Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents
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99 GENERAL AND MISCELLANEOUS↗
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Results for “CEREBROSPINAL FLUID”
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HIV influences microtubule associated protein-2: potential marker of HIV-associated neurocognitive disorders
Postmortem brains of patients diagnosed with HIV-1-associated neurocognitive disorders (HAND) exhibit loss of dendrites. However, the mechanisms by which synapses are damaged are not fully understood. Dendrite length and remodeling occurs via microtubules, the dynamics of which are regulated by microtubule-binding proteins, including microtubule-associated protein 2 (MAP2). The HIV protein gp120 is neurotoxic and interferes with neuronal microtubules. We measured MAP2 concentrations in human cerebrospinal fluid (CSF) and MAP2 immunoreactivity in rat cortical neurons exposed to HIV and gp120. First, we examined whether HIV affects MAP2 levels by analyzing the CSF of 27 persons living with HIV (PLH) whose neurocognitive performance had been characterized. We then used rat cortical neurons to study the mechanisms of HIV-mediated dendritic loss. PLH who had HAND had greater MAP2 concentrations within the CSF than cognitive normal PLH. In cortical neurons, the deleterious effect of HIV on MAP2-positive dendrites occurred through a gp120-mediated mechanism. The neurotoxic effect of HIV was blocked by a CCR5 antagonist and prevented by Helix-A, a peptide that displaces gp120 from binding to microtubules, conjugated to a nanolipoprotein particle delivery platform. Our findings support that HIV at least partially effects its neurotoxicity via neuronal cytoskeleton modifications and provide evidence of a new therapeutic compound that could be used to prevent the HIV-associated neuropathology.
60 APPLIED LIFE SCIENCES↗
Implementation of rapid diagnostics assays for detection of histoplasmosis and cryptococcosis in central american people living with HIV
Abstract Objectives Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. Methods Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). Results A total of 4,453 PLHIV with clinical suspicion of histoplasmosis ( n = 1,343) or cryptococcosis ( n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay ( n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay ( n = 170). Conclusion Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.
Caceres, Diego H.↗
Multi-Species Complex and Standard Metabolomic Samples with Verified Truth Annotations Dataset
This dataset contains 4523251 (~6.35 GB) metabolite-spectra matches following identification with CoreMS. Data were manually curated as true positives, true negatives, or unknowns. Calculations for spectral similarity scores were carried out with two methods for a total of ~12.7 GB (6.35 * 2) of data. They are all .tsv files, though can easily be changed to .txt. The file types are: * human cerebrospinal fluid (CSF), human blood plasma human urine: already published here https://www.nature.com/articles/s41597-021-00894-y, • purchased FAMES standards • fungi species (A. niger, A. nidulans, T. reesei) • soil crust
59 BASIC BIOLOGICAL SCIENCES↗
Genomic surveillance indicates clonal replacement of hypervirulent Klebsiella pneumoniae ST881 and ST29 lineage strains in vivo
The emergence of hypervirulent Klebsiella pneumoniae (hvKp) poses a significant public health threat, particularly regarding its carriage in the healthy population. However, the genomic epidemiological characteristics and population dynamics of hvKp within a single patient across distinct infection episodes remain largely unknown. This study aimed to investigate the clonal replacement of hvKp K2-ST881 and K54-ST29 lineage strains in a single patient experiencing multiple-site infections during two independent episodes. Two strains, designated EDhvKp-1 and EDhvKp-2, were obtained from blood and cerebrospinal fluid during the first admission, and the strain isolated from blood on the second admission was named EDhvKp-3. Whole-genome sequencing, utilizing both short-read Illumina and long-read Oxford Nanopore platforms, was conducted. In silico multilocus sequence typing (MLST), identification of antimicrobial resistance and virulence genes, and the phylogenetic relationship between our strains and other K. pneumoniae ST881 and ST29 genomes retrieved from the public database were performed. Virulence potentials were assessed through a mouse lethality assay. Our study indicated that the strains were highly susceptible to multiple antimicrobial agents. Plasmid sequence analysis confirmed that both virulence plasmids, pEDhvKp-1 (166,008 bp) and pEDhvKp-3 (210,948 bp), belonged to IncFIB type. Multiple virulence genes, including rmpA , rmpA2 , rmpC , rmpD , iroBCDN , iucABCD , and iutA , were identified. EDhvKp-1 and EDhvKp-2 showed the closest relationship to strain 502 (differing by 51 SNPs), while EDhvKp-3 exhibited 69 SNPs differences compared to strain TAKPN-1, which all recovered from Chinese patients in 2020. In the mouse infection experiment, both ST881 EDhvKp-1 and ST29 EDhvKp-3 displayed similar virulence traits, causing 90 and 100% of the mice to die within 72 h after intraperitoneal infection, respectively. Our study expands the spectrum of hvKp lineages and highlights genomic alterations associated with clonal switching between two distinct lineages of hvKP that successively replaced each other in vivo . The development of novel strategies for the surveillance, diagnosis, and treatment of high-risk hvKp is urgently needed.
Liu, Ning↗
Digital simulation and experimental evaluation of the CO2-H(plus) control of pulmonary ventilation
Previous models of the CO2-H(+) control of ventilation have been concerned either with the response to CO2 inhalation, or the response to perfusion of the surface of the medulla with mock cerebrospinal fluid having a high P sub CO2. Simulation of both responses with the same model has not been attempted. The purpose of the present study was two fold; first to develop such a model and, second, to obtain experimental data from human subjects for both developing this model and for evaluating this and future models.
Milhorn, H. T., Jr.↗
Intrathoracic and venous pressure relationships during responses to changes in body position
Simultaneous end-expiratory pressures, referred to midthoracic level, in the superior and abdominal venae cavae, pericardial space, and right and left heart, were recorded without thoracotomy in three anesthetized dogs during sudden changes from supine to vertical head-up or head-down body positions. Intrathoracic and dependent great vein pressures referred to midchest level (sixth thoracic vertebra) decreased and showed simple hydrostatic gradients in either vertical position. However, a discontinuity in the large vein hydrostatic gradient occurred just distal to the superior margin of the thorax in either body position and was resumed again above this level. It is concluded that, just as the cerebrospinal fluid and intraperitoneal pressures minimize the effects of gravitational and inertial forces on the cerebral and visceral circulations, the pericardial and pleural pressures have a similar role for the heart proper.
Avasthey, P.↗
Effects of subfornical organ extracts on salt-water balance in the rat
The subfornical organ (SFO) is a circumventricular structure located at the junction of the lamina terminalis and the tela choroidea of the third cerebral ventricle. SFO is histologically regarded as a neurosecretory structure, although the physiological effects or biochemical nature of such secretions are not yet ascertained. Results are presented for an experimental study designed to determine whether SFO extracts alter parameters associated with salt-water balance in the rat. The data obtained support the conclusion that SFO contains some water-soluble substance(s), easily released by incubation, dialyzable and heat stable, which influences the salt-water balance after injection into ventricular cerebrospinal fluid. Whether other brain tissues or plasma contains the same or similar material is not yet convincingly established. The observation that one or more active constituents are easily released from SFO upon incubation in potassium-enriched medium may be of value.
Summy-Long, J. Y.↗
Idiopathic orthostatic hypotension: Recent data (eleven cases) and review of the literature
Eight cases of Shy-Drager syndrome and three of Bradbury-Eggleston idiopathic orthostatic hypotension were examined. In all cases, examination of circulatory reflexes showed major dysfunction of the sympathetic vasoconstrictor system. Anomalies in the vagal cardiomoderator system were less constant. Normal urinary elimination of catecholamines was recorded daily. Characteristically, no elevation of blood or urine norepinephrine levels were found in orthostatism. Insulin hypoglycemia normally raised urinary adrenalin elimination in three of ten patients. Plasma dopa-beta-hydroxylase activity was normal. Renin-angiotensin-aldosterone system showed variable activity at basal state but usually rose during orthostatism. On the average, very low homovanillic acid levels were found in cerebrospinal fluid before and after probenecid; hydroxyindolacetic acid was normal. Cerebral autoregulation had deteriorated in two of four cases. Physiopathologically the two clinical types are indistinguishable with or without central neurological signs.
Ninet, J.↗
Method of making an ion beam sputter-etched ventricular catheter for hydrocephalus shunt
The centricular catheter comprises a multiplicity of inlet microtubules. Each microtubule has both a large opening at its inlet end and a multiplicity of microscopic openings along its lateral surfaces. The microtubules are perforated by an ion beam sputter etch technique. The holes are etched in each microtubule by directing an ion beam through an electro formed mesh mask producing perforations having diameters ranging from about 14 microns to about 150 microns. This structure assures a reliable means for shunting cerebrospinal fluid from the cerebral ventricles to selected areas of the body.
Banks, B. A.↗
Neural mechanisms of motion sickness
The possibility that there might be a neuro-homoral cerebrospinal fluid link in motion sickness was directly tested by blocking the flow of CSF from the third into the fourth ventricle in cats. Evidence obtained thus far is consistent with the hypothesis. Cats with demonstrably sound plugs did not vomit in response to an accelerative motion sickness stimulus, whereas cats with imperfect 'leaky' plugs vomited with little or no delay in latency. Althoough there are several putative candidates, the identification of a humoral motion sickness substance is a matter of conjecture.
Crampton, G. H.↗
Vasopressin and motion sickness in cats
Levels of arginine vasopressin (AVP) in blood plasma and cerebrospinal fluid (CSF) were measured in cats under several motion-sickness-inducing conditions. Plasma AVP increased significantly in both susceptible and resistant animals exposed to motion. When vomiting occurred, levels of plasma AVP were drmatically elevated (up to 27 times resting levels). There was no difference in resting levels of AVP of susceptible and resistant cats. Levels of CSF-AVP were not elevated immediately after vomiting, but the testing levels of CSF-AVP were lower in animals that vomited during motion than in those animals which did not vomit during motion. The results of these experiments show that changes in systemic AVP are directly related to vomiting induced by motion, however, CSF-AVP apparently does not change in association with vomiting. CSF-AVP does appear to be lower in animals that reach frank vomiting during motion stimulation than in animals which do not vomit.
Fox, R. A.↗
Serotonergic mechanisms in emesis
The observation that the cerebrospinal fluid of cats which are susceptible to motion sickness contained lower baseline levels of 5-hydroxyindoleacetic acid, among other constituents, led to the hypothesis that serotonin inhibits emesis. The hypothesis was tested by administration of the serotonin-1A agonists buspirone and 8-OH-DPAT before motion testing in cats susceptible to motion sickness. Both drugs blocked motion sickness in a dose-dependent fashion. To determine if these drugs blocked emesis elicited by other stimuli, they were administered before subcutaneous administration of the alpha-2 noradrenergic agonist, xylazine. Both drugs also blocked xylazine-induced emesis. It was concluded that the stimulation of serotonin-1A receptors inhibits emesis elicited by the two stimuli and that this mechanism may exert a general antiemetic effect.
Lucot, J. B.↗
Pharmacological and neurophysiological aspects of space/motion sickness
A motorized motion testing device modeled after a Ferris wheel was constructed to perform motion sickness tests on cats. Details of the testing are presented, and some of the topics covered include the following: xylazine-induced emesis; analysis of the constituents of the cerebrospinal fluid (CSF) during motion sickness; evaluation of serotonin-1A (5-HT sub 1A) agonists; other 5HT receptors; antimuscarinic mechanisms; and antihistaminergic mechanisms. The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists, peptides, cannabinoids, cognitive enhancers (nootropics), dextromethorphan/sigma ligands, scopolamine, and diphenhydramine.
Lucot, James B.↗
A comparison of neural network and fuzzy clustering techniques in segmenting magnetic resonance images of the brain
Magnetic resonance (MR) brain section images are segmented and then synthetically colored to give visual representations of the original data with three approaches: the literal and approximate fuzzy c-means unsupervised clustering algorithms and a supervised computational neural network, a dynamic multilayered perception trained with the cascade correlation learning algorithm. Initial clinical results are presented on both normal volunteers and selected patients with brain tumors surrounded by edema. Supervised and unsupervised segmentation techniques provide broadly similar results. Unsupervised fuzzy algorithms were visually observed to show better segmentation when compared with raw image data for volunteer studies. However, for a more complex segmentation problem with tumor/edema or cerebrospinal fluid boundary, where the tissues have similar MR relaxation behavior, inconsistency in rating among experts was observed.
Hall, Lawrence O.↗
Melatonin concentrations in the sudden infant death syndrome
To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean plus or minus S.E.M., 2.6 plus or minus 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 plus or minus 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 plus or minus 29 pmol/l; n = 32) than among those dying from other causes (180 plus or minus 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 plus or minus 23, n = 30 vs. 144 plus or minus 22 pmol/l, n = 33) and vitreous humor (68 plus or minus 21, n = 10 vs. 81 plus or minus 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection, or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.
Sturner, W. Q.↗
Measuring Intracranial Pressure And Volume Noninvasively
Ultrasonic technique eliminates need to drill into brain cavity. Intracranial dynamics instrument probes cranium ultrasonically to obtain data for determination of intracranial pressure (ICP) and pressure-volume index (PVI). Instrument determines sensitivity of skull to changes in pressure and by use of mechanical device to exert external calibrated pressure on skull. By monitoring volume of blood flowing into jugular vein, one determines change of volume of blood in cranial system. By measuring response of skull to increasing pressure (where pressure increased by tilting patient known amount) and by using cranial blood pressure, one determines intial pressure in cerebrospinal fluid. Once PVI determined, ICP determined.
Cantrell, John H.↗
Subacute diabetic proximal neuropathy
OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved, but such intervention may be considered in the severe and progressive cases or ones associated with severe neuropathic pain.
Non-NASA Center↗