Search

Background Though decreasing in incidence and mortality in the USA, lung cancer remains the deadliest of all cancers. For a significant number of patients, the emergency department (ED) provides the first pivotal step in lung cancer prevention, diagnosis, and management. As screening recommendations and treatments advance, ED providers must stay up-to-date with the latest lung cancer recommendations. The purpose of this review is to identify the many ways that emergency providers may intersect with the disease spectrum of lung cancer and provide an updated array of knowledge regarding detection, management, complications, and interdisciplinary care. Findings Lung cancer, encompassing 10–12% of cancer-related emergency department visits and a 66% admission rate, is the most fatal malignancy in both men and women. Most patients presenting to the ED have not seen a primary care provider or undergone screening. Ultimately, half of those with a new lung cancer diagnosis in the ED die within 1 year. Incidental findings on computed tomography are mostly benign, but emergency staff must be aware of the factors that make them high risk. Radiologic presentations range from asymptomatic nodules to diffuse metastatic lesions with predominately pulmonary symptoms, and some may present with extra-thoracic manifestations including neurologic. The short-term prognosis for ED lung cancer patients is worse than that of other malignancies. Screening offers new hope through earlier diagnosis but is underutilized which may be due to racial and socioeconomic disparities. New treatments provide optimism but lead to new complications, some long-term. Multidisciplinary care is essential, and emergency medicine is responsible for the disposition of patients to the appropriate specialists at inpatient and outpatient centers. Conclusion ED providers are intimately involved in all aspects of lung cancer care. Risk factor modification and referral for lung cancer screening are opportunities to further enhance patient care. In addition, with the advent of newer cancer therapies, ED providers must stay vigilant and up-to-date with all aspects of lung cancer including disparities, staging, symptoms of disease, prognosis, treatment, and therapy-related complications.

Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle. This metabolic reprogramming was linked with reduced expression of p53 pathway genes that mediate apoptosis and ferroptosis, as well as preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis, while metabolically sensitive redox drivers of ferroptosis were also reduced. Overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obesedb/dbmice enhanced oxidative capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of the oxidative state of skeletal muscle, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ42. Increasing circulating Aβ42 levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ40 isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42 inhibited mitochondrial function. These data reveal a role for systemic Aβ42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.

Root hemiparasites acquire resources from neighboring plants' vascular systems and can limit host growth, depress community productivity, and exert keystone effects. The strength of these effects is posited to be greater where hosts are nutrient-stressed but studies of annual hemiparasites show effects to be short-lived and variable. We conducted a 10-year experiment testing whether fertilizer addition alters the impact of the clonal, perennial hemiparasite Pedicularis canadensis on a prairie community and examine whether short-term trends reflect longer-term effects on community dynamics. Hemiparasite removal in 1-m2 plots increased productivity over the first three field seasons, but later the difference between removal and non-removal plots diminished as P. canadensis disappeared from 24 of the 48 non-removal plots. Effects of hemiparasite removal were context independent relative to fertilizer and shade treatments, but fertilizer initially increased, and then subsequently suppressed P. canadensis biomass. In non-removal plots, hemiparasite biomass was negatively associated with total community dry mass, which was greater in fertilized plots. Initially, fertilizer promoted graminoids, but after seven more field seasons, non-legume forbs responded most strongly. Measures of biodiversity tended to increase with hemiparasite cover. Demographic data collected at two different times for P. canadensis show high survivorship of established plants, high seed input, with seedling survival greater in taller vegetation. Unlike annual hemiparasite populations, well-established P. canadensis buffer populations against large demographic swings. At the scale of a few square meters, this keystone species produces significant heterogeneity in a prairie, but its presence at that scale is transient over approximately one decade.

By means of a particle-in-cell (PIC) simulation, we study the interaction between a uniform magnetized ambient electron-proton plasma at rest and an unmagnetized pair plasma, which we inject at one simulation boundary with a mildly relativistic mean speed and temperature. The magnetic field points out of the simulation plane. The injected pair plasma expels the magnetic field and piles it up at its front. It traps ambient electrons and drags them across the protons. An electric field grows, which accelerates protons into the pair cloud's expansion direction. This electromagnetic pulse separates the pair cloud from the ambient plasma. Electrons and positrons, which drift in the pulse's nonuniform field, trigger an instability that disrupts the current sheet ahead of the pulse. The wave vector of the growing perturbation is orthogonal to the magnetic field direction and magnetic tension cannot stabilize it. The electromagnetic pulse becomes permeable for pair plasma, which forms new electromagnetic pulses ahead of the initial one. A transition layer develops with a thickness of a few proton skin depths, in which protons and positrons are accelerated by strong electromagnetic fields. Protons form dense clumps surrounded by a strong magnetic field. The thickness of the transition layer grows less rapidly than we would expect from the typical speeds of the pair plasma particles and the latter transfer momentum to protons; hence, the transition layer acts as a discontinuity, separating the pair plasma from the ambient plasma. Such a discontinuity is an important building block for astrophysical pair plasma jets., Accepted for publication in Physics of Plasmas, 13 pages, 15 figures

The endocannabinoid system (ECS) is composed of the endocannabinoid ligands anandamide (AEA) and 2-arachidonoylgycerol (2-AG), their target cannabinoid receptors (CB

Management of pregnancy and delivery in women with lower urinary tract reconstruction is challenging and the currently available literature is insufficient to guide clinical practice. We report pregnancy and delivery outcomes in this specific population.We conducted a national multicenter retrospective study (16 centers) including 68 women with 96 deliveries between 1998 and 2019. These women had at least 1 successful pregnancy and delivery after augmentation enterocystoplasty, catheterizable channel creation and/or artificial urinary sphincter implantation. Maternal and fetal complications during pregnancy and delivery were reported, as well as postpartum functional outcomes, according to the delivery mode. The chi-square test and Student's t-test were used to compare categorical and continuous variables, respectively.Overall 32% of reported pregnancies were complicated by febrile urinary tract infections, 13.5% by renal colic and 14.6% required upper urinary tract diversion. In addition, 10% of patients reported transient self-catheterization difficulties and 13.5% reported de novo or increased urinary incontinence. The preterm delivery rate was 35.3%. Elective C-section was performed in 61% of pregnancies. Twenty complications occurred during delivery (20%), including 19 during elective C-section. Urinary continence at 1 year was unchanged for 93.5% of deliveries. Delivery mode (p=0.293) and multiparity (p=0.572) had no impact on urinary continence.In this population C-section appeared to be associated with a high risk of complications. In the absence of any obstetric or neurological contraindications, vaginal delivery should be proposed as the first line option to the majority of these women.

Models for community invasion can inform grassland management if patterns involving the environment, other species, and invader success are evident. We evaluated unplanned invasion by Lespedeza cuneata into an experiment on a reconstructed tallgrass prairie. Our goal was to determine whether the pattern of invasion by this exotic legume was consistent with either the limiting similarity hypothesis (LSH), which predicts poorer establishment of exotic species in communities with related species, or the biotic resistance hypothesis, which predicts a negative association between species richness and invasion. We also examined how the abiotic environment and hemiparasite abundance affect spread of L. cuneata. From 2006 to 2015 we manipulated fertilizer and presence of the hemiparasitic plant, Pedicularis canadensis, in 1-m2 plots, and manipulated shade for the first 5 years. We found greater support for the LSH. Biomasses of legumes and other forbs in 2008 were negatively associated with change in L. cuneata biomass over the next 7 years but species richness was not a significant effect. Lespedeza cuneata cover in 2015 was lower in fertilized plots relative to unfertilized plots and was negatively associated with a composite variable that described the number and combined cover of legume species and number of exotic species currently in the plots. Shading for five seasons reduced L. cuneata growth, but only significantly in fertilized plots from which the hemiparasite had been removed. Other analysis suggested that L. cuneata increased more as the hemiparasite abundance increased. Prairie management that increases the kinds and abundances of native legume species and increases soil fertility may slow the spread of L. cuneata, but we caution against adding P. canadensis to large areas without greater knowledge of site-specific effects.

We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health follow-up; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.

Solving conservation problems requires students to apply their knowledge of ecology and evolution. We present the Endangered Species Conservation through Habitat Suitability Analysis Laboratory Activity, in which students perform habitat suitability analyses for endangered freshwater species, compelling application of ecological and evolutionary principles. Students gather natural history information for endangered species native to Illinois, synthesize publicly available GIS/map data and habitat requirements for an endangered species, and present evidence-based proposals identifying geographical regions that should be set aside for protection. Students discuss current freshwater conservation issues and develop conceptual understanding of evolution, ecology, and conservation principles and processes. Students are prompted to consider human inclusion in freshwater ecosystems and its consequences. This laboratory investigation is effective in highlighting naïve conceptions of ecology, evolution, and conservation because students are prompted to provide rationale for their management decisions and engage in scientific discourse as they conduct their habitat suitability analyses.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 45 - N° 4 - p. 380-387

Objectifs L’objectif principal de notre etude etait de rapporter les difficultes rencontrees et les complications au cours de la grossesse et de l’accouchement chez les patientes ayant un antecedent de grossesse et d’accouchement apres reconstruction urologique complexe. Methodes Nous avons realise une etude retrospective multicentrique dans 16 centres. Ont ete incluses les patientes aux antecedents d’enterocystoplastie d’agrandissement (EA), et/ou de derivation cutanee continente (DCC), et/ou de sphincter urinaire artificiel (SUA) et ayant presente une grossesse et accouchement. Resultats Soixante-huit femmes ayant presente 96 accouchements entre 1998 et janvier 2019 ont ete incluses. Cinquante pour cent presentaient un dysraphisme spinal, 30 % une lesion medullaire, 15 % une exstrophie vesicale et 6 % une autre pathologie. Cinquante-deux pour cent avaient une EA, 25 % une DCC et 5 % un SUA. Au cours de la grossesse, 10 % ont presente des difficultes d’auto-sondages et 14,6 % ont necessite un drainage du haut appareil urinaire pour colique nephretique ou pyelonephrite aigue. Concernant l’accouchement, le taux de cesarienne etait de 64 % dont 13 % en urgence. Le taux de prematurite etait de 35 %. Un sur 3 des cesariennes se sont compliquees, principalement par lesion de la reconstruction urologique. La continence urinaire a 6 mois de l’accouchement etait non modifiee pour 93,5 % des femmes, quel que soit le mode d’accouchement (p = 0,293) ( Tableau 1 , Tableau 2 , Tableau 3 ). Conclusion A notre connaissance, il s’agit de la plus grosse cohorte rapportant les complications de la grossesse et de l’accouchement apres reconstruction du bas appareil urinaire. La voie basse, lorsqu’elle est possible, doit etre privilegiee en premiere intention, la cesarienne etant a risque de lesion du montage urologique, et ne semblant pas prevenir une incontinence post-partum.

To determine the effect of Scriptaid, a compound that can replicate aspects of the exercise adaptive response through disruption of the class IIa histone deacetylase (HDAC) corepressor complex, on muscle insulin action in obesity.Diet-induced obese mice were administered Scriptaid (1 mg/kg) via daily intraperitoneal injection for 4 weeks. Whole-body and skeletal muscle metabolic phenotyping of mice was performed, in addition to echocardiography, to assess cardiac morphology and function.Scriptaid treatment had no effect on body weight or composition, but did increase energy expenditure, supported by increased lipid oxidation, while food intake was also increased. Scriptaid enhanced the expression of oxidative genes and proteins, increased fatty acid oxidation and reduced triglycerides and diacylglycerides in skeletal muscle. Furthermore, ex vivo insulin-stimulated glucose uptake by skeletal muscle was enhanced. Surprisingly, heart weight was reduced in Scriptaid-treated mice and was associated with enhanced expression of genes involved in oxidative metabolism in the heart. Scriptaid also improved indices of both diastolic and systolic cardiac function.These data show that pharmacological targeting of the class IIa HDAC corepressor complex with Scriptaid could be used to enhance muscle insulin action and cardiac function in obesity.

We present the results of a numerical benchmark study for the MUlti-dimensional Stellar Implicit Code (MUSIC) based on widely applicable two- and three-dimensional compressible hydrodynamics problems relevant to stellar interiors. MUSIC is an implicit large eddy simulation code that uses implicit time integration, implemented as a Jacobian-free Newton Krylov method. A physics based preconditioning technique which can be adjusted to target varying physics is used to improve the performance of the solver. The problems used for this benchmark study include the Rayleigh-Taylor and Kelvin-Helmholtz instabilities, and the decay of the Taylor-Green vortex. Additionally we show a test of hydrostatic equilibrium, in a stellar environment which is dominated by radiative effects. In this setting the flexibility of the preconditioning technique is demonstrated. This work aims to bridge the gap between the hydrodynamic test problems typically used during development of numerical methods and the complex flows of stellar interiors. A series of multi-dimensional tests are performed and analysed. Each of these test cases is analysed with a simple, scalar diagnostic, with the aim of enabling direct code comparisons. As the tests performed do not have analytic solutions we verify MUSIC by comparing to established codes including ATHENA and the PENCIL code. MUSIC is able to both reproduce behaviour from established and widely-used codes as well as results expected from theoretical predictions. This benchmarking study concludes a series of papers describing the development of the MUSIC code and provides confidence in the future applications., Comment: 11 pages, 11 figures, accepted for publication in A&A

Bladder augmentation is commonly used in neurological and other congenital anomalies of the lower urinary tract. In pregnant women, this reconstructive surgery may affect pregnancy and delivery. The obstetrical consequences of these urological procedures are scarcely reported in literature.Eight pregnancies in 6 pregnant women with ileocystoplasty were followed in our institution between 1998 and 2014.Urinary tract infections were the most frequent undesirable record event (5 patients, 7 pregnancies). Obstetrical complications were not more frequent compared to common pregnancies. Delivery was programmed at 37WA. Cesarean section was favoured in this group although natural delivery is possible.Urological complications were the major problem in this series. The type of delivery depends on the past surgical history and the obstetrical prognosis.

During field studies of enzootic Venezuelan equine encephalitis (VEE) viruses associated with epizootic emergence, a large number of virus isolates were made in sylvatic foci of Venezuela and Colombia. To rapidly characterize these isolates, antigenic subtypes were determined by means of immunofluorescence and by single-strand conformational polymorphism (SSCP) analysis by use of an 856-bp fragment from the P62 gene, which we used to distinguish genetic variants. Representative isolates were sequenced to assess the sensitivity of SSCP to detect genetic differences. The SSCP analysis distinguished isolates differing by as little as 1 nucleotide; overall, differences of > or = 1 nucleotide were recognized 89% of the time, and the sensitivity to distinguish strains that differed by only 1 or 4 nucleotides was 17 and 57%, respectively. Phylogenetic analyses of representative sequences showed that all recent isolates from the Catatumbo region of western Venezuela and the middle Magdalena Valley of Colombia were closely related to epizootic subtype IAB and IC strains; strains from Yaracuy and Miranda States were more distantly related. Cocirculation of the same virus genotype in both Colombian and Venezuelan foci indicated that these viruses are readily transported between enzootic regions separated by > 300 km. The SSCP analysis appears to be a simple, fast, and relatively efficient method of screening VEE virus isolates to identify meaningful genetic variants.

The mode of action of the phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on the human immunodeficiency virus 1 (HIV-1) replication in human lymphocytes and monocytes was studied. PDBu and PMA appear to have similar effects on the regulation of HIV-1 replication in acutely infected cells. Here we show a significantly increased replication of HIV-1 induced by PDBu and PMA in Molt-4 and Jurkat cells, but a reduced replication in THP-1 and U-937 cells. Moreover, quantitatively different activity of the two derivatives in relation to HIV-1 replication was observed. PDBu proved to be a stronger stimulator or suppressor of HIV-1 replication as compared to PMA. Although the precise mechanism of the activation of HIV-1 replication by phorbol ester derivatives is not clear, it can be assumed that the hydrophilycity of PDBu may cause its stronger effect.

More than 100 plant extracts from the Amazonian rain forest of Venezuela were evaluated for their cytotoxicity and inhibitory activity against the human immunodeficiency virus type-1 (HIV-1). Aqueous extracts from Fomitella supina (S # 0389-4), Phellinus rhabarbarinus (S # 0389-7), Trichaptum perrottetti (S # 0389-8) and Trametes cubensis (S # 0389-13), Polyporaceae exhibited strong anti-HIV-1 activity, without toxicity for Molt-4 lymphocytic cells. Our results demonstrated, that the compound(s) acted by mechanism of direct virion inactivation and by inhibition of syncytium formation in an in vitro culture system. These results support the suggestion that the test extracts specifically act at the level of CD4-gp120 binding. The active components of these extracts is at present unknown, but anti-AIDS agents, such as those found in this study, individually or in combination, may be of therapeutic relevance.

In order to evaluate central serotonergic function during viral encephalitis biochemical, behavioural and immunohistofluorescence studies were carried out. Mice were inoculated with the moderate virulent strain of Venezuelan equine encephalomyelitis virus, Pixuna. Signs of encephalitis were observed in 50–60% of infected animals. Levels of serotonin and 5-hydroxyindolacetic acid, and the ratio of the indolamine and its metabolite in raphe and cortex did not change with respect to sham-inoculated mice. A differential decrease in turnover rate by pharmacological methods, such as pargyline, p-chlorophenylalanine and probenecid administration, was observed in raphe and cortex. The ratio serotonin turnover rate/steady state concentration of serotonin was only decreased in the raphe of sick animals. The response to 5-methoxy-N, N-dimethyltrypt-amine was greater in infected animals. The duration of immobility in the swim test was shorter in the infected group. A greater number of viral antigen particles was localized in raphe and periraphe areas than in cortex, brain stem or striatum. The results suggest a serotonin presynaptic deficit, a postsynaptic hyperreactivity of serotonin system, and a region-selective distribution of the virus.

In order to evaluate central serotonergic function during viral encephalitis biochemical, behavioural and immunohistofluorescence studies were carried out. Mice were inoculated with the moderate virulent strain of venezuelan equine encephalomyelitis virus, Pixuna. Signs of encephalitis were observed in 50-60% of infected animals. Levels of serotonin and 5-hydroxyindolacetic acid, and the ratio of the indolamine and its metabolite in raphe and cortex did not change with respect to sham-inoculated mice. A differential decrease in turnover rate by pharmacological methods, such as pargyline, p-chlorophenylalanine and probenecid administration, was observed in raphe and cortex. The ratio serotonin turnover rate/steady state concentration of serotonin was only decreased in the raphe of sick animals. The response to 5-methoxy-N,N-dimethyltryptamine was greater in infected animals. The duration of immobility in the swim test was shorter in the infected group. A greater number of viral antigen particles was localized in raphe and periraphe areas than in cortex, brain stem or striatum. The results suggest a serotonin presynaptic deficit, a postsynaptic hyperreactivity of serotonin system, and a region-selective distribution of the virus.

In the framework of Euler flows, I present simulations of wind accretion in well separated binaries for three different cases: Cygnus X-3, a high mass X-ray binary (see e.g. Schmutz et al. 1996), ζ Aurigae, a system showing strong atmospheric eclipse effects (see e.g. Griffin et al. 1990), and the generic barium star model of Theuns and Jorissen (1993), which is recomputed here with a different numerical method (a MUSCL-type integrator, incorporated in our AMRCART code). These simulations represent a first, small sample out of the large parameter space of wind accretion in separated binaries (see Table 1).On the orbital scale, the vorticity of the flow is due to the orbital motion of the stars. It is particularly large for the case where the wind velocity is comparable to the orbital speed of the stars (see Fig. 1). In the vicinity of the accreting star, the vorticity is determined by the accretion process. With two strong vortices above and below the accretor (with respect to the orbital plane), the flow resembles the flow out of a bath tub. On a smaller scale, one finds even more vorticity: The flow is highly turbulent. Such turbulence and the shear flows in the large scale vortices cannot be well captured by an Euler flow model. A next step of improvement would be the use of an appropriate MHD turbulence model.

Pixuna, a strain of intermediate virulence of venezuelan equine encephalomyelitis virus, was inoculated intracranially to 24-day-old mice. Signs of encephalitis were present in 60% of the animals between 6 and 9 days with a maximum at 7 days postinoculation. The rest of the infected mice did not show clinical signs of encephalitis. In order to study the functional state of serotonergic systems a series of tests susceptible to modifications by serotonin activity were carried out. Locomotor activity was measured in an open field test. Virus-inoculated animals presented a variety of changes in their locomotor behavior at various days postinoculation with respect to the sham-inoculated group, however, they were not significant. Central serotonergic function was examined by the production of the serotonergic syndrome with the receptor agonist, 5-methoxy-N,N-dimethyltryptamine and the precursor, 5-hydroxytryptophan, both administered 4 days after the inoculation. The dose of the agonists was established by a prior drug-response analysis. Intensity of the syndrome was significantly higher in infected mice than in the sham-inoculated group only in 5-methoxy-N,N-dimethyltryptamine-treated animals. The behaviour in the swim test was also measured. Duration of immobility was much shorter in infected than in control mice. The decrease in central serotonin turnover previously reported might be responsible for the modification in locomotor behaviour and for the supersensitivity of serotonin receptors observed in infected mice.

Representative strains of Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) were compared for their ability to grow in cultures of unstimulated leucocytes and monocytes derived from donkey peripheral blood. Replication of epizootic and vaccine strains of VEEV, but not of enzootic strains was observed in this system. Only a minority of monocytes supported virus replication as detected by immunofluorescence, electron microscopy and infectious center assays. EEEV did not appear to replicate in this cell system although virus attached to and was internalized by monocytes.

The influence of two strains of Venezuelan equine encephalomyelitis virus on catecholamine metabolism in the central nervous system (CNS) of the mouse was studied by the intracranial inoculation of NMRI-IVIC mice, 24 days old. Doses of 300 LD50 of the moderately virulent Pixuna strain and 10(4) LD50 of the nonvirulent TC-83 strain were used. The animals were sacrificed 4, 7, 12, and 18 days after the inoculation, and the CNS contents of dopamine, norepinephrine, and adrenaline were determined by a radioenzymatic method. The turnover of these compounds was studied with the aid of the enzymatic inhibitors pargyline and alpha-methyl tyrosine. With the Pixuna strain a decrease in the level and turnover of catecholamines was observed in all eight brain areas studied: cerebellum, pons-medulla, hypothalamus, mesencephalon, striatum, olfactory bulb-tuberculum, hippocampus, and cerebral cortex. In some regions the levels returned to normal in 12-18 days, but in the striatum, mesencephalon, hypothalamus, and olfactory bulb-tuberculum, recovery was slower and required at least 18 days after inoculation. The levels of catecholamines in the brain of mice inoculated with the nonvirulent TC-83 strain were not modified, but there was a decrease in the turnover.

Granulomas are chronic, usually focal, tissue-destructive inflammatory reactions that usually form around slowly degradable, poorly soluble substances. They are dynamic lesions, regulated by complex immune mechanisms. Tachykinins are a family of neuropeptides characterized by the common C-terminal amino acid sequence -Phe-X-Gly-Leu-Met-NH2. One such tachykinin, substance P, has been reported to modulate immunologic responses. In this investigation, granulomas were examined for substance P. Granulomas were isolated from the livers of mice infected with murine schistosomiasis, and substance P was extracted. Immunoreactive substance P was detected by RIA. The authenticity of the molecule was confirmed by elution profile on HPLC. Immunoreactive substance P, identified by immunostaining, localized to eosinophils derived from collagenase-dispersed granulomas. Granulomas were then probed for expression of the gene for substance P (preprotachykinin). Preprotachykinin mRNA was localized to granuloma eosinophils by in situ oligonucleotide hybridization. It is concluded that substance P is present within the granuloma as a result of preprotachykinin production by eosinophils.

The turnover of serotonin (5HT) was determined in the raphe area and cortex of mice infected with Pixuna, a strain of intermediate virulence of Venezuelan equine encephalomyelitis virus (VEEV). NMRI-mice, 24 days old, were inoculated intracerebrally (ic) with 300 LD50 of the virus. The animals were sacrificed 4, 7, 15, 21, 30, and 60 days postinoculation. 5HT and 5-hydroxyindoleacetic acid (5HIAA) in raphe and cortex were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Turnover rate of 5HT was determined by the administration of pargyline, p-chlorophenylalanine, and probenecid. The content of 5HT or 5HIAA and 5HT/5HIAA ratios were not significantly different in infected compared with control mice. However, a decrease of 5HT turnover rate, determined after pargyline treatment, was observed in the raphe and not in the cortex of infected mice at 4 and 7 days after the inoculation. The turnover rate/(5HT)0 in raphe is decreased in infected mice with signs of illness, suggesting a lower density of 5HT innervation in this brain area. The administration of p-chlorophenylalanine and probenecid showed that the cortex is also affected, but the synthesis is less modified than metabolism or elimination. Cell bodies of 5HT neurons seem to be more susceptible than projections to infection by Pixuna strain of VEEV.

Thermal inactivation of Venezuelan Equine Encephalomyelitis Virus (VEEV) was studied at temperatures from 26 degrees to 55 degrees C. Inactivation of infectivity took place by two thermodynamically different reactions, one of which predominated at temperatures below 44 degrees C and the other at higher temperatures. The presence of 1 or 2 M NaCl stabilized the VEE virus at low temperatures but enhanced the inactivation at high temperatures. This latter effect at temperatures higher than 50 degrees C, is associated with the occurrence of two-component survival curves. The different effects of hypertonic NaCl concentrations at the two ranges of temperature, are related to different mechanisms of inactivation operating at each range (protein denaturation and nucleic acid-RNA breakdown). Different kinetics of thermal inactivation at 55 degrees C were observed between virus strains with different virulence. However, no significant correlations was found between the virulence of the eleven VEE virus strains studied and their thermostability at 37 degres and 55 degrees C.

Nariva virus was first isolated in 1962 by Tikasingh et al. (1966) from Trinidadian rodents Zygodontomys b. brevicauda and was originally thought to be an arbovirus. It contains RNA, is ether-sensitive and haemadsorbs guinea-pig erythrocytes (Karbatsos, Buckley & Ardoin, 1969). Few of its properties are known, and since its structure and morphogenesis are also unknown, its taxonomic position is uncertain. We describe here observations on the structure and morphogenesis of Nariva virus propagated in BHK 21 cell cultures, thus providing some evidence for its classification. Monolayers of BHK 21 cells were grown in EM/TPB medium as described previously by (Macpherson & Stoker, 1962) and maintained in equal parts of EM/TPB and Basal medium Eagle (Eagle, 1955) with 3% foetal bovine serum, 0.05% of 2 m-tris and antibiotics; kanamycin and tylosin tartrate was additionally added. Nariva virus (prototype strain trvl-42520, 4th mouse brain passage) was obtained from Dr L. Spence (Trinidad Regional Virus Laboratory, Trinidad).

Fourteen strains of VEEV of diverse origin and antigenicity were classified into five virulence categories according to their efficiency of infection and nature of response in mice. Mice of ages up to 30 days represented distinct levels of responsiveness and were suitable for the differentiation of VEEV strains of highest to lowest virulence. Stepwise changes with age of the susceptibility or responsiveness of mice appeared to determined the type of response as predominantly lethal (D), dual or intermediate (DP) or protective (P).

Increasing utilization of arable land in southwestern Venezuela has led to a potential increase in human exposure to arbovirus infections. Since previous studies in the Catatumbo region of this area documented the presence of eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses, an attempt was made to study the transmission and maintenance of these viruses from 1973 to 1981. Isolations of EEE, VEE ID strains, Una, Itaqui , and Moju viruses were repeatedly obtained from mosquitoes, mostly Culex ( Melanoconion ) spp. and sentinel hamsters. The results indicate that these viruses constitute a potential hazard to public health in the area. Further, the strategic location of the Catatumbo region, between enzootic tropical foci of arboviruses, may provide circumstances and conditions for study of both enzootic maintenance and movement of these viruses.

Mice of different ages were infected i.p. or i.c. by 23 different strains of VEE virus. The course of the virus host interaction was specified in terms of the efficiency of infection, the outcome of infection as lethality or protection and the survival time. These separately quantifiable features all showed several host-maturation events that combine to provide a multifactorial specification of virus-strains and host-responses. This base-line for correlations with the responses of principal hosts (equidae and man) may be expanded to test correlations with the antigenic or in vitro characteristics of virus-strains.

Comparative analysis of structural virion polypeptides of 24 selected EEE virus strains, representing North and South American types, was performed by one-dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis (PAGE). The structural proteins of different EEE virus isolates, resolved by this method, exhibited mol.wts. values in the range of 57-60 X 10(3) for (E-1), 51-54 X 10(3) for (E-2) and 35-38 X 10(3) daltons for the core (NP) nucleocapsid. The exception was the South American human lethal virus, TRVL-89287 strain, which was shown to possess only a single envelope glycoprotein. The high molecular weight envelope (E-1) glycoprotein species was absent or co-migrated adjacent to the smaller envelope (E-2) glycoprotein. Results indicated similarities in the core (NP) proteins, however greater variability in the envelope (E-/ and/or E-2) glycoproteins. Based on these variations seven distinct profiles could be observed among the EEE virus strain studied. The classification based on the patterns of structural polypeptides obtained by SDS-PAGE of these strains does not correlate well with any other previously reported in vitro characteristics (antigenic subtypes, HTP elution profiles) nor with the in vivo virulence markers.