-1α induction. To test our hypothesis of the gradated nature of ECM ligand effects on both ontogenetic retinal cell types, we employed engineered microfluidic devices to generate quantifiable steady-state gradients of EGF and SDF-1α coupled with live-cell tracking, and analyzed the dynamics of individual RPC and PPC motility. Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic in EGFR expressing RPCs with optimal activity observed in response to low concentration gradients. On the other hand, PPCs and RPCs exhibited significant chemotaxis towards the source of SDF-1α with longer accumulated Euclidean distances and Center of Mass (COM) compared to controls. We also ascertained that receptor mediated signaling was requisite for ligand-induced motility by using the CXCR4 inhibitor, AMD 3100, to antagonize the SDF-1α receptor. CXCR4 receptor inhibition resulted in decreases of PPC and RPC movement in uniform and steady state gradients for a number of migration indices measured. To advance translational application of the characterized chemotactic signaling potential of transplantable photoreceptor precursors, we performed computational drug analysis of our newly identified motility-deterministic networks, to develop a library of FDA approved drugs and small molecules predicted to potentially influence the expression of target motility signaling mechanisms in photoreceptor progenitor cells. Using the Expression2Kinases software and LINCS drug computational algorithm, we were able to identify pharmacological drug targets that modulate the biochemical activity of transcriptional regulatory genes which govern the expression of candidate receptor protein targets, and provide preliminary results validating the up-regulatory effect of candidate drug aminophenazone on SDF-1α receptor CXCR4 expression. Results from this study demonstrate the applicability of our systems level in silico modeling of matched transplantable cell surface-receptors and transplantation site ligands to predict molecular signaling guiding migration. Verification of in silico predictions, using molecular and microfluidic analysis provide important data for defining cell response properties to specific ligands present during transplantation into the retinal microenvironment. The drug computational analysis provides a translational perspective to our in silico modeling paradigms extending its applicability. Future studies will validate the functionality of resolved ligand-receptor pairs from our in silico library and characterize down-stream signaling guiding motility and homing. This systems level paradigm can effectively be applied to defining the molecular basis of transplantable cell migration in vivo toward improved efficiency for repair of retina and other neural tissue types

Mortality among Diabetes In-Patients in Port-Harcourt, Nigeria

Background: Diabetes mellitus is a major cause of mortality and morbidity among in-patients in Nigeria. It may result from the acute metabolic complications or from the inexorable effects of chronic complications in the major organ systems. Objectives: This study was to determine the death rates and causes of death among in-patients with diabetes at an urban tertiary hospital in Port-Harcourt. Materials and Methods: The medical records of patients admitted with diabetes mellitus into the medical wards of the University of Port Harcourt Teaching Hospital from 1995-2004 were reviewed. The sources of data were the ward admission, death registers, death certificates and medical records. The annual and overall fatality rates were calculated from the available data. Results: During the period under review, 6,574 patients were admitted into the medical wards. Out of these, 686 (10.4%) were due to diabetes and its complications. The diabetic patients comprised of 428 (62.4%) males and 258 (37.6%) females giving a M:F ratio of 1.7:1. One hundred and eighteen of the diabetic patients died giving a case fatality of 17.2%. The main causes of death were diabetic ketoacidosis (DKA) (21.2%), diabetic mellitus foot syndrome (DMFS) (19.5%) and renal failure (12.7%). Diabetic emergencies accounted for 39.8% of all deaths. Conclusion: Diabetes mellitus is a significant cause of medical admissions in Port-Harcourt. The case mortality is very high especially from acute metabolic causes. There is a need for improved management of diabetes in Nigeria. Keywords: Mortality, Diabetes in-patients, Niger Delta

Situs Inversus in A 53 Year Old Man: A Case Report

Background: Total or complete visceral situs inversus is the complete inversion of position of the thoracic and abdominal viscera. It may be isolated or associated with malformations, especially cardiac or alimentary. It may be discovered in infancy because of associated anomalies but often remains asymptomatic and discovered by chance in adult life.Method: The case records of the index patient and literature review on the subject were utilized.Result: A 53 year old man was referred to the cardiology clinic from the general outpatient department on account of an abnormal ECG. On examination his apex could not be located on the left and was subsequently located on the right 5th intercostal space mid-clavicular line. Examination of the abdomen revealed an inversion of position of the liver and spleen. Chest X-ray showed the heart in the right hemithorax with the cardiac apex pointing to the right, the aortic arch and gastric air bubble were located on the right as well. Lungs and thoracic cage were normal. Echocardiography showed a mirror image dextrocardia. While electrocardiography revealed inverted P waves in lead 1 with predominantly downward QRS complexes in leads 1, V and V . 5 6 Abdominal scan showed mirror-image anatomy of the abdominal viscera.Conclusion: Situs inversus totalis though a rare condition, should be sought for when clinical and radiologic findings indicate dextrocardia, especially as it may be an incidental finding.Key Words: Dextrocardia; Situs Inversus; Totalis; Nigerian male

Microfluidic Generated EGF-Gradients Induce Chemokinesis of Transplantable Retinal Progenitor Cells via the JAK/STAT and PI3Kinase Signaling Pathways

A growing number of studies are evaluating retinal progenitor cell (RPC) transplantation as an approach to repair retinal degeneration and restore visual function. To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility. We have analyzed RPC expression of the epidermal growth factor receptor (EGFR) and evaluated whether exposure to epidermal growth factor (EGF) can coordinate motogenic activity in vitro. Using Boyden chamber analysis as an initial highthroughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGFinduced motility. Using bioinformatics analysis of the EGF ligand in a retina-specific gene network pathway, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways. Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3kinase signaling pathways are necessary to drive RPC motility. Using engineered microfluidic devices to generate quantifiable steady-state gradients of EGF coupled with live-cell tracking, we analyzed the dynamics of individual RPC motility. Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic with optimal activity observed in response to low concentration gradients. Our combined results show that EGFR expressing RPCs exhibit enhanced chemokinetic motility in the presence of low nanomole levels of EGF. These findings may serve to inform further studies evaluating the extent to which EGFR activity, in response to endogenous ligand, drives motility and migration of RPCs in retinal transplantation paradigms

Chemotactic Migration of Clustered Central Nervous System Progenitor Cells

Clustering of central nervous system (CNS) cells is often utilized for cell growth and characterization, as well as investigated for tissue regeneration and disease progression. Collective CNS cell migration, however, has been largely unstudied. Cell cluster formation and migration play a critical part of modeling in vivo conditions and in development of therapies. Three distinct CNS cell types, medulloblastoma (MB), medulloblastoma-derived glial progenitor cells (MGPC), and retinal progenitor cells (RPC), were investigated for cluster formation, upregulation of CXCR4, the receptor for Stromal-Derived Growth Factor (SDF-1), and Connexin 43 expression, a gap junction hemichannel. A microfluidic platform was used to examine the the migration of clusters and single cells in response to controlled concentration gradients of SDF-1. All cell types illustrated self-clustering, as well as upregulated CXCR4 surface expression and increased Connexin 43 expression upon ligand stimulation. Further, RPC clusters exhibited collective, chemotactic migration along SDF-1 concentration gradients, while MB clusters illustrated inconsistent collective migration, and MGPCs clusters did not exhibit adhesion-based migration

In vitro formation of neuroclusters in microfluidic devices and cell migration as a function of stromal-derived growth factor 1 gradients

Central nervous system (CNS) cells cultured in vitro as neuroclusters are useful models of tissue regeneration and disease progression. However, the role of cluster formation and collective migration of these neuroclusters to external stimuli has been largely unstudied in vitro. Here, 3 distinct CNS cell types, medulloblastoma (MB), medulloblastoma-derived glial progenitor cells (MGPC), and retinal progenitor cells (RPC), were examined with respect to cluster formation and migration in response to Stromal-Derived Growth Factor (SDF-1). A microfluidic platform was used to distinguish collective migration of neuroclusters from that of individual cells in response to controlled concentration profiles of SDF-1. Cell lines were also compared with respect to expression of CXCR4, the receptor for SDF-1, and the gap junction protein Connexin 43 (Cx43). All cell types spontaneously formed clusters and expressed both CXCR4 and Cx43. RPC clusters exhibited collective chemotactic migration (i.e. movement as clusters) along SDF-1 concentration gradients. MGPCs clusters did not exhibit adhesion-based migration, and migration of MB clusters was inconsistent. This study demonstrates how controlled microenvironments can be used to examine the formation and collective migration of CNS-derived neuroclusters in varied cell populations

Effects of Extreme Climate Events on Tea (Camellia sinensis) Functional Quality Validate Indigenous Farmer Knowledge and Sensory Preferences in Tropical China

Climate change is impacting agro-ecosystems, crops, and farmer livelihoods in communities worldwide. While it is well understood that more frequent and intense climate events in many areas are resulting in a decline in crop yields, the impact on crop quality is less acknowledged, yet it is critical for food systems that benefit both farmers and consumers through high-quality products. This study examines tea (Camellia sinensis; Theaceae), the world’s most widely consumed beverage after water, as a study system to measure effects of seasonal precipitation variability on crop functional quality and associated farmer knowledge, preferences, and livelihoods. Sampling was conducted in a major tea producing area of China during an extreme drought through the onset of the East Asian Monsoon in order to capture effects of extreme climate events that are likely to become more frequent with climate change. Compared to the spring drought, tea growth during the monsoon period was up to 50% higher. Concurrently, concentrations of catechin and methylxanthine secondary metabolites, major compounds that determine tea functional quality, were up to 50% lower during the monsoon while total phenolic concentrations and antioxidant activity increased. The inverse relationship between tea growth and concentrations of individual secondary metabolites suggests a dilution effect of precipitation on tea quality. The decrease in concentrations of tea secondary metabolites was accompanied by reduced farmer preference on the basis of sensory characteristics as well as a decline of up to 50% in household income from tea sales. Farmer surveys indicate a high degree of agreement regarding climate patterns and the effects of precipitation on tea yields and quality. Extrapolating findings from this seasonal study to long-term climate scenario projections suggests that farmers and consumers face variable implications with forecasted precipitation scenarios and calls for research on management practices to facilitate climate adaptation for sustainable crop production

Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment

Characterization of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology and Pluripotent Content

Microvesicles (MVs) are lipid bilayer-covered cell fragments that range in diameter from 30 nm–1uM and are released from all cell types. An increasing number of studies reveal that MVs contain microRNA, mRNA and protein that can be detected in the extracellular space. In this study, we characterized induced pluripotent stem cell (iPSC) MV genesis, content and fusion to retinal progenitor cells (RPCs) in vitro. Nanoparticle tracking revealed that iPSCs released approximately 2200 MVs cell/hour in the first 12 hrs with an average diameter of 122 nm. Electron and light microscopic analysis of iPSCs showed MV release via lipid bilayer budding. The mRNA content of iPSC MVs was characterized and revealed the presence of the transcription factors Oct-3/4, Nanog, Klf4, and C-Myc. The protein content of iPSCs MVs, detected by immunogold electron microscopy, revealed the presence of the Oct-3/4 and Nanog. Isolated iPSC MVs were shown to fuse with RPCs in vitro at multiple points along the plasma membrane. These findings demonstrate that the mRNA and protein cargo in iPSC MVs have established roles in maintenance of pluripotency. Building on this work, iPSC derived MVs may be shown to be involved in maintaining cellular pluripotency and may have application in regenerative strategies for neural tissue