Association between Early Ischemic Changes and Collaterals in Acute Stroke: A Retrospective Study.

BACKGROUND AND PURPOSE: The quality of leptomeningeal collaterals may influence the speed of infarct progression in acute stroke. Our main objective was to evaluate the association of leptomeningeal collateral score and its interaction with time with ischemic changes on CT in patients with acute stroke. MATERIALS AND METHODS: Adult patients with acute stroke symptoms and anterior circulation large-vessel occlusion on CTA from 2015 to 2019 were included. Routinely performed NCCT and multiphase CTA were reviewed to assess ASPECTS and the leptomeningeal collateral score. We built multivariate regression models to assess the association between leptomeningeal collateral score and its interaction with time and ASPECTS. Performance measures to predict poor ASPECTS at different time thresholds (identified with receiver operating characteristic curve analysis) were estimated in a subgroup of patients with poor leptomeningeal collateral scores. RESULTS: Leptomeningeal collateral scores 0-1 were associated with lower ASPECTS, and the model with dichotomized and trichotomized leptomeningeal collateral score showed a significant multiplicative interaction between time and the leptomeningeal collateral score. The negative predictive value for poor ASPECTS was >0.9 for at least the first 3 hours from stroke onset to imaging, and the positive predictive value was <0.5 for every time threshold tested in the subgroup of patients with leptomeningeal collateral scores 0-3. CONCLUSIONS: Poor (0-1) leptomeningeal collateral scores were associated with lower ASPECTS, and an increase in time has a multiplicative interaction with the leptomeningeal collateral score on ASPECTS.

A new model of the formation of Pennsylvanian iron carbonate concretions hosting exceptional soft-bodied fossils in Mazon Creek, Illinois.

Preservation of Pennsylvanian-aged (307 Ma) soft-bodied fossils from Mazon Creek, Illinois, USA, is attributed to the formation of siderite concretions, which encapsulate the remains of terrestrial, freshwater, and marine flora and fauna. The narrow range of positive δ34 S values from pyrite in individual concretions suggests microenvironmentally limited ambient sulfate, which may have been rapidly exhausted by sulfate-reducing bacteria. Tissue of the decaying carcass was rapidly encased by early diagenetic pyrite and siderite produced within the sulfate reduction and methanogenic zones of the sediment, with continuation of the latter resulting in concretion cementation. Cross-sectional isotopic analyses (δ13 C and δ18 O) and mineralogical characterization of the concretions point to initiation of preservation in high porosity proto-concretions during the early phases of microbially induced decay. The proto-concretion was cemented prior to compaction of the sediments by siderite as a result of methanogenic production of 13 C-rich bicarbonate-which varies both between Essex and Braidwood concretions and between fossiliferous and unfossiliferous concretions. This work provides the first detailed geochemical study of the Mazon Creek siderite concretions and identifies the range of conditions allowing for exceptional soft-tissue fossil formation as seen at Mazon Creek.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

Transcriptional response of Atlantic salmon (Salmo salar) after primary versus secondary exposure to infectious salmon anemia virus (ISAV).

Following an infection with a specific pathogen, the acquired immune system of many teleostean fish, including salmonids, is known to retain a specific memory of the infectious agent, which protects the host against subsequent infections. For example, Atlantic salmon (Salmo salar) that have survived an infection with a low-virulence infectious salmon anemia virus (ISAV) isolate are less susceptible to subsequent ISAV infections. A greater understanding of the mechanisms and immunological components involved in this acquired protection against ISAV is fundamental for the development of efficacious vaccines and treatments against this pathogen. To better understand the immunity components involved in this observed resistance, we have used an Atlantic salmon DNA microarray to study the global gene expression responses of preexposed Atlantic salmon (fish having survived an infection with a low-virulence ISAV isolate) during the course of a secondary infection, 18 months later, with a high-virulence ISAV isolate. We present global gene expression patterns in both preexposed and naïve fish, following exposure by either cohabitation with infected fish or by direct intra-peritoneal injection of a high-virulence ISAV isolate. Our results show a clear reduction of ISAV viral loads in head-kidney of secondary infected fish compared to primary infected fish. Further, we note a lower-expression of many antiviral innate immunity genes in the secondary infected fish, such as the interferon induced GTP-binding protein Mx, CC-chemokine 19 and signal transducer and activator of transcription 1 (STAT 1), as well as MHC class I antigen presentation involved genes. Potential acquired immunity genes such as GILT, leukocyte antigen transcript CD37 and Ig mu chain C region membrane-bound form were observed to be over-expressed in secondary infected fish. The observed differential gene expression profile in secondary and primary infected fish head-kidney provides great insight into immunity components involved during primary and secondary ISAV infection.

Rangeomorphs, Thectardis (Porifera?) and dissolved organic carbon in the Ediacaran oceans.

The mid-Ediacaran Mistaken Point biota of Newfoundland represents the first morphologically complex organisms in the fossil record. At the classic Mistaken Point localities the biota is dominated by the enigmatic group of "fractally" branching organisms called rangeomorphs. One of the few exceptions to the rangeomorph body plan is the fossil Thectardis avalonensis, which has been reconstructed as an upright, open cone with its apex in the sediment. No biological affinity has been suggested for this fossil, but here we show that its body plan is consistent with the hydrodynamics of the sponge water-canal system. Further, given the habitat of Thectardis beneath the photic zone, and the apparent absence of an archenteron, movement, or a fractally designed body plan, we suggest that it is a sponge. The recognition of sponges in the Mistaken Point biota provides some of the earliest body fossil evidence for this group, which must have ranged through the Ediacaran based on biomarkers, molecular clocks, and their position on the metazoan tree of life, in spite of their sparse macroscopic fossil record. Should our interpretation be correct, it would imply that the paleoecology of the Mistaken Point biota was dominated by sponges and rangeomorphs, organisms that are either known or hypothesized to feed in large part on dissolved organic carbon (DOC). The biology of these two clades gives insight into the structure of the Ediacaran ocean, and indicates that a non-uniformitarian mechanism delivered labile DOC to the Mistaken Point seafloor.

Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats.

Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model.

Genetic markers of the immune response of Atlantic salmon (Salmo salar) to infectious salmon anemia virus (ISAV).

Infectious diseases among fish present an important economic burden for the aquaculture and fisheries industries around the world. For example, the infectious salmon anemia virus (ISAV) infects farmed Atlantic salmon (Salmo salar), and results in millions of dollars of lost revenue to salmon farmers. Although improved management and husbandry practices over the last few years have minimized the losses and the number of outbreaks, the risk of new virulent strains emerging is a looming threat to the viability and sustainability of this industry. A greater understanding of the host-pathogen interactions at the molecular level during the course of an infection thus remains of strategic importance for the development of molecular tools and efficient vaccines capable of minimizing losses in the eventual case of a new outbreak. Using a 32 k cDNA microarray platform (cGRASP), we have identified various signaling pathways and immune regulated genes, which are activated or repressed in Atlantic salmon head-kidney during the course of an ISAV infection. Gene expressions were measured at five different time-points: 6 h, 24 h, 3 d, 7 d and 16 d post-injection. The earliest time points showed only a few differentially expressed genes in ISAV injected fish, relative to sham injected controls, although as time progressed, many additional genes involved in key defense pathways were up-regulated including MHC type I, beta-2 microglobulin, TRIM 25 and CC chemokine 19. During the latest stage of the infection process, many genes related to oxygen transportation were under-expressed, which correlates well with the observed anemia that occurs prior to death in Atlantic salmon infected with virulent strains of ISAV.

Primary lymphoepithelioma-like carcinoma of the lung.

Primary lymphoepithelioma-like carcinoma (LELC) of the lung is a neoplasm seen most commonly in the nasopharynx of individuals from south China and Taiwan, and is strongly associated with the Epstein-Barr virus. The case of a 62-year-old Chinese man with a rare primary lung T2N1M0 LELC of the left lower lobe is presented. The lesion was further notable because of the presence of necrotizing granulomatous inflammation. The patient was treated with surgical resection. After it was determined that the neoplasm was of primary lung origin, adjunctive chemotherapy was initiated. The role of adjunctive chemotherapy in this setting is discussed.

Effect of autonomic neurotransmitters on excitable gap composition in canine atrial flutter.

Atrial arrhythmias are believed to be influenced by autonomic nervous system tone. We evaluated the effects of sympathetic and parasympathetic activation on atrial flutter (AF1) by determining the effects of norepinephrine (NE) and acetylcholine (ACh) on the composition of the excitable gap. A model of reentry around the tricuspid valve was produced in 17 chloralose anesthetized dogs using a Y-shaped lesion in the intercaval area that extended to the right atrial appendage. Excitable gap characteristics were determined during AF1 by scanning diastole with a single premature extrastimulus at progressively shorter coupling intervals to define the reset-response curve. Measurements were made during a constant infusion of NE (15 microg/min) into the right coronary artery and repeated during ACh infusion (2 microg/min) following a 15 min recovery period. The excitable gap (27 +/- 1 ms) was significantly (P < 0.001) increased by NE (34 +/- 1 ms) and ACh (50 +/- 2 ms). The fully excitable portion (7 +/- 1 ms) was also significantly (P < 0.001) increased by NE (17 +/- 1 ms) and ACh (43 +/- 2 ms). We conclude that both neurotransmitters increase the safety margin of full excitability ahead of the wavefront, demonstrating that parasympathetic and sympathetic activation can facilitate the persistence of this refractory atrial arrhythmia.

G(s) and adenylyl cyclase in transverse tubules of heart: implications for cAMP-dependent signaling.

The transverse tubules are highly specialized invaginations of the cardiac sarcolemmal membrane involved in excitation-contraction (EC) coupling. Several proteins directly involved in EC coupling have been shown to reside either in the transverse tubular membrane or in closely associated structures. With the use of immunofluorescence microscopy, we have found that G(S) and adenylyl cyclase, key elements in the beta-adrenergic signal transduction cascade, are essentially homogeneously distributed throughout the transverse tubular network of isolated rat ventricular myocytes. G(S), in particular, was much more abundant within the transverse tubular membrane than in the peripheral sarcolemma. Furthermore, both proteins are also present in the intercalated disk region. The location of these elements of the cAMP-signaling cascade within a few micrometers of every inotropic target suggests that control and action of this second messenger are quite local. Furthermore, a similar distribution is likely for negatively inotropic receptor systems that oppose G(S)-linked receptors at the level of adenylyl cyclase. Thus, in addition to their role in EC coupling, transverse tubules appear to be the primary site for signaling by inotropic agents.

Do beta 2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes?

We examined the role of beta 2-adrenergic receptors (ARs) in modulating calcium homeostasis in rat ventricular myocytes. Zinterol (10 microM), an agonist with a 25-fold greater affinity for beta 2-ARs over beta 1-ARs, modestly enhanced L-type calcium current (ICa) magnitude by approximately 30% and modestly accelerated the rate of Ca2+ concentration ([Ca2+]) decline (approximately 35%) but had little effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase). However, 1 microM of the highly selective beta 1-AR antagonist CGP-20712A completely blocked the ICa increase induced by 10 microM zinterol. Pretreatment of cells with pertussis toxin (PTX) did not alter ICa enhancement by 10 microM zinterol, although it did abolish the ability of acetylcholine to block the forskolin-induced enhancement of ICa. Zinterol (10 microM) approximately doubled adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, although one-half of this increase was blocked by CGP-20712A. In contrast, 1 microM of the nonselective beta-agonist isoproterenol increased cAMP production 15-fold. Thus we found no evidence that activation of beta 2-ARs modulates calcium homeostasis in rat ventricular myocytes, even after treatment with PTX.

Current uses of virtual reality for children with disabilities.

Technological advances, including the use of virtual reality, have contributed enormously to improving the treatment, training, and quality of life of children with disabilities. This paper describes the advantages of VR for children with disabilities, how VR can minimize the effects of a disability, the role of VR in training and skills enhancement, and how social participation and the child's quality of life may be improved through the use of VR. Examples from published literature and Internet sites are given of current and completed projects which focus on improving the lives of children with disabilities. The research describing the efficacy of knowledge and skills transfer from a virtual environment to the real world are examined in relation to children with disabilities. Finally, the current limitations and future directions of VR for children with disabilities are considered.

Effects of procainamide on the excitable gap composition in a canine model of atrial flutter.

The effects of increasing concentrations of procainamide on the composition of the excitable gap were determined in a canine model of atrial flutter. Using the model of a Y-shaped lesion in the right atrium, reentry around the tricuspid valve was induced by burst pacing in 10 open-chest chloralose-anesthetized dogs. Diastole was scanned with a single premature stimulus and the relationship between the coupling interval of the premature beat and the return cycle length (CL) determined a reset-response curve that described the excitable gap. This was repeated up to the maximum flutter CL while infusing procainamide (30 mg/kg) over 1 h. Procainamide progressively prolonged the flutter CL from 131 +/- 21 (+/-SD) to 188 +/- 46 ms (p < 0.01) and the effective refractory period from 96 +/- 19 to 149 +/- 47 ms (p < 0.01). At peak plasma levels of 77 +/- 33 mumol/L the drug terminated flutter only in two dogs. Neither the duration (35 +/- 10 to 39 +/- 13 ms) nor the composition of the excitable gap changed on drug. A fully excitable portion (7 +/- 3 ms or 20 +/- 11% of the excitable gap) persisted on procainamide (7 +/- 3 ms or 19 +/- 9% of the excitable gap). It was concluded that procainamide prolongs the atrial flutter CL and the effective refractory period but does not change either the duration or composition of the excitable gap even at plasma concentrations that significantly exceed those recommended in man.

Cyclic ADP-ribose does not regulate sarcoplasmic reticulum Ca2+ release in intact cardiac myocytes.

Cyclic ADP-ribose (cADPR), an intracellular second messenger known to mobilize Ca2+ in sea urchin eggs, has been implicated in modulating Ca2+ release in a variety of mammalian tissues. On the basis of studies of isolated cardiac sarcoplasmic reticulum (SR) vesicles and single SR Ca2+ release channels, cADPR has also been proposed to be a modulator of SR Ca2+ release in heart. In the present study, we directly examined the ability of cADPR to trigger SR Ca2+ release and to modulate Ca(2+)-induced Ca2+ release (CICR) in intact rat ventricular myocytes. Voltage-clamped myocytes were dialyzed with up to 100 mumol/L caged cADPR and 0.6 mumol/L calmodulin along with the Ca(2+)-sensitive dye fluo 3. A step increase in the cADPR concentration induced by flash photolysis of caged cADPR neither directly triggered SR Ca2+ release nor modulated CICR in intact myocytes. In contrast, under similar conditions, extracellular application of caffeine (1 to 2.5 mmol/L) onto myocytes produced both effects. Under equivalent conditions, flash photolysis of caged cADPR-loaded sea urchin eggs resulted in large Ca2+ transients. Further, the sustained presence of high cytosolic concentrations of either cADPR or its antagonist, 8-amino-cADPR, was ineffective in altering normal CICR in myocytes. These findings indicate that cADPR does not regulate SR Ca2+ release in intact cardiac myocytes.

Ca2+-induced current oscillations in rabbit ventricular myocytes.

Transient currents are activated by spontaneous Ca2+ oscillations in rabbit ventricular myocytes. We investigated the ionic basis for these transient currents under conditions in which K+ currents would be expected to be blocked. Holding cells under voltage clamp at positive potentials leads to a rise in intracellular Ca2+ via reversal of the Na+-Ca2+ exchanger and subsequently to the initiation of spontaneous Ca2+ transients, presumably from a Ca2+-overloaded sarcoplasmic reticulum. The current transients associated with these Ca2+ transients reversed at about +10 to +15 mV under conditions of approximately symmetrical Cl-. In the absence of Cl-, this current was inward at all potentials examined over the range from -88 to +72 mV, consistent with a Na+-Ca2+ exchanger current. In the absence of Na+, the repetitive spontaneous Ca2+ transients could be initiated by a brief train of depolarizations to activate the inward Ca2+ current. Under such conditions, the current was found to reverse at -3 mV when the equilibrium potential of Cl- (ECl) was -2 mV, and the reversal potential shifted to -32 mV when internal Cl- was lowered, to make ECl -33 mV. Thus, in the absence of Na+, it appears that the current is exclusively a Ca2+-activated Cl- current. There is no evidence to indicate the presence of a Ca2+-activated cationic conductance. Further, our results demonstrate that the Ca2+-activated Cl- conductance can carry inward current at potentials more negative to ECl in rabbit ventricular myocytes and is therefore likely to contribute to the arrhythmogenic delayed afterdepolarizations that occur in Ca2+-overloaded cells.

A prospective comparison of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in cataract and intraocular lens implant surgery.

We performed a prospective randomized clinical trial of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in routine extracapsular cataract extraction with posterior chamber lens implantation or in secondary anterior chamber lens implantation. Seventy consecutive patients were enrolled. The viscoelastic agents were compared in four areas intraoperatively: ease of injection, ease of removal, clarity of field and ability to hold back ocular tissues. Healon was significantly superior to Orcolon in all four areas. Further evaluations were performed on the first day and at 2 weeks postoperatively. Measurements of intraocular pressure (IOP) by Goldmann applanation and evaluations of corneal edema, epithelial keratitis and anterior chamber cellular reaction were recorded. Multivariable statistical analysis revealed only one difference between the two groups: significantly more patients in the Orcolon group (eight cases) than in the Healon group (two cases) had an IOP of 21 mm Hg or greater on the first postoperative day.

Fibrous histiocytoma of the corneoscleral limbus and conjunctiva.

An 11-year-old boy and a 28-year-old woman each had a painless, slowly enlarging, elevated, yellow lesion of the inferior corneoscleral limbus and adjacent cornea and conjunctiva of the left eye. Histopathologic examination of both lesions disclosed involvement of the conjunctival substantia propria and the adjacent limbal and peripheral corneal stroma by a nonencapsulated, dense infiltrate composed of elongated fibrocytic cells, plump histiocytic cells occasionally with a vacuolated cytoplasm, some multinucleated giant cells, and scattered lymphocytes. The diagnosis in each case was fibrous histiocytoma. Both patients were otherwise in good health with no dermatologic, systemic, or other ocular abnormalities.