Acute Nonhemorrhagic Adrenal Infarction in Pregnancy: 10-Year MRI Incidence and Patient Outcomes at a Single Institution.

OBJECTIVE: The purpose of this study was to retrospectively investigate the MRI incidence of nonhemorrhagic adrenal infarction in pregnant women undergoing MRI evaluation of acute abdominal or flank pain, assess the MRI features quantitatively, and report patient outcomes. MATERIALS AND METHODS: All abdominal MRI examinations of pregnant women with acute pain at one institution from May 2005 to April 2015 were reviewed. The adrenals were evaluated for abnormal morphologic and signal intensity characteristics described in the literature characterizing nonhemorrhagic adrenal infarction and were compared with the contralateral adrenal by paired t tests. The findings were correlated with clinical presentation. Patient demographics and outcomes were gathered from the medical record. RESULTS: Findings of nonhemorrhagic adrenal infarction were present in 5 of 379 (1.3%) examinations of four pregnant patients (mean age, 28 years; range, 20.8-33.9 years; mean gestational age, 26 weeks; range, 16-35 weeks). MRI features included lengthening (mean, 39.8 versus 21.2 mm) (p = 0.005) and increased T2 signal intensity (p = 0.001) of the infarcted adrenal with surrounding edema and without T1 signal intensity suggesting hemorrhage. No alternative diagnosis was identified. All patients presented with severe acute abdominal or flank pain on the same side as the MRI findings, tenderness to palpation, and mild leukocytosis. All women delivered healthy infants. CONCLUSION: Unilateral nonhemorrhagic adrenal infarction was identified in 1.3% of abdominal MRI examinations performed for pregnant women with acute abdominal or flank pain. Knowledge of the MRI characteristics of this entity is important for recognizing it and may prevent further potentially invasive tests, procedures, or missed diagnoses.

Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop.

Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane-penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody-based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo-EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to the static surface-exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody-based neutralization of PA and bring into focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines.

Near-equilibrium isotope fractionation during planetesimal evaporation.

Silicon and Mg in differentiated rocky bodies exhibit heavy isotope enrichments that have been attributed to evaporation of partially or entirely molten planetesimals. We evaluate the mechanisms of planetesimal evaporation in the early solar system and the conditions that controled attendant isotope fractionations. Energy balance at the surface of a body accreted within ~1 Myr of CAI formation and heated from within by 26Al decay results in internal temperatures exceeding the silicate solidus, producing a transient magma ocean with a thin surface boundary layer of order < 1 meter that would be subject to foundering. Bodies that are massive enough to form magma oceans by radioisotope decay (≥ 0.1% M ⊕) can retain hot rock vapor even in the absence of ambient nebular gas. We find that a steady-state rock vapor forms within minutes to hours and results from a balance between rates of magma evaporation and atmospheric escape. Vapor pressure buildup adjacent to the surfaces of the evaporating magmas would have inevitably led to an approach to equilibrium isotope partitioning between the vapor phase and the silicate melt. Numerical simulations of this near-equilibrium evaporation process for a body with a radius of ~ 700 km yield a steady-state far-field vapor pressure of 10-8 bar and a vapor pressure at the surface of 10-4 bar, corresponding to 95% saturation. Approaches to equilibrium isotope fractionation between vapor and melt should have been the norm during planet formation due to the formation of steady-state rock vapor atmospheres and/or the presence of protostellar gas. We model the Si and Mg isotopic composition of bulk Earth as a consequence of accretion of planetesimals that evaporated subject to the conditions described above. The results show that the best fit to bulk Earth is for a carbonaceous chondrite-like source material with about 12% loss of Mg and 15% loss of Si resulting from near-equilibrium evaporation into the solar protostellar disk of H2 on timescales of 104 to 105 years.

Dual energy CT for evaluation of polycystic kidneys: a multi reader study of interpretation time and diagnostic confidence.

PURPOSE: To compare dual-energy CT (DECT) iodine overlay images with renal mass protocol CT in the evaluation of polycystic kidneys with respect to reading time, diagnostic confidence, and detection of renal lesions that are not definitively benign. METHODS: Following IRB approval, portal venous phase dual-source DECT scans performed between September 2013 and February 2016 from 55 patients (mean age 67 ± 15 years, 31 male, 24 female) with polycystic kidneys (4 or more cysts) were included. For each patient, two image sets were created: (1) DECT post-processed iodine overlay images and (2) simulated renal mass protocol CT images (virtual noncontrast and mixed images). Two radiologists independently retrospectively reviewed both sets at separate time points, evaluating for the presence of lesions that were not definitively benign (enhancing lesions or Bosniak IIF cysts), as well as reading times and Likert scale diagnostic confidence ratings (scaled 1-5) for the presence of non-benign lesions. Reading times were compared with a t test, diagnostic confidence with a McNemar test, and lesion number detection with Cohen's kappa test. RESULTS: Iodine overlay images were read faster (mean 55 ± 26 s) than renal mass protocol (mean 105 ± 51 s) (p < 0.001). Readers assigned the highest diagnostic confidence rating in 64% using iodine overlay series, compared to 17% using renal mass protocol (p < 0.0001). The proportion of patients with recorded lesions was not significantly different between methods (p = 0.62). CONCLUSIONS: DECT improves lesion assessment in polycystic kidneys by decreasing reading times and increasing diagnostic confidence, without affecting lesion detection rates.

Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells.

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles-secretome-that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.

Pressure-dependent isotopic composition of iron alloys.

Our current understanding of Earth's core formation is limited by the fact that this profound event is far removed from us physically and temporally. The composition of the iron metal in the core was a result of the conditions of its formation, which has important implications for our planet's geochemical evolution and physical history. We present experimental and theoretical evidence for the effect of pressure on iron isotopic composition, which we found to vary according to the alloy tested (FeO, FeH(x), or Fe3C versus pure Fe). These results suggest that hydrogen or carbon is not the major light-element component in the core. The pressure dependence of iron isotopic composition provides an independent constraint on Earth's core composition.

Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: clinical and angiographic study.

OBJECTIVES: This study was undertaken to test the hypothesis that early inversion of T waves after thrombolytic therapy for acute myocardial infarction predicts patency of the infarct-related artery with high Thrombolysis in Myocardial Infarction (TIMI) perfusion flow and better in-hospital outcome. BACKGROUND: Although numerous studies have demonstrated a strong association between early resolution of ST segment elevation after acute myocardial infarction and successful thrombolysis, little is known about early changes in T waves after thrombolytic therapy. METHODS: Ninety-four consecutive patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) were studied with admission and predischarge radionuclide ventriculography and with coronary angiography within 72 h of admission. Patient stratification was based on the presence or absence of early (within 24 h) T wave inversion. RESULTS: Early T wave inversion was associated with a higher patency rate of the infarct-related artery (90% vs. 65%, p < 0.02) and less severe residual stenosis ([mean +/- SD] 73 +/- 27 vs. 83 +/- 22, p = 0.06), and when only TIMI perfusion grade 3 was considered, the difference was even greater (77% vs. 41%, p < 0.001). Patients with early inversion of T waves had a lower peak creatine kinase value ([mean +/- SD] 678 +/- 480 vs. 1,076 +/- 620, p < 0.01), and although a similar percent of patients with and without early T wave inversion had a normal ejection fraction (> or = 55%) on admission, a higher percent of patients with early inversion had a normal ejection fraction at hospital discharge (71% vs. 44%, p < 0.03). Early T wave inversion anticipated a more benign in-hospital clinical course with a lower incidence of adverse cardiac events (10% vs. 33%, p < 0.02). CONCLUSIONS: Early inversion of T waves in patients with acute myocardial infarction treated with thrombolytic therapy suggests patency of the infarct-related artery, better perfusion grade and left ventricular function and a more benign in-hospital course.

Audiological evaluation of nonalcoholic, drug-free posttraumatic stress disorder patients.

Auditory functions of 32 Israeli soldiers with posttraumatic stress disorder (PTSD) were evaluated and compared with those of 32 matched controls without PTSD. The evaluation included peripheral auditory functions, tolerance to noise, and central auditory informational functions. Tolerance of intense auditory stimuli by PTSD patients was similar to that of controls. Significant differences were found between left and right ear central auditory functions in a subgroup of 13 PTSD subjects, but neither in other PTSD patients nor in controls. These findings are discussed in the light of previous research concerning abnormal responses to auditory stimulus in PTSD, hemispheric disconnection, alexithymia, and psychosomatic disorders.

High-affinity imipramine binding and serotonin uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients.

The authors evaluated high-affinity [3H]imipramine binding and [3H]serotonin uptake to platelets in eight adolescent and 10 adult patients who met DSM-III criteria for obsessive-compulsive disorder in comparison with those of normal control subjects of similar ages. The maximal binding of [3H]imipramine was significantly lower in adults and adolescents with obsessive-compulsive disorder than in the control subjects. No differences between groups in the affinity of [3H]imipramine to its binding sites or in serotonin uptake kinetic measures were detected. The lower density of [3H]imipramine binding sites in platelet membrane in patients with obsessive-compulsive disorder might implicate involvement of the serotonergic system or might represent an adaptive response to a chronic disease.

Factors influencing mossy fiber collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus.

Collateral sprouting of dentate granule cell axons, the mossy fibers, occurs in response to denervation, kindling, or excitotoxic damage to the hippocampus. Organotypic slice culture of rodent hippocampal tissue is a model system for the controlled study of collateral sprouting in vitro. Organotypic roller-tube cultures were prepared from hippocampal slices derived from postnatal day 7 mice. The Timm heavy metal stain and densitometry were used to assay the degree of mossy fiber collateral sprouting in the molecular layer of the hippocampal dentate gyrus. Factors influencing mossy fiber collateral sprouting were time in culture, positional origin of the slice culture along the septotemporal axis of the hippocampus, and presence of attached subicular-entorhinal cortical tissues. Collateral sprouting in the molecular layer was first detected after 6 days in culture and increased steadily thereafter. By 2 weeks considerable sprouting was apparent, and at 3 weeks intense sprouting was observed within the molecular layer. An intrinsic septal-to-temporal gradient of collateral sprouting was apparent at 14 days in culture. To determine whether differential damage to the mossy fibers was the basis for the differences in collateral sprouting along the septotemporal axis, we made complete transections of the mossy fiber projection as it exited the dentate hilus at various levels along the septotemporal axis; no differences were found on subsequent collateral sprouting in the dentate molecular layer. Timm-stained hippocampal cultures with an attached entorhinal cortex, a major source of afferent innervation to the dentate granule cells, displayed significantly less collateral sprouting at 10 days in culture compared to that in cultures from adjacent sections without attached subicular-entorhinal tissues present. Thus, time in culture, position along the septotemporal axis, and presence of afferent cortical tissues influence aberrant neurite collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus.

Solid-phase immune electron microscopy (SPIEM) for rapid viral diagnosis.

Immune electron microscopy (IEM) is one of the fastest and most sensitive methods for the detection and diagnosis of viruses. This technique is based on formation of immune complexes of the virus with its corresponding antibody. In IEM optimal precipitation depends on a correct ratio, and there is a prozone effect. These problems can be overcome by using the solid-phase immune electron microscopic (SPIEM) technique. In this technique the antibody is attached to a particle which is used for 'fishing' the virus to be examined out of the suspension. After low speed centrifugation the preparation is treated either for observation in the transmission electron microscope or in the scanning electron microscope. In 'positive' samples the virus is seen attached to the surface of the particle. We report here results with S. aureus as the solid phase for the detection of Sindbis virus. The anti-Sindbis gamma globulins are attached to the bacteria by means of protein A present on their surface.

Molecular epidemiology of hematological neoplasms--present status and future directions.

The field of molecular epidemiology, using modern epidemiological approaches and taking the advantage of the advances in molecular biology can provide new tools for the exploration of etiological determinants, either environmental or hereditary, in the development of hematological neoplasms. It is now possible to identify some host susceptibility characteristics, to measure the effective dose of exposure, and to identify early, pre-clinical biological effects, using sensitive and specific biomarkers. The significant variation in the incidence of hematological neoplasms in different geographical areas, races, and age groups, the high rates of familial aggregation in certain populations, the involvement of protooncogenes and tumor suppressor genes in the development of hematological neoplasms, as well as of many environmental agents such as chemicals, radiation, and viruses, support the important role of molecular epidemiology in the investigation of the development of hematological neoplasms.

The next stage: molecular epidemiology.

The traditional approach in epidemiology of relating exposure to an environmental agent such as a drug or infective agent has been to measure an overall risk (i.e., average and then "adjust risk for demographic variables and other confounders"). An attempt is sometimes made to define a "susceptible" subgroup. The analyses are usually based on good statistical methodology rather than an understanding of the interaction of body of host and agent. A twofold risk for 1000 exposed versus nonexposed people could be an average twofold risk for all 1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host interaction). Clearly, finding the 100 individuals with a 20-fold risk has much greater clinical importance than a twofold risk for 1000 people. The world of epidemiology may be changing-we may soon be able to define risk based on genetic susceptibility, at least sometimes.

A simplified microwell pseudoreplica for the detection of viruses by electron microscopy and immunoelectron microscopy.

Simplified procedures for immunoelectron microscopy (IEM) and electron microscopy (EM) are described. The procedures employ the principle of agar filtration and pseudoreplication. The modification consisted of the use of microwells for storage of gels with or without antiserum (for IEM or EM, respectively) and an array of containers in which pseudoreplication and negative staining were performed. The containers were prepared from 5 ml syringes from which the needle holding parts were cut. This device enabled simultaneous and rapid handling of specimens. With Sindbis virus as a model, our microwell pseudoreplica IEM (MW-PR-IEM) was compared to six other IEM techniques and was found to be the most rapid and sensitive technique. With the MW-PR-IEM technique, the specific minimal detection limit (detection of clumps) was 1.5 x 10(7) virus particles per ml, and the non-specific detection limit (detection of single virions) was 1.8 x 10(6) virus particles per ml.

Cholinotoxicity of the ethylcholine aziridinium ion in primary cultures from rat central nervous system.

The cytotoxic effects of ethylcholine aziridinium ion (AF64A) were studied in primary cultures prepared from either whole brain, septum, or midbrain of fetal rats. AF64A, at concentrations up to 22.5 microM, significantly reduced the number of acetylcholinesterase-stained cells without affecting the number of dopaminergic neurons or their ability to take up and release [3H]dopamine. Many of the survived acetylcholinesterase-stained cells appeared with intact somata but damaged processes, indicating a retrograde degeneration starting at the nerve terminal. Higher concentrations of AF64A (greater than 22.5 microM), caused general toxicity which was expressed by degeneration of various neuronal and glial cells. Choline (500 microM), significantly protected the cells from AF64A induced cytotoxicity. The results are consistent with a previously described kinetic model, that predicted a dual action of AF64A: selective cholinotoxicity at low concentrations and non-selective cytotoxicity at higher concentrations.

Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization-embryo transfer than patients with tubal infertility.

OBJECTIVE: To evaluate the outcome of IVF in patients with stages III and IV endometriosis. DESIGN: Retrospective study. SETTING: The Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel. PATIENT(S): Fifty-eight patients with stages III and IV endometriosis and 60 patients with tubal infertility. INTERVENTION(S): IVF-ET for all couples. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and birth rates. RESULT(S): The comparison between patients with endometriosis and those with tubal infertility indicated that the former had a poor IVF outcome in terms of reduced fertilization rate (40% vs. 70%), reduced pregnancy rate per cycle (10.6% vs. 22.4%), and reduced birth rate per cycle (6.7% vs. 16.6%). The differences were statistically significant. CONCLUSION(S): The results show an unfavorable outcome of IVF-ET in patients with endometriosis when compared with those who have tubal infertility.

Selective adherence of neurons and glial cells from dissociated cerebral and spinal cord microcarrier cultures.

In stationary cultures of dissociated brain and spinal cord grown on microcarriers (MCs), the neuronal and ependymal cells attached to the MCs forming floating aggregates in which they grow in a three-dimensional pattern. The glial and meningeal elements on the contrary, tend to dissociate from the aggregates and adhere to the plastic dish where they divide to form a monolayer. This different behavior of CNS components is not observed in rotating cultures in which all CNS cells remain attached to the MCs and develop into mature floating structures. This cell separation in stationary MC-cultures which is documented here by SEM and immunocytochemistry, may be useful for analysis and evaluation of the metabolic biochemical events of each of the cellular components derived from the same culture.

Irradiation neurotoxicity assessed in organotypic cultures of rat hippocampus.

The neurotoxic effects of irradiation on the developing nervous system were studied in organotypic cultures of hippocampus prepared from newborn Sprague-Dawley rats. Hippocampus slices of 7-day-old rats were irradiated at the day of explantation at doses of 1, 2 and 4 Gy, and cultured in a roller drum for a fortnight. Light and electron microscopy showed remarkable damage to neuronal cells following irradiation, oligodendrocytes and myelogenesis being also affected. In contrast to alterations in neuronal perikarya, no morphological changes in synapses were obvious, though their number seemed to be reduced after irradiation with 4 Gy. These results confirm that low dose radiation produces damage to the central nervous system not only pre-natally, but even in post-natal periods of differentiation and development.

Neuronal cell cultures as a model for assessing neurotoxicity induced by encephalitic viruses.

Primary dispersed and organotypic cultures were prepared from selected brain areas and spinal cords of rat (Sprague-Dawley) and mouse (SJL/OLA(F) Ness-Ziona) fetuses and neonates. Following fiber regeneration, synapse formation and myelination, cultures were infected with one of the following viruses: Rabies CVS-21 strain, Sindbis Alphavirus, West-Nile Flavivirus and Theiler Murine Encephalomyelitis virus. Light and electron microscopical studies showed clear differences in the target cells for virus infection; time of viral replication and in the intensity and specificity of the cytopathic effects induced by these viruses. Thus, Sindbis and Theiler viruses induced severe cytotoxicity and demyelination due to rapid viral replication in both neurons and all glial cell types. Rabies and West-Nile viruses, on the other hand, replicated mainly in neurons and at a much slower rate, causing only mild damage to the cells and the myelin sheath. A very specific alignment of West-Nile virions was observed along the interperiod lines of the myelin sheath in several myelinated axons. This peculiar arrangement of the virions, entrapped between the myelin lamellae may lead to a novel concept in the understanding of viral infection.

Selective neurotoxicity induced by the ionophore lasalocid in rat dissociated cerebral cultures, involvement of the NMDA receptor/channel.

An in vitro model of dissociated cerebral cultures, prepared from prenatal 15-16-days rat fetuses, was used to further characterize the neurotoxic effects caused by the antibiotic ionophore lasalocid-X-537A. The damage caused by lasalocid (1-2 microM, 2-4 hr) included swelling of perikarya, followed by cytolysis of most neurons present in the cultures. The neuronal damage was dose-dependent, noticeable at concentrations above 0.5 microM, and was more pronounced in established cultures (14 days in vitro-DIV) than in younger ones (7 DIV). Unlike neurons, no damage was observed in glia and other non-neuronal cells present in the cultures by exposure to 2 microM lasalocid. Moreover, the drug was not toxic for cultures of rat astrocytes and C6 glioma cells. Another calcium ionophore A-23187 (calcimycin, 1 microM), destroyed both neuronal and non-neuronal cells within 1 hr. Ca2+ influx was increased by 140% in cultures exposed to lasalocid (1.5 microM). The lasalocid neurotoxic effects were neither inhibited by 10 microM nimodipine (a calcium channel antagonist) nor by 10 microM 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)(a non-N-methyl-D-aspartic acid (NMDA) receptor antagonist), but were exclusively blocked by 10 microM MK-801 (a non-competitive NMDA receptor/channel antagonist). The neurotoxicity induced by lasalocid was further confirmed by measurements of lactate dehydrogenase (LDH) released into the media. Lasalocid (1.5 microM) induced the release of both LDH and arachidonic acid (AA) (by 8 and 4 fold of control values, respectively), and this was blocked by MK-801 but not by CNQX. These results are in according with the observations that activation of calcium influx through the NMDA receptor leads to activation of phospholipase A2 (PLA2) and release of AA. In contrast, MK-801 did not block the release of either LDH or AA mediated by the calcium ionophore A-23187 (1 microM) in these cultures. [3H]-MK-801 binding to washed rat cortical membranes, a measure of direct interaction with the NMDA receptor/channel complex, was not affected by lasalocid either alone or in the presence of glutamate and glycine. [3H]-D-aspartate release, a measure of excitatory amino acid (EAA) secretion mediated by NMDA receptor activation, was increased by lasalocid and could be blocked by MK-801. These observations suggest that lasalocid induces selective neurotoxicity, which involves the NMDA receptor/channel complex, possibly indirectly, resulted in elevated intracellular Ca2+ levels and the subsequent glutamate or aspartate release.