bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Evolutionary Intermediates in the Host Adaptation of Canine Parvovirus
Authors: Stucker Karla M. , Pagan Israel , Cifuente Javier O. , Kaelber Jason T. , Lillie Tyler D. , Hafenstein Susan , Holmes Edward C. , Parrish Colin R.
Published: November 2011

The adaptation of viruses to new hosts is a poorly understood process likely involving a variety of viral structures and functions that allow efficient replication and spread. Canine parvovirus (CPV) emerged in the late 1970s as a host-range variant of a virus related to feline panleukopenia virus (FPV). Within a few years of its emergence in dogs, there was a worldwide replacement of the initial virus strain (CPV type 2) by a variant (CPV type 2a) characterized by four amino acid differences in the capsid protein. However, the evolutionary processes that underlie the acquisition of these four mutations, as well as their effects on viral fitness, both singly and in combination, are still uncertain. Using a comprehensive experimental analysis of multiple intermediate mutational combinations, we show that these four capsid mutations act in concert to alter antigenicity, cell receptor binding, and relative
in vitro
growth in feline cells. Hence, host adaptation involved complex interactions among both surface-exposed and buried capsid mutations that together altered cell infection and immune escape properties of the viruses. Notably, most intermediate viral genotypes containing different combinations of the four key amino acids possessed markedly lower fitness than the wild-type viruses.
Conventional Protein Kinase C-α (PKC-α) and PKC-β Negatively Regulate RIG-I Antiviral Signal Transduction
Authors: Maharaj Natalya P. , Wies Effi , Stoll Andrej , Gack Michaela U.
Published: November 2011

Retinoic acid-inducible gene I (RIG-I) is a key sensor for viral RNA in the cytosol, and it initiates a signaling cascade that leads to the establishment of an interferon (IFN)-mediated antiviral state. Because of its integral role in immune signaling, RIG-I activity must be precisely controlled. Recent studies have shown that RIG-I CARD-dependent signaling function is regulated by the dynamic balance between phosphorylation and TRIM25-induced K
63
-linked ubiquitination. While ubiquitination of RIG-I is critical for RIG-I's ability to induce an antiviral IFN response, phosphorylation of RIG-I at S
8
or T
170
suppresses RIG-I signal-transducing activity under normal conditions. Here, we not only further define the roles of S
8
and T
170
phosphorylation for controlling RIG-I activity but also identify conventional protein kinase C-α (PKC-α) and PKC-β as important negative regulators of the RIG-I signaling pathway. Mutational analysis indicated that while the phosphorylation of S
8
or T
170
potently inhibits RIG-I downstream signaling, the dephosphorylation of RIG-I at both residues is necessary for optimal TRIM25 binding and ubiquitination-mediated RIG-I activation. Furthermore, exogenous expression, gene silencing, and specific inhibitor treatment demonstrated that PKC-α/β are the primary kinases responsible for RIG-I S
8
and T
170
phosphorylation. Coimmunoprecipitation showed that PKC-α/β interact with RIG-I under normal conditions, leading to its phosphorylation, which suppresses TRIM25 binding, RIG-I CARD ubiquitination, and thereby RIG-I-mediated IFN induction. PKC-α/β double-knockdown cells exhibited markedly decreased S
8
/T
170
phosphorylation levels of RIG-I and resistance to infection by vesicular stomatitis virus. Thus, these findings demonstrate that PKC-α/β-induced RIG-I phosphorylation is a critical regulatory mechanism for controlling RIG-I antiviral signal transduction under normal conditions.
Sports helmets now and in the future
Authors: McIntosh Andrew Stuart , Andersen Thor Einar , Bahr Roald , Greenwald Richard , Kleiven Svein , Turner Michael , Varese Massimo , McCrory Paul
Published: November 2011

The paper reports on a symposium on sports helmets and presents a synthesis of information and opinion from a range of presenters and disciplines. A review of the literature shows that helmets play an important role in head injury prevention and control. Helmets have been shown to be very efficacious and effective in a range of sports and in preventing specific head injury risks, especially moderate to severe head injury. The symposium emphasised the importance of helmet standards and the need for further development. There are calls for helmets that address the needs of competitive (elite) athletes separate to helmets for recreational athletes. Deficiencies in the evidence base for head injury risks and helmet efficacy and effectiveness were identified in some sports. Issues in designing helmets that are suitable to prevent severe head injuries and concussion were discussed and explained from biomechanical and engineering perspectives. The need to evaluate helmet performance in oblique impacts and incorporate this into standards was covered in a number of presentations. There are emerging opportunities with in-helmet technology to improve impact performance or to measure impact exposure. In-helmet technology as it matures may provide critical information on the severity of the impact, the location of the injured athlete, for example, snowboarder, and assist in the retrieval and immediate, as well as the long-term medical management of the athlete. It was identified that athletes, families and sports organisations can benefit from access to information on helmet performance. The importance of selecting the appropriate-sized helmet and ensuring that the helmet and visor were adjusted and restrained optimally was emphasised. The translation pathway from the science to new and better helmets is the development of appropriate helmet standards and the requirement for only helmets to be used that are certified to those standards.
Beyond the fireground: injuries in the fire service
Authors: Poplin Gerald S , Harris Robin B , Pollack Keshia M , Peate Wayne F , Burgess Jefferey L
Published: November 2011

Background

Although firefighting and emergency medical services are high-risk professions, few studies have identified the aetiology of injury in the fire service beyond the fireground.

Methods

Data were collected for work-related injuries in a medium-sized metropolitan fire department. In a descriptive study, the factors explored included the nature of injury, agent, mechanism, body location, environment, abbreviated injury scale (AIS), functional capacity index (FCI) and lost time status.

Results

From 2004 to 2009, the annual injury incidence rate averaged 17.7 per 100 employees. One-third of all injuries (32.9%) resulted from physical exercise activities, while patient transport, training drills and fireground operations resulted in 16.9%, 11.1% and 10.2% of injuries, respectively. For all job operations, sprains and strains were the most prevalent type of injury (40.2–85.2%), followed by contusions and lacerations (7.7–26.1%). The third most common injury was related to the conventional hazards of the individual job operation. Most injuries (n=862, 95.6%) were minor in severity, while 4.3% of injuries were classified as having some impedance of normal function (FCI 3). Moderate injuries (AIS 2) were infrequent, but comprised a greater proportion of fireground injuries (8.7%) than the other activities (1.0–4.1%); however, lost time injuries were more frequent for patient transport (46.1%) than other operations (22.0–29.1%).

Conclusions

Physical exercise, patient transport and training activities were responsible for a greater percentage of injuries than fireground operations. Focused efforts to improve the characterisation of risks during these more diverse set of work processes should help guide the development of salient strategies for injury prevention.
Current endovascular treatment options of dural venous sinus thrombosis: a review of the literature
Authors: Gala Nihar B , Agarwal Nitin , Barrese James , Gandhi Chirag D , Prestigiacomo Charles Joseph
Published: November 2011

Dural venous sinus thrombosis, although relatively rare, has the propensity to cause potentially fatal conditions, such as stroke. This review presents the current endovascular treatment and management options for dural venous sinus thrombosis and provides current recommendations. Select databases were utilized for an exhaustive literature search with key search terms in efforts to obtain all relevant cases to endovascular treatment of dural venous sinus thrombosis. Recommendations for management options include initially the use of anticoagulation. For patients with a poor prognosis, local thrombolysis with urokinase or recombinant tissue plasminogen activator should be initiated. Ultimately, if the patient is not a good candidate for local or systemic thrombolysis, treatment via rheolytic thrombectomy should be employed.
Reporting standards for angiographic evaluation and endovascular treatment of cerebral arteriovenous malformations: Table 1
Authors: Jayaraman Mahesh V , Meyers Philip M , Derdeyn Colin P , Fraser Justin F , Hirsch Joshua A , Hussain M Shazam , Blackham Kristine A , Eskey Clifford J , Jensen Mary E , Moran Christopher J , Prestigiacomo Charles Joseph , Rasmussen Peter A , McDougall Cameron G
Published: November 2011

These guidelines were developed by consensus of a multidisciplinary panel of specialists interested in the evaluation and treatment of patients with arteriovenous malformations (AVMs) of the CNS. The reporting criteria described will serve as a template for trial design and for clinical investigators who wish to report on endovascular therapy of cerebral AVMs. Direct comparison of various treatment paradigms is important to standardization of care, maximization of good treatment outcomes, assessment of new methods and technologies.
VARIATIONAL QUANTUM TOMOGRAPHY WITH INCOMPLETE INFORMATION BY MEANS OF SEMIDEFINITE PROGRAMS
Authors: MACIEL THIAGO O. , CESÁRIO ANDRÉ T. , VIANNA REINALDO O.
Published: November 2011

We introduce a new method to reconstruct unknown quantum states out of incomplete and noisy information. The method is a linear convex optimization problem, therefore with a unique minimum, which can be efficiently solved with Semidefinite Programs. Numerical simulations indicate that the estimated state does not overestimate purity, and neither the expectation value of optimal entanglement witnesses. The convergence properties of the method are similar to compressed sensing approaches, in the sense that, in order to reconstruct low rank states, it needs just a fraction of the effort corresponding to an informationally complete measurement.
GAUGE-INVARIANT EXTENSION OF LINEARIZED HORAVA GRAVITY
Authors: DAS SUDIPTA , GHOSH SUBIR
Published: November 2011

In this paper we have constructed a gauge-invariant extension of a generic Horava Gravity (HG) model (with quadratic curvature terms) in linearized version in a systematic procedure. No additional fields are introduced. The linearized HG model is explicitly shown to be a gauge fixed version of the Einstein Gravity (EG) thus proving the Bellorin–Restuccia conjecture in a robust way. In the process we have explicitly computed the correct Hamiltonian dynamics using Dirac Brackets appearing from the Second Class Constraints present in the HG model. We comment on applying this scheme to the full nonlinear HG.
Targeted delivery of vitamin D to the colon using β-glucuronides of vitamin D: therapeutic effects in a murine model of inflammatory bowel disease
Authors: Goff Jesse P. , Koszewski Nicholas J. , Haynes Joseph S. , Horst Ronald L.
Published: November 2011

1,25-Dihydroxyvitamin D3[1,25(OH)2D] has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether β-glucuronides of vitamin D could deliver 1,25(OH)2D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH)2D from 1,25-dihydroxyvitamin D3-25-β-glucuronide [β-gluc-1,25(OH)2D]. We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of β-gluc-1,25(OH)2D than 1,25(OH)2D, demonstrating targeted delivery of 1,25(OH)2D to the colon. We then tested β-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH)2D or β-gluc-1,25(OH)2D, severity of colitis was reduced. Combination of β-gluc-1,25(OH)2D with 25-hydroxyvitamin D3-25-β-glucuronide [β-gluc-25(OH)D] resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with β-gluc-1,25(OH)2D alone or in combination with β-gluc-25(OH)D than in mice treated with 1,25(OH)2D, which were hypercalcemic at the time of death. β-Glucuronides of vitamin D compounds can deliver 1,25(OH)2D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model.
Defective pulmonary innervation and autonomic imbalance in congenital diaphragmatic hernia
Authors: Lath Nikesh R. , Galambos Csaba , Rocha Alejandro Best , Malek Marcus , Gittes George K. , Potoka Douglas A.
Published: November 2011

Congenital diaphragmatic hernia (CDH) is associated with significant mortality due to lung hypoplasia and pulmonary hypertension. The role of embryonic pulmonary innervation in normal lung development and lung maldevelopment in CDH has not been defined. We hypothesize that developmental defects of intrapulmonary innervation, in particular autonomic innervation, occur in CDH. This abnormal embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. To define patterns of pulmonary innervation in CDH, human CDH and control lung autopsy specimens were stained with the pan-neural marker S-100. To further characterize patterns of overall and autonomic pulmonary innervation during lung development in CDH, the murine nitrofen model of CDH was utilized. Immunostaining for protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (a sympathetic marker), vesicular acetylcholine transporter (a parasympathetic marker), or VIP (a parasympathetic marker) was performed on lung whole mounts and analyzed via confocal microscopy and three-dimensional reconstruction. Peribronchial and perivascular neuronal staining pattern is less complex in human CDH than control lung. In mice, protein gene product 9.5 staining reveals less complex neuronal branching and decreased neural tissue in nitrofen-treated lungs from embryonic day 12.5 to 16.5 compared with controls. Furthermore, nitrofen-treated embryonic lungs exhibited altered autonomic innervation, with a relative increase in sympathetic nerve staining and a decrease in parasympathetic nerve staining compared with controls. These results suggest a primary defect in pulmonary neural developmental in CDH, resulting in less complex neural innervation and autonomic imbalance. Defective embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH.
Ascorbate protects against vascular leakage in cecal ligation and puncture-induced septic peritonitis
Authors: Zhou Gang , Kamenos George , Pendem Suresh , Wilson John X. , Wu Feng
Published: November 2011

Vascular leakage in multiple organs is a characteristic pathological change in sepsis. Our recent study revealed that ascorbate protects endothelial barrier function in microvascular endothelial cell monolayers through inhibiting serine/threonine protein phosphatase 2A (PP2A) activation (Han M, Pendem S, Teh SL, Sukumaran DK, Wu F, Wilson JX. Free Radic Biol Med 48: 128–135, 2010). The present study addressed the mechanism of protection by ascorbate against vascular leakage in cecal ligation and puncture (CLP)-induced septic peritonitis in mice. CLP caused NADPH oxidase activation and endothelial nitric oxide synthase (eNOS) uncoupling to produce superoxide, increased NO production by inducible NOS (iNOS) and neuronal NOS (nNOS) activity, and elevated 3-nitrotyrosine (a product of peroxynitrite) formation and PP2A activity in the hindlimb skeletal muscles at 12 h after CLP. The increase in PP2A activity was associated with decreased levels of phosphorylated serine and threonine in occludin, which was immunoprecipitated from freshly harvested endothelial cells of the septic skeletal muscles. Moreover, CLP increased the vascular permeability to fluorescent dextran and Evans blue dye in skeletal muscles. An intravenous bolus injection of ascorbate (200 mg/kg body wt), given 30 min prior to CLP, prevented eNOS uncoupling, attenuated the increases in iNOS and nNOS activity, decreased 3-nitrotyrosine formation and PP2A activity, preserved the phosphorylation state of occludin, and completely inhibited the vascular leakage of dextran and Evans blue. A delayed ascorbate injection, given 3 h after CLP, also prevented the vascular permeability increase. We conclude that ascorbate injection protects against vascular leakage in sepsis by sequentially inhibiting excessive production of NO and superoxide, formation of peroxynitrite, PP2A activation, and occludin dephosphorylation. Our study provides a scientific basis for injection of ascorbate as an adjunct treatment for vascular leakage in sepsis.
Compensatory hyperhidrosis following thoracic sympathectomy: a biophysical rationale
Authors: Cramer Matthew N. , Jay Ollie
Published: November 2011

A side-effect of endoscopic thoracic sympathectomy (ETS) is compensatory hyperhidrosis (CH), characterized by excessive sweating from skin areas with intact sudomotor function. The physiological mechanism of CH is unknown, but may represent an augmented local sweat rate from skin areas with uninterrupted sympathetic innervation based on evaporative heat balance requirements. For a given combination of activity and climate, the same absolute amount of evaporation (if any) is needed to balance the rate of metabolic heat production both pre- and post-ETS. However, the rate of local sweating per unit of skin surface area with intact sudomotor activity must be greater post-ETS as evaporation must be derived from a smaller skin surface area. Under conditions with high evaporative requirements, greater degradations in sweating efficiency associated with an increased dripping of sweat should also occur post-ETS, further pronouncing the sweat rate required for heat balance. In conclusion, in addition to the potential role of psychological stimuli for increased sudomotor activity, the existence of CH post-ETS can be described by the interplay between fundamental thermoregulatory physiology and altered heat balance biophysics and does not require a postoperative alteration in physiological control.
Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones
Authors: McHale Matthew J. , Sarwar Zaheer U. , Cardenas Damon P. , Porter Laurel , Salinas Anna S. , Michalek Joel E. , McManus Linda M. , Shireman Paula K.
Published: November 2011

Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E2) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased ( P < 0.001) in ovariectomized mice with high-dose E2 replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater ( P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased ( P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E2, but not P4, replacement decreased ( P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E2 decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury.
Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease
Authors: Elmarakby Ahmed A.
Published: November 2011

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.
Endogenous adenosine contributes to renal sympathetic neurotransmission via postjunctional A1receptor-mediated coincident signaling
Authors: Jackson Edwin K. , Cheng Dongmei , Tofovic Stevan P. , Mi Zaichuan
Published: November 2011

Adenosine A1receptor antagonists have diuretic/natriuretic activity and may be useful for treating sodium-retaining diseases, many of which are associated with increased renal sympathetic tone. Therefore, it is important to determine whether A1receptor antagonists alter renal sympathetic neurotransmission. In isolated, perfused rat kidneys, renal vasoconstriction induced by renal sympathetic nerve simulation was attenuated by 1) 1,3-dipropyl-8-p-sulfophenylxanthine (xanthine analog that is a nonselective adenosine receptor antagonist, but is cell membrane impermeable and thus does not block intracellular phosphodiesterases), 2) xanthine amine congener (xanthine analog that is a selective A1receptor antagonist), 3) 1,3-dipropyl-8-cyclopentylxanthine (xanthine analog that is a highly selective A1receptor antagonist), and 4) FK453 (nonxanthine analog that is a highly selective A1receptor antagonist). In contrast, FR113452 (enantiomer of FK453 that does not block A1receptors), MRS-1754 (selective A2Breceptor antagonist), and VUF-5574 (selective A3receptor antagonist) did not alter responses to renal sympathetic nerve stimulation, and ZM-241385 (selective A2Areceptor antagonist) enhanced responses. Antagonism of A1receptors did not alter renal spillover of norepinephrine. 2-Chloro- N6-cyclopentyladenosine (highly selective A1receptor agonist) increased renal vasoconstriction induced by exogenous norepinephrine, an effect that was blocked by 1,3-dipropyl-8-cyclopentylxanthine, U73122 (phospholipase C inhibitor), GF109203X (protein kinase C inhibitor), PP1 (c-src inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), and OSU-03012 (3-phosphoinositide-dependent protein kinase-1 inhibitor). These results indicate that adenosine formed during renal sympathetic nerve stimulation enhances the postjunctional effects of released norepinephrine via coincident signaling and contributes to renal sympathetic neurotransmission. Likely, the coincident signaling pathway is: phospholipase C → protein kinase C → c-src → phosphatidylinositol 3-kinase → 3-phosphoinositide-dependent protein kinase-1.
Local small airway epithelial injury induces global smooth muscle contraction and airway constriction
Authors: Zhou Jian , Alvarez-Elizondo Martha B. , Botvinick Elliot , George Steven C.
Published: November 2011

Small airway epithelial cells form a continuous sheet lining the conducting airways, which serves many functions including a physical barrier to protect the underlying tissue. In asthma, injury to epithelial cells can occur during bronchoconstriction, which may exacerbate airway hyperreactivity. To investigate the role of epithelial cell rupture in airway constriction, laser ablation was used to precisely rupture individual airway epithelial cells of small airways (<300-μm diameter) in rat lung slices (∼250-μm thick). Laser ablation of single epithelial cells using a femtosecond laser reproducibly induced airway contraction to ∼70% of the original cross-sectional area within several seconds, and the contraction lasted for up to 40 s. The airway constriction could be mimicked by mechanical rupture of a single epithelial cell using a sharp glass micropipette but not with a blunt glass pipette. These results suggest that soluble mediators released from the wounded epithelial cell induce global airway contraction. To confirm this hypothesis, the lysate of primary human small airway epithelial cells stimulated a similar airway contraction. Laser ablation of single epithelial cells triggered a single instantaneous Ca2+wave in the epithelium, and multiple Ca2+waves in smooth muscle cells, which were delayed by several seconds. Removal of extracellular Ca2+or decreasing intracellular Ca2+both blocked laser-induced airway contraction. We conclude that local epithelial cell rupture induces rapid and global airway constriction through release of soluble mediators and subsequent Ca2+-dependent smooth muscle shortening.
The Lichfield bone study: the skeletal response to exercise in healthy young men
Authors: Eleftheriou Kyriacos I. , Rawal Jaikirty S. , Kehoe Anthony , James Laurence E. , Payne John R. , Skipworth James R. , Puthucheary Zudin A. , Drenos Fotios , Pennell Dudley J. , Loosemore Mike , World Michael , Humphries Steve E. , Haddad Fares S. , Montgomery Hugh E.
Published: November 2011

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% ( P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively ( P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm3, P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm3, P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm3, P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.
Local sensitivity to stimulus orientation and spatial frequency within the receptive fields of neurons in visual area 2 of macaque monkeys
Authors: Tao X. , Zhang B. , Smith E. L. , Nishimoto S. , Ohzawa I. , Chino Y. M.
Published: November 2011

We used dynamic dense noise stimuli and local spectral reverse correlation methods to reveal the local sensitivities of neurons in visual area 2 (V2) of macaque monkeys to orientation and spatial frequency within their receptive fields. This minimized the potentially confounding assumptions that are inherent in stimulus selections. The majority of neurons exhibited a relatively high degree of homogeneity for the preferred orientations and spatial frequencies in the spatial matrix of facilitatory subfields. However, about 20% of all neurons showed maximum orientation differences between neighboring subfields that were greater than 25 deg. The neurons preferring horizontal or vertical orientations showed less inhomogeneity in space than the neurons preferring oblique orientations. Over 50% of all units also exhibited suppressive profiles, and those were more heterogeneous than facilitatory profiles. The preferred orientation and spatial frequency of suppressive profiles differed substantially from those of facilitatory profiles, and the neurons with suppressive subfields had greater orientation selectivity than those without suppressive subfields. The peak suppression occurred with longer delays than the peak facilitation. These results suggest that the receptive field profiles of the majority of V2 neurons reflect the orderly convergence of V1 inputs over space, but that a subset of V2 neurons exhibit more complex response profiles having both suppressive and facilitatory subfields. These V2 neurons with heterogeneous subfield profiles could play an important role in the initial processing of complex stimulus features.
Nonlinearity of two-photon Ca2+imaging yields distorted measurements of tuning for V1 neuronal populations
Authors: Nauhaus Ian , Nielsen Kristina J. , Callaway Edward M.
Published: November 2011

We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates. The observed relationship is consistent with saturation that clips the high-contrast tuning curve peaks by ∼40%. The nonlinearity was also apparent in mouse V1 responses to drifting gratings, but not as strong as in the ferret. Contrast invariance holds, however, for tuning curves measured with a randomized grating stimulus. This finding is consistent with prior work showing that the linear portion of a linear-nonlinear system can be recovered with reverse correlation. Furthermore, we demonstrate that a noise stimulus is more effective at keeping spike rates in the linear operating regime of a saturating nonlinearity, which both maximizes signal-to-noise ratios and simplifies the recovery of fast spike dynamics from slow calcium transients. Finally, we uncover spatiotemporal receptive fields by removing the nonlinearity and slow calcium transient from a model of fluorescence generation, which allowed us to observe dynamic sharpening of orientation tuning. We conclude that for two-photon recordings it is imperative that one considers the nonlinear distortion when designing stimuli and interpreting results, especially in sensory areas, species, or cell types with high firing rates.
Increasing the Understanding and Demonstration of Appropriate Affection in Children with Asperger Syndrome: A Pilot Trial
Authors: Sofronoff Kate , Eloff Johann , Sheffield Jeanie , Attwood Tony
Published: November 2011

The study was conducted to examine relationships between affectionate behavior in children with Asperger syndrome and variables likely to influence its expression (e.g., tactile sensitivity, social ability). It also evaluated the impact of a cognitive behavioral intervention that aimed to improve a child's understanding and expression of affection. Twenty-one children, aged 7 to 12 years, participated in the trial. The results showed significant correlations between measures of affection and tactile sensitivity and social ability. After attending the 5-week program, parents identified significant increases in the appropriateness of children's affectionate behavior both towards immediate family and people outside the immediate family, despite reporting no significant changes in their child's general difficulties with affectionate behavior. There was a significant improvement in children's understanding of the purpose of affection. The findings are discussed as well as the limitations of the study.
The Factors That May Predict Response to Rituximab Therapy in Recurrent Focal Segmental Glomerulosclerosis: A Systematic Review
Authors: Araya Carlos E. , Dharnidharka Vikas R.
Published: November 2011

Recurrence of FSGS occurs in 30–40% of allografts. Therapies for recurrence are not well established. We retrieved all published reports depicting kidney transplant recipients with focal segmental glomerulosclerosis (FSGS) recurrence, treated with rituximab, to determine factors associated with treatment response. We found 18 reports of 39 transplant recipients who received rituximab. By univariate analysis for two outcomes (no response versus any response), fewer rituximab infusions and normal serum albumin at recurrence were associated with treatment response. For 3 outcomes (no response, partial and complete remission), male gender, fewer rituximab infusions, shorter time to rituximab treatment, and normal serum albumin were associated with remission. Multivariate analysis for both models revealed that normal serum albumin at FSGS recurrence and lower age at transplant were associated with response. Rituximab for recurrence of FSGS may be beneficial for only some patients. A younger age at transplant and normal serum albumin level at recurrence diagnosis may predict response.
Training in EUS-Guided Fine Needle Aspiration: Safety and Diagnostic Yield of Attending Supervised, Trainee-Directed FNA from the Onset of Training
Authors: Coté Gregory A. , Hovis Christine E. , Kohlmeier Cara , Ammar Tarek , Al-Lehibi Abed , Azar Riad R. , Edmundowicz Steven A. , Mullady Daniel K. , Krigman Hannah , Ylagan Lourdes , Hull Michael , Early Dayna S.
Published: November 2011

Background. The optimal time to initiate hands-on training in endoscopic ultrasound fine needle aspiration (EUS-FNA) is unclear. We studied the feasibility of initiating EUS-FNA training concurrent with EUS training. Methods. Three supervised trainees were instructed on EUS-FNA technique and allowed hands-on exposure from the onset of training. The trainee and attending each performed passes in no particular order. During trainee FNA, the attending provided verbal instruction as needed but no hands-on assistance. A blinded cytopathologist assessed the adequacy (cellularity) and diagnostic yield of individual passes. Primary outcomes compared cellularity and diagnostic yield of attending versus fellow FNA passes. Results. We analyzed 305 FNA sites, including pancreas (51.2%), mediastinal/upper abdominal lymph node (LN) (28.5%) and others (20.3%). The average proportion of fellow passes with AC was similar to attending FNA—pancreas: 70.3 versus 68.8%; LN: 79.0 versus 81.7%; others 65.5 versus 68.7%; P > 0.05); these did not change significantly during the training period. Among cases with confirmed malignancy (n = 179), the sensitivity of EUS-FNA was 78.8% (68.4% fellow-only versus 69.6% attending only). There were no EUS-FNA complications. Conclusions. When initiated at the onset of EUS training, attending-supervised, trainee-directed FNA is safe and has comparable performance characteristics to attending FNA.
Axial Skeletal Location Predicts Poor Outcome in Ewing's Sarcoma: A Single Institution Experience
Authors: Weiss Kurt R. , Biau David J. , Bhumbra Rej , Griffin Anthony M. , Blackstein Martin E. , Chung Peter , Catton Charles , O'Sullivan Brian , Ferguson Peter C. , Wunder Jay S.
Published: November 2011

Introduction. Ewing's sarcomas (EWSs) of bone and soft tissue are neuroectodermal tumors that affect both axial and appendicular locations. We hypothesized that axial location predicted poor outcome in EWS patients.Materials and Methods. Sixty-seven patients (57 with bone EWS and 10 with soft tissue EWS) were identified from our database. Thirty-four (51%) had axial EWS and 33 (49%) had appendicular EWS. Statistical analyses identified predictors of poor outcome.Results and Discussion. Axial location, large size, metastases at presentation, lack of definitive treatment, and positive surgical margins all correlated with poor outcome in univariate analysis. In multivariate analysis, axial location still predicted poor outcome when adjusted for pretreatment variables. Axial location was not statistically predictive of poor outcome when adjusted for treatment variables.Conclusions. Anatomic location has a negative effect on outcome in EWS that cannot be completely explained by pretreatment or treatment factors. Additional studies are required to determine if there is a biologic difference between axial and appendicular EWS.
Cardiac Arrest Caused by Multiple Recurrent Pulmonary Embolism
Authors: Hannig Kjartan Eskjaer , Husted Steen Elkjaer , Grove Erik Lerkevang
Published: November 2011

Pulmonary embolism is a common condition with a high mortality. We describe a previously healthy 68-year-old male who suffered three pulmonary embolisms during a short period of time, including two embolisms while on anticoagulant treatment. This paper illustrates three important points. (1) The importance of optimal anticoagulant treatment in the prevention of pulmonary embolism reoccurrence. (2) The benefit of immediate accessibility to echocardiography in the handling of haemodynamically unstable patients with an unknown underlying cause. (3) Thrombolytic treatment should always be considered and may be life-saving in patients with cardiac arrest suspected to be caused by pulmonary embolism.
Do Orientation-Based Differences in Nestbox Temperature Cause Differential Ectoparasite Load and Explain Patterns of Nest-Site Selection and Offspring Condition in Great Tits?
Authors: Goodenough Anne E. , Elliot Simon L. , Hart Adam G.
Published: November 2011

Nest ectoparasites have been linked previously to patterns of nest-site choice and breeding success in birds. Recent research has shown nestboxes facing south-southwest are occupied less frequently by great tits (Parus major) than identical boxes facing other directions, and are associated with reduced offspring condition. Here, we investigate the hypothesis that these findings are due to ectoparasite load being directionally nonuniform, possibly because of nonuniformity in nestbox internal temperature. Nests contained, in order of prevalence, hen fleas (Ceratophyllus gallinae), haematophagous blowflies (Protocalliphoraspp.), biting lice (Ischnocera), and ticks/mites (Acari). Although southwest-facing nestboxes were significantly warmer than other boxes, there was no directional difference in total ectoparasite load or abundance of particular species. Similarly, there was no relationship between abundance of any ectoparasite species (either per-nest or per-chick) and avian offspring condition determined using wing length or relative mass. We discuss several possible, nonmutually exclusive, explanations for this, including compensatory responses, costs of parasitism being transferred to parents, and condition-dependent effects.
Imaging Early Steps of Sindbis Virus Infection by Total Internal Reflection Fluorescence Microscopy
Authors: Gu Youling , Yang Yuanzheng , Liu Yuechueng
Published: November 2011

Sindbis virus (SINV) is an alphavirus that has a broad host range and has been widely used as a vector for recombinant gene transduction, DNA-based vaccine production, and oncolytic cancer therapy. The mechanism of SINV entry into host cells has yet to be fully understood. In this paper, we used single virus tracking under total internal reflection fluorescence microscopy (TIRFM) to investigate SINV attachment to cell surface. Biotinylated viral particles were labeled with quantum dots, which retained viral viability and infectivity. By time-lapse imaging, we showed that the SINV exhibited a heterogeneous dynamics on the surface of the host cells. Analysis of SINV motility demonstrated a two-step attachment reaction. Moreover, dual color TIRFM of GFP-Rab5 and SINV suggested that the virus was targeted to the early endosomes after endocytosis. These findings demonstrate the utility of quantum dot labeling in studying the early steps and behavior of SINV infection.
Antimalaria Effect of the Ethanolic Stem Bark Extracts ofFicus platyphyllaDel
Authors: Shittu Isma'il , Emmanuel Amlabu , Nok Andrew Jonathan
Published: November 2011

The antimalarial effect of the ethanolic stem bark extract ofFicus platyphyllaDel was evaluated againstPlasmodium bergheiinfection in mice. Nontreated, experimental control mice died of fulminant parasitemia from day 7 to 9 post-infection but mice treated with the extract at 300 mg/kg showed markedly reduced parasitaemia bouts of 43.50% and a mean survival time of 28 days postinfection. The plant extract prevented a drastic reduction in PCV showing its efficacy in ameliorating anaemic conditions inPlasmodium berghei-infected mice. Histological examination of liver tissues of treated and untreated mice further supports the antimalaria potential of this plant. This observation validates the traditional use of this plant for the treatment of malaria.
Efficacy of Topical Liposomal Amphotericin B versus Intralesional Meglumine Antimoniate (Glucantime) in the Treatment of Cutaneous Leishmaniasis
Authors: Layegh Pouran , Rajabi Omid , Jafari Mahmoud Reza , Emamgholi Tabar Malekshah Parisa , Moghiman Toktam , Ashraf Hami , Salari Roshanak
Published: November 2011

Background. Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis.Aims. The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis.Methods. From 110 patients, the randomly selected 50 received a topical liposomal formulation of amphotericin B into each lesion, 3–7 drops twice daily, according to the lesion's size and for 8 weeks. The other group of 60 patients received intralesional glucantime injection of 1-2 mL once a week for the same period. The clinical responses and side effects of both groups were evaluated weekly during the treatment course.Results. Per-protocol analysis showed no statistically significant difference between the two groups (, 95% confidence interval (0.632–4.101)). Moreover, after intention-to-treat analysis, the same results were seen (, 95% (0.560–2.530)). Serious post treatment side effects were not observed in either group.Conclusions. Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis.
The Serum Level of Fibroblast Growth Factor-23 and Calcium-Phosphate Homeostasis in Obese Perimenopausal Women
Authors: Holecki M. , Chudek J. , Więcek A. , Titz-Bober M. , Duława J.
Published: November 2011

Plasma FGF-23 concentrations and its relationship with calcium-phosphate homeostasis were evaluated in 48 perimenopausal obese women and in 29 nonobese controls. Serum parathyroid hormone, 25-hydroxyvitamin D3, CTX1, osteocalcin, total calcium, phosphorus, creatinine, and plasma intact FGF-23 concentrations were assessed. DXA of lumbar spine and femoral neck was performed to determine bone mineral density (BMD). Plasma iFGF-23 concentration was significantly higher in obese patients (by 42%) and correlated with age and BMD of proximal femur (R=-0.346;R=0.285, resp.) but not with markers of bone turnover. However, serum phosphorus level in obese subjects was significantly lower. iFGF-23 concentration correlated significantly with body mass index (R=0.292) and fat content (R=0.259) in all study subjects. Moreover, a significant correlation between iFGF-23 and iPTH (R=0.254) was found. No correlation between serum phosphorus or eGFR and plasma iFGF-23 and between eGFR and serum phosphorus was found. Elevated serum iFGF-23 concentration may partially explain lower phosphorus levels in the obese and seems not to reflect bone turnover.
Hypoacusia in a Patient Treated by Isotretinoin
Authors: Rosende L. , Verea-Hernando M. M. , de Andrés A. , Piñeyro-Molina F. , Barja J. , Castro-Castro S. , Fonseca E.
Published: November 2011

Isotretinoin is the most effective treatment for severe acne, but there are several adverse effects associated with its use, some of them very exceptional (<1/10000). We report one case of hypoacusia and tinnitus in a 15-year-old boy treated with isotretinoin during 6 weeks, who quickly improved after isotretinoin withdrawal. Also, we comment other publications about hearing alterations in patients treated with isotretinoin and other retinoids.
Identification of Halohydrins as Potential Disinfection By‐Products in Treated Drinking Water
Authors: Jobst Karl J. , Taguchi Vince Y. , Bowen Richard D. , Trikoupis Moschoula A. , Terlouw Johan K.
Published: November 2011

In 2001, two potential disinfection by‐products (DBPs) were tentatively identified as 1‐aminoxy‐1‐chlorobutan‐2‐ol (DBP‐A) and its bromo analogue (DBP‐B) (Taguchi 2001). Subsequently it became clear, by consulting an updated version of the NIST database, that their mass spectra are close to those of the halohydrins 4‐chloro‐2‐methylbutan‐2‐ol and 3‐bromo‐2‐methylbutan‐2‐ol. To establish the structures of these DBPs, additional mass spectrometric experiments, including Fourier transform ion cyclotron resonance (FTICR), were performed on treated drinking water samples and authentic halohydrin standards.
It appears that DBP‐A is 3‐chloro‐2‐methylbutan‐2‐ol and that DBP‐B is its bromo analogue. DBP‐B has been detected in ozonated waters containing bromide. Our study also shows that these DBPs can be laboratory artefacts, generated by the reaction of residual chlorine in the sample with 2‐methyl‐2‐butene, the stabilizer in the CH2Cl2 used for extraction. This was shown by experiments using CH2Cl2 stabilized with deuterium labelled 2‐methyl‐2‐butene. Quenching any residual chlorine in the drinking water sample with sodium thiosulfate minimizes the formation of these artefacts.