Belowground changes to community structure alter methane-cycling dynamics in Amazonia.
Amazonian rainforest is undergoing increasing rates of deforestation, driven primarily by cattle pasture expansion. Forest-to-pasture conversion has been associated with increases in soil methane (CH4) emission. To better understand the drivers of this change, we measured soil CH4 flux, environmental conditions, and belowground microbial community structure across primary forests, cattle pastures, and secondary forests in two Amazonian regions. We show that pasture soils emit high levels of CH4 (mean: 3454.6 ± 9482.3 μg CH4 m-2 d-1), consistent with previous reports, while forest soils on average emit CH4 at modest rates (mean: 9.8 ± 120.5 μg CH4 m-2 d-1), but often act as CH4 sinks. We report that secondary forest soils tend to consume CH4 (mean: -10.2 ± 35.7 μg CH4 m-2 d-1), demonstrating that pasture CH4 emissions can be reversed. We apply a novel computational approach to identify microbial community attributes associated with flux independent of soil chemistry. While this revealed taxa known to produce or consume CH4 directly (i.e. methanogens and methanotrophs, respectively), the vast majority of identified taxa are not known to cycle CH4. Each land use type had a unique subset of taxa associated with CH4 flux, suggesting that land use change alters CH4 cycling through shifts in microbial community composition. Taken together, we show that microbial composition is crucial for understanding the observed CH4 dynamics and that microorganisms provide explanatory power that cannot be captured by environmental variables.


Clinical utility of custom-designed NGS panel testing in pediatric tumors.
Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers. Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed. NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration. Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.


Retroclavicular vs Infraclavicular block for brachial plexus anesthesia: a multi-centric randomized trial.
The coracoid approach is a simple method to perform ultrasound-guided brachial plexus regional anesthesia (RA) but its simplicity is counterbalanced by a difficult needle visualization. We hypothesized that the retroclavicular (RCB) approach is not longer to perform when compared to the coracoid (ICB) approach, and improves needle visualization. This randomized, controlled, non-inferiority trial conducted in two hospitals, included patients undergoing distal upper limb surgery. Patients were randomly assigned to a brachial plexus block (ICB or RCB). The primary outcome was performance time (sum of visualization and needling time), and was analyzed with a non-inferiority test of averages. Depth of sensory and motor blockade, surgical success, total anesthesia time, needle visualization, number of needle passes and complications were also evaluated. Subgroup analysis restricted to patients with higher body mass index was completed. We included 109 patients between September 2016 and May 2017. Mean RCB performance time was 4.8 ± 2.0 min while ICB was 5.2 ± 2.3 min (p = 0.06) with a 95% CI reaching up to 5.8% longer. RCB conferred an ultrasound-needle angle closer to 0° and significantly improved needle visibility after the clavicle was cleared and before local anesthetic administration. No differences were found in the secondary outcomes. Similar results were found in the subgroup analysis. RCB approach for brachial plexus anesthesia was similar to ICB approach in terms of time performance. Needle visibility, which represent an important clinical variable, was superior and angle between needle and ultrasound probe was close to 0° in the RCB group. ClinicalTrials.gov (NCT02913625), registered 26 September 2016.


Crack cocaine and cocaine hydrochloride. Are the differences myth or reality?
To review and discuss the differences and similarities between the use of crack cocaine and cocaine hydrochloride; and to determine how these findings might affect policies on the imprisonment and treatment of cocaine users. English-language publications were identified through a computerized search (using MEDLINE) between 1976 and 1996 using the search terms "smoked cocaine," "crack cocaine," "freebase," and "cocaine-base." In addition, manual searches were conducted on references cited in original research articles, reviews, and an annotated bibliography, and on selected journals. Only those articles that compared various routes of cocaine administration or types of cocaine (cocaine base or crack cocaine vs cocaine hydrochloride) were examined. Studies were reviewed to obtain information on the composition of the 2 forms of cocaine, and the prevalence, pharmacokinetics and pharmacodynamics, abuse liability, pattern of use, and consequences across the various routes of cocaine administration and forms of cocaine. Cocaine hydrochloride is readily converted to base prior to use. The physiological and psychoactive effects of cocaine are similar regardless of whether it is in the form of cocaine hydrochloride or crack cocaine (cocaine base). However, evidence exists showing a greater abuse liability, greater propensity for dependence, and more severe consequences when cocaine is smoked (cocaine-base) or injected intravenously (cocaine hydrochloride) compared with intranasal use (cocaine hydrochloride). The crucial variables appear to be the immediacy, duration, and magnitude of cocaine's effect, as well as the frequency and amount of cocaine used rather than the form of the cocaine. Furthermore, cocaine hydrochloride used intranasally may be a gateway drug or behavior to using crack cocaine. Based on these findings, the federal sentencing guidelines allowing possession of 100 times more cocaine hydrochloride than crack cocaine to trigger mandatory minimum penalties is deemed excessive. Although crack cocaine has been linked with crime to a greater extent than cocaine hydrochloride, many of these crimes are associated with the addiction to cocaine. Therefore, those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison.


Infectious mononucleosis complicated by acute hepatitis and myocarditis: a response to corticosteroids.
Infectious mononucleosis, or glandular fever, is a viral illness which commonly affects young adults. Symptoms can vary from sore throat, enlarged lymph glands, lethargy and weight loss to more serious clinical manifestations such as myocarditis or hepatitis. Treatment is usually conservative although there has been significant debate over the role of oral corticosteroids, especially in more serious cases. Evidence based medicine suggests that there is little to no role for steroids, but there are enough published case reports where steroid therapy has been potentially life saving that the debate continues. We present a case of a fit and well man who had significant multi-organ involvement secondary to infectious mononucleosis, and our experience of oral corticosteroid treatment.


A catalog of single nucleotide changes distinguishing modern humans from archaic hominins.
Throughout the past decade, studying ancient genomes has provided unique insights into human prehistory, and differences between modern humans and other branches like Neanderthals can enrich our understanding of the molecular basis of unique modern human traits. Modern human variation and the interactions between different hominin lineages are now well studied, making it reasonable to go beyond fixed genetic changes and explore changes that are observed at high frequency in present-day humans. Here, we identify 571 genes with non-synonymous changes at high frequency. We suggest that molecular mechanisms in cell division and networks affecting cellular features of neurons were prominently modified by these changes. Complex phenotypes in brain growth trajectory and cognitive traits are likely influenced by these networks and other non-coding changes presented here. We propose that at least some of these changes contributed to uniquely human traits, and should be prioritized for experimental validation.


T cells producing GM-CSF and IL-13 are enriched in the cerebrospinal fluid of relapsing MS patients.
Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune demyelinating disease. Its pathogenesis involves humoral and cellular immunity, with production of pro- and anti-inflammatory cytokines by T cells. To analyze the cytokine profile of cerebrospinal fluid (CSF) T cells in patients with relapsing-remitting MS (RRMS) and non-inflammatory controls. T cell cytokine production was analyzed by flow cytometry in CSF samples collected from 34 untreated RRMS patients and 20 age-matched controls. Immunofluorescence studies were performed in spinal cord MS active lesions. Percentages of CSF-derived IL-17A, IL-17A/IL-22, and IL-17A/GM-CSF producing T cells were significantly higher in RRMS patients compared to controls. Percentages of T cells producing IFN-γ were lower in RRMS patients compared to controls. Patients in relapse showed higher percentages of CD4+ T cells producing IL-13 and GM-CSF compared to patients in remission. We found a positive correlation between percentages of IL-13+ T cells and the Expanded Disability Status Scale (EDSS; ρ = 0.5; p < 0.05). Meningeal IL-13-producing T cells were detected in spinal cord MS active lesions. We observed differences in IL-17, IL-22, and IFN-γ production by CSF T cells in RRMS versus controls and a positive correlation between IL-13-producing T cells and EDSS in RRMS patients.


Culture-Documented Invasive Mold Infections at MD Anderson Cancer Center in Houston, Texas, Pre- and Post-Hurricane Harvey.
Extensive floodwater damage following hurricane Harvey raised concerns of excess mold infections in immunocompromised patients. This study sought to evaluate the impact of hurricane Harvey on the incidence of culture-positive invasive mold infections (cIMIs) in patients treated at MD Anderson Cancer Center (MDACC; Houston, TX). All mold-positive culture results in the Microbiology Laboratory at MDACC in a 12-month period before and after hurricane Harvey were reviewed. cIMI cases were defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Rates and causative agents of cIMIs pre- and post-Harvey were compared. In addition, we evaluated institution-wide trends in the use of systemically administered mold-active antifungal agents by segmented regression analysis. Inpatient cIMI rates per 1000 patient-days were comparable in the pre- and post-Harvey observation period (0.17 vs 0.21, P = .36). During both surveillance periods, the vast majority of cIMI cases were due to Aspergillus spp., Fusarium spp., or Mucorales. No emergence of unusual mold infections was seen, and the relative frequencies of mold genera recovered from cultures at the MDACC Microbiology Laboratory remained largely unaltered. The overall use of posaconazole was significantly higher in the post-Harvey period and the use of both voriconazole and liposomal amphotericin B began to increase significantly immediately after Harvey. Our monocentric study employing stringent culture-based definitions of mold infections found no excess cases of IMIs in MDACC's immunosuppressed patient population in the aftermath of a major flooding event. Increased use of some mold-active antifungals in the aftermath of hurricane Harvey was observed institutionally.


Health Information System in a Cloud Computing Context.
Healthcare as a worldwide industry is experiencing a period of growth based on health information technology. The capabilities of cloud systems make it as an option to develop eHealth goals. The main objectives of the present study was to evaluate the advantages and limitations of health information systems implementation in a cloud-computing context that was conducted as a systematic review in 2016. Science direct, Scopus, Web of science, IEEE, PubMed and Google scholar were searched according study criteria. Among 308 articles initially found, 21 articles were entered in the final analysis. All the studies had considered cloud computing as a positive tool to help advance health technology, but none had insisted too much on its limitations and threats. Electronic health record systems have been mostly studied in the fields of implementation, designing, and presentation of models and prototypes. According to this research, the main advantages of cloud-based health information systems could be categorized into the following groups: economic benefits and advantages of information management. The main limitations of the implementation of cloud-based health information systems could be categorized into the 4 groups of security, legal, technical, and human restrictions. Compared to earlier studies, the present research had the advantage of dealing with the issue of health information systems in a cloud platform. The high frequency of studies conducted on the implementation of cloud-based health information systems revealed health industry interest in the application of this technology. Security was a subject discussed in most studies due to health information sensitivity. In this investigation, some mechanisms and solutions were discussed concerning the mentioned systems, which would provide a suitable area for future scientific research on this issue. The limitations and solutions discussed in this systematic study would help healthcare managers and decision-makers take better and more efficient advantages of this technology and make better planning to adopt cloud-based health information systems.


Children with Hemiparesis Arm and Movement Project (CHAMP): protocol for a multisite comparative efficacy trial of paediatric constraint-induced movement therapy (CIMT) testing effects of dosage and type of constraint for children with hemiparetic cerebral palsy.
The Children with Hemiparesis Arm and Movement Project (CHAMP) addresses two pressing issues concerning paediatric constraint-induced movement therapy (CIMT): effects of two dosages and two types of constraint on functional outcomes. Systematic reviews conclude that CIMT is one of the most efficacious treatments, but wide variations in treatment protocols, outcome measures and patient characteristics have prevented conclusions about potential effects of dosage levels and constraint methods. CHAMP is a multisite comparative efficacy randomised controlled trial of 135 children (2-8 years) with hemiparetic cerebral palsy. The 2×2 factorial design tests two dosage levels-60 hours (3.0 hours/day, 5 days/week × 4 weeks) and 30 hours (2.5 hours/day, 3 days/week × 4 weeks) and two constraint conditions-full-arm, full-time cast and part-time splint, plus usual and customary (UCT) controls, yielding five groups: (1) 60 hours CIMT+full-time cast, (2) 60 hours CIMT+part-time splint, (3) 30 hours CIMT+full-time cast, (4) 30 hours CIMT+part-time splint and (5) UCT. Trained therapists deliver the standardised ACQUIREc protocol for CIMT. Blinded assessments at baseline, end of treatment, and 6 and 12 months post treatment include the Assisting Hand Assessment, and subscales from the Peabody Developmental Motor Scales-2 and modified Quality of Upper Extremity Skills Test. Parents complete the Pediatric Motor Activity Log and Pediatric Evaluation of Disability Inventory. A new Fidelity of Implementation Rehabilitation Measure monitors treatment delivery. Data analyses involve repeated-measures multivariate analysis of co-variance controlling for selected baseline variables. Ethics boards at site universities approved the study protocol. To promote equipoise, parents of UCT controls are offered ACQUIREc after 6 months. A Data Safety and Monitoring Committee reviews results regularly, including measures of child and family stress. We will disseminate CHAMP results via peer-reviewed publications and presentations to professional and advocacy organisations. NCT01895660; Pre-results.


Genetic relationships between clinical isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: characterization of "Atypical" pneumococci and organisms allied to S. mitis harboring S. pneumoniae virulence factor-encoding genes.
The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distinguished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three differentiating characteristics: optochin susceptibility, bile solubility, and agglutination with antipneumococcal polysaccharide capsule antibodies. However, there are many reports in the literature of pneumococci lacking one or more of these defining characteristics. Sometimes called "atypical" pneumococci, these isolates can be the source of considerable confusion in the clinical laboratory. Little is known to date about the genetic relationships of such organisms with classical S. pneumoniae isolates. Here we describe these relationships based on sequence analysis of housekeeping genes in comparison with previously characterized isolates of S. pneumoniae, S. mitis, and S. oralis. While most pneumococci were found to represent a closely related group these studies identified a subgroup of atypical pneumococcal isolates (bile insoluble and/or "acapsular") distinct from, though most closely related to, the "typical" pneumococcal isolates. However, a large proportion of isolates, found to be atypical on the basis of capsule reaction alone, did group with typical pneumococci, suggesting that they have either lost capsule production or represent as-yet-unrecognized capsular types. In contrast to typical S. pneumoniae, isolates phenotypically identified as S. mitis and S. oralis, which included isolates previously characterized in taxonomic studies, were genetically diverse. While most of the S. oralis isolates did fall into a well-separated group, S. mitis isolates did not cluster into a well-separated group. During the course of these studies we also identified a number of potentially important pathogenic isolates, which were frequently associated with respiratory disease, that phenotypically and genetically are most closely related to S. mitis but which harbor genes encoding the virulence determinants pneumolysin and autolysin classically associated with S. pneumoniae.


SAR image autofocus by sharpness optimization: a theoretical study.
Synthetic aperture radar (SAR) autofocus techniques that optimize sharpness metrics can produce excellent restorations in comparison with conventional autofocus approaches. To help formalize the understanding of metric-based SAR autofocus methods, and to gain more insight into their performance, we present a theoretical analysis of these techniques using simple image models. Specifically, we consider the intensity-squared metric, and a dominant point-targets image model, and derive expressions for the resulting objective function. We examine the conditions under which the perfectly focused image models correspond to stationary points of the objective function. A key contribution is that we demonstrate formally, for the specific case of intensity-squared minimization autofocus, the mechanism by which metric-based methods utilize the multichannel defocusing model of SAR autofocus to enforce the stationary point property for multiple image columns. Furthermore, our analysis shows that the objective function has a special separble property through which it can be well approximated locally by a sum of 1-D functions of each phase error component. This allows fast performance through solving a sequence of 1-D optimization problems for each phase component simultaneously. Simulation results using the proposed models and actual SAR imagery confirm that the analysis extends well to realistic situations.


Quantification of Nitric Oxide Concentration Using Single-Walled Carbon Nanotube Sensors.
Nitric oxide (NO), a free radical present in biological systems, can have many detrimental effects on the body, from inflammation to cancer. Due to NO's short half-life, detection and quantification is difficult. The inability to quantify NO has hindered researchers' understanding of its impact in healthy and diseased conditions. Single-walled carbon nanotubes (SWNTs), when wrapped in a specific single-stranded DNA chain, becomes selective to NO, creating a fluorescence sensor. Unfortunately, the correlation between NO concentration and the SWNT's fluorescence intensity has been difficult to determine due to an inability to immobilize the sensor without altering its properties. Through the use of a recently developed sensor platform, systematic studies can now be conducted to determine the correlation between SWNT fluorescence and NO concentration. This paper explains the methods used to determine the equations that can be used to convert SWNT fluorescence into NO concentration. Through the use of the equations developed in this paper, an easy method for NO quantification is provided. The methods outlined in this paper will also enable researchers to develop equations to determine the concentration of other reactive species through the use of SWNT sensors.


Long noncoding RNA mediates stroke-induced neurogenesis.
Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.


Acupuncture for the Treatment of Peripheral Neuropathy: A Systematic Review and Meta-Analysis.
Neuropathy and its associated pain pose great therapeutic challenges. While there has been a recent surge in acupuncture use and research, little remains known about its effects on nerve function. This review aims to assess the efficacy of acupuncture in the treatment of neuropathy of various etiologies. The Medline, AMED, Cochrane, Scopus, CINAHL, and clintrials.gov databases were systematically searched from inception to July 2015. Randomized controlled trials (RCTs) assessing acupuncture's efficacy for poly- and mononeuropathy were reviewed. Parallel and crossover RCTs focused on acupuncture's efficacy were reviewed and screened for eligibility. The Scale for Assessing Scientific Quality of Investigations in Complementary and Alternative Medicine was used to assess RCT quality. RCTs with score of >9 and active control treatments such as sham acupuncture or medical therapy were included. Fifteen studies were included: 13 original RCTs, a long-term follow-up, and a re-analysis of a prior RCT. The selected RCTs studied acupuncture for neuropathy caused by diabetes, Bell's palsy, carpal tunnel syndrome, human immunodeficiency virus (HIV), and idiopathic conditions. Acupuncture regimens, control conditions, and outcome measures differed among studies, and various methodological issues were identified. Still, the majority of RCTs showed benefit for acupuncture over control in the treatment of diabetic neuropathy, Bell's palsy, and carpal tunnel syndrome. Acupuncture is probably effective in the treatment of HIV-related neuropathy, and there is insufficient evidence for its benefits in idiopathic neuropathy. Acupuncture appears to improve nerve conduction study parameters in both sensory and motor nerves. Meta-analyses were conducted on all diabetic neuropathy and Bell's palsy individual subject data (six RCTs; a total of 680 subjects) using a summary estimate random effects model, which showed combined odds ratio of 4.23 (95% confidence interval 2.3-7.8; p < 0.001) favoring acupuncture over control for neuropathic symptoms. Acupuncture is beneficial in some peripheral neuropathies, but more rigorously designed studies using sham-acupuncture control are needed to characterize its effect and optimal use better.


Recently published papers: dying Swans and other stories.
The use of pulmonary artery catheters is under debate yet again. We look at two recent trials evaluating their impact on mortality. Our suspicions regarding obesity are proven and we also look at a simple, cost effective method of reducing ventilator-associated pneumonia. Finally, an intervention to improve the poor outcome associated with out-of hospital cardiac arrests is evaluated.


Sources of health insurance and characteristics of the uninsured: analysis of the March 1998 Current Population Survey.
This Issue Brief provides summary data on the insured and uninsured populations in the nation and in each state. It discusses the characteristics most closely related to individuals' health insurance status. Based on EBRI analysis of the March 1998 Current Population Survey, it represents 1997 data--the most recent data available. In 1997, private or public health insurance, or both, covered 81.7 percent of Americans (193.1 million) at some point. Seventy-one percent of the nonelderly population had private insurance, 64.2 percent through an employment-based plan. Almost 15 percent of the nonelderly had public health insurance. In 1997, 18.3 percent of the nonelderly population was uninsured, compared with 14.8 percent a decade earlier, in 1987. The percentage of uninsured Americans has been increasing since at least 1987. While the increase in the uninsured between 1987 and 1993 can be attributed to the erosion of employment-based health benefits, the portion of Americans covered by employment-based health insurance increased between 1993 (63.5 percent) and 1997 (64.2 percent). The decline in public sources of health insurance would mostly explain the recent increase in the uninsured population. For example, between 1994 and 1996 the percentage of nonelderly Americans covered by CHAMPUS/CHAMPVA declined from 3.8 percent to 2.9 percent, in large part due to downsizing in the military. Similarly, between 1996 and 1997, the percentage of nonelderly Americans covered by Medicaid (the federal-state insurance program for the poor) declined from 12.1 percent to 11.0 percent as people left welfare for the private sector. This follows a decline in Medicaid participation between 1995 and 1996. Between 1996 and 1997 the percentage of nonelderly Americans without health insurance coverage increased from 17.7 percent to 18.3 percent. Further examination indicates that adults ages 18-64 accounted for almost all of this increase. In 1996, 14.8 percent of children and 18.9 percent of persons ages 18-64 were uninsured, compared with 15.0 percent of children and 19.7 percent of persons ages 18-64 in 1997. The decline in Medicaid coverage among nonworking and working adults appears to account for the overall increase in the uninsured. Employment and income play a dominant role in determining an individual's likelihood of having health insurance. In addition, age, gender, firm size, hours of work, and industry are all important determinants of an individual's likelihood of having coverage; however, these variables are also closely linked to employment status and income. Some of the widest variations involve factors that are not always examined in traditional demographic assessments, such as citizenship. However, variations by race, ethnicity, and citizenship are also closely linked to employment status and income.


Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS).
There has been considerable interest in trialing NBS in a range of neurological conditions, and in parallel the range of NBS techniques available continues to expand. Underpinning this is the idea that NBS modulates neuroplasticity and that plasticity is an important contributor to functional recovery after brain injury and to the pathophysiology of neurological disorders. However while the evidence for neuroplasticity and its varied mechanisms is strong, the relationship to functional outcome is less clear and the clinical indications remain to be determined. To be maximally effective, the application of NBS techniques will need to be refined to take into account the diversity of neurological symptoms, the fundamental differences between acute, longstanding and chronic progressive disease processes, and the differential part played by functional and dysfunctional plasticity in diseases of the brain and spinal cord.


Hypnotizability and traumatic experience: a diathesis-stress model of dissociative symptomatology.
The authors propose a diathesis-stress model to describe how pathological dissociation may arise from an interaction between innate hypnotizability and traumatic experience. To support the proposition that pathological dissociation may reflect autohypnotic process, the authors highlight clinical and research data indicating parallels between controlled hypnotic dissociative states and uncontrolled pathological dissociative symptoms and summarize evidence of hypnotizability in persons with psychiatric disorders that manifest these symptoms. The authors present this evidence by examining dissociative symptomatology in four psychological domains: perception, behavior and will, affect, and memory and identity. In addition, modern cognitive and neuropsychological models of dissociation are briefly reviewed. Several lines of evidence converge in support of the role of autohypnosis in pathological dissociation. There is considerable evidence that controlled formal hypnosis can produce a variety of dissociations of awareness and control that resemble many of the symptoms in uncontrolled pathological dissociative conditions; and it is possible to discern in dissociative pathology the features of absorption, dissociation, and suggestibility/automaticity that characterize formal hypnotic states. There is also accumulating evidence of high levels of hypnotic capacity in all groups with dissociative symptomatology that have been systematically assessed. In addition, the widespread and successful therapeutic use of hypnosis in the treatment of many dissociative symptoms and conditions (and the potential for hypnosis to induce dissociative symptomatology) also supports the assumption that hypnosis and pathological dissociation share an underlying process. High hypnotizability may be a diathesis for pathological dissociative states, particularly under conditions of acute traumatic stress.


Influence of head trauma on outcome following anterior temporal lobectomy.
There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.


Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells.
Mice given multiple doses of sublethal irradiation to both the thymus and the peripheral lymphoid tissues showed major transient, and some persistent disruptions in general thymic architecture and in thymic stromal components. At 2 wk after total lymphoid irradiation (TLI), the thymus lacked identifiable medullary regions by immunohistochemical analyses. Medullary stromal cells expression MHC Ag or a medullary epithelial cell Ag, as well as medullary macrophages, were undetectable. Instead, the processes of cortical epithelial cells were observed throughout the entire thymus. Strikingly, thymocyte subsets with mature phenotypes (CD4+CD8- and CD4-CD8+) were present in the apparent absence of a medulla. This early, gross effect was rapidly reversed such that by 1 to 2 mo after TLI, medullary areas with MHC Ag-positive cells were evident. However, abnormalities in a subset of medullary stromal cells appeared to be more persistent. Medullary epithelial cells, identified by the MD1 mAb, were greatly reduced in number and abnormally organized for at least 4 mo after TLI. In addition, macrophages containing endogenous peroxidase activity, normally abundant in medullary regions, were undetectable at all times examined after TLI. Therefore, this irradiation regimen induced both transient and long term effects in the thymus, primarily in medullary regions. These results suggest that TLI may be used as an experimental tool for studying the impact of selective depletion of medullary stromal cells on the development of specific T cell functions.


Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors.
Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies.


Cocaine addiction as a neurological disorder: implications for treatment.
Clinical and preclinical studies provide convincing evidence for persistent neurological/psychiatric impairments and possible neuronal degeneration associated with chronic cocaine/stimulant abuse. These impairments include multifocal and global cerebral ischemia, cerebral hemorrhages, infarctions, optic neuropathy, cerebral atrophy, cognitive impairments, and mood and movement disorders. These findings may encourage the placement of stimulant addiction into the category of organic brain disorders. Functional and microanatomical anomalies in the frontal and temporal cortex as well as other brain regions may be responsible for certain aspects of phenomenology and neuropsychopathology that are characteristic of stimulant polydrug addictions. These may include broad spectrum of deficits in cognition, motivation, and insight; behavioral disinhibition; attention deficits; emotional instability; impulsiveness; aggressiveness; depression; anhedonia; and persistent movement disorders. Although it is still debated whether the hypofrontality and other brain anomalies observed in stimulant abusers are a consequence or an antecedent of drug abuse, this debate seems purely academic and irrelevant with respect to the importance of compensating for these deficits in the development of treatment strategies. The neuropsychiatric impairments accompanying stimulant abuse may contribute to the very high rate of relapse in addicts that can take place after long periods (years) of abstinence. It is possible that the neurological deficits present in stimulant addicts, whether they are primary or secondary to stimulant abuse, are responsible for perpetual drug abuse which may be a form of self-medication (Weiss et al. 1991, 1992). In this context, addiction to stimulants, once fully developed, may represent a true biological dependency on drugs that temporarily compensate for existing neurological deficits. The concept of self-medication by drug addicts is supported by major theories of biological psychiatry. While a majority of drug addicts are polydrug users, there seems to be a preference for a particular type of drug among different populations of addicts. Addicts who experience distress, anxious dysphoria, and turbulent anger prefer the calming actions of opiates, whereas addicts with preceding attention deficit disorder, depression, or bipolar disorder often prefer stimulants (Khantzian 1985). Figure 1 presents conceptual relationships between brain damage and cocaine/stimulant abuse. More clinical studies are needed to establish unequivocally the epidemiological relationships between preexisting neurological deficits-resulting either from genetic, developmental, traumatic, or neurotoxic factors- and vulnerability to drug addictions. Nonetheless, deducing from the results of preclinical studies, it is conceivable that individuals with neurological deficits associated with attention deficit disorder, developmental neuroanatomical abnormalities, lead poisoning, alcoholism, posttraumatic brain lesions, and PTSD may be more vulnerable to stimulant addiction. This notion has significant empirical support as preclinical studies have shown that animals with lesioned prefrontal cortex became supersensitive to cocaine (Schenk et al. 1991) and animals with lesions at the amygdala, VTA, or raphe nuclei manifest more rapid acquisition of amphetamine self-administration than control rats (Deminiere et al. 1989). The above arguments, postulating neuropathology as an intrinsic component of stimulant addiction, should be taken into consideration with the caveat that the clinical manifestations of the disease are heterogenous and addicts may express varying stages and degrees of the disease as determined by environmental and genetic factors. Therefore, it is likely that stimulant addicts who have less advanced neuropathology may recover spontaneously after detoxification with proper nutritional and psychotherapeutic support if they can sustain abstinence. (ABSTR


Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain.
1. We wished to determine whether there are differences in the spatial pattern and intensity of synaptic activity within the conscious human forebrain when different forms and intensities of innocuous and noxious thermal stimuli are experienced. Accordingly, positron emission tomography (PET) with intravenous injection of H2(15)O was used to detect increases in regional cerebral blood flow (rCBF) in normal humans as they discriminated differences in the intensity of noxious and innocuous thermal stimulation applied to the nondominant (left) arm. After stereotactic registration, subtraction images were formed from each subject by subtracting counts of emissions obtained during lower-intensity stimulation from those obtained during stimulation at higher intensities. A statistical summation analysis (Z score) of individual voxels was performed. In addition, volumes of interest were chosen on the basis of a priori hypotheses and the results of previously published PET studies. In both types of analysis, statistical thresholds were established with corrections for multiple comparisons. 2. Twenty-seven subjects were divided into three groups of nine subjects each for the three phases of this investigation. For studies in which repetitive contact heat stimuli were used, each subject was instructed in magnitude estimation on the basis of a scale for which 0 indicated "no heat sensation," 7 "just barely painful," and 10 "just barely tolerable." For the study of pain elicited by immersion of the hand in cold water, subjects were instructed to use a scale in which 0 represented "no pain" and 10 represented just barely tolerable pain. 3. In the warm-discrimination study, two intensities of innocuous heat (36 and 43 degrees C) were applied with a thermode as repetitive 5-s contacts to the volar forearm for a total of approximately 100 s, 8 stimuli before and 12 during each scan. Each temperature was applied on alternate scans for a total of four scans per subject. Neither stimulus was rated painful. All subjects discriminated the 43 degrees C stimulus (average rating 5.90 +/- 1.43, mean +/- SD) from the 36 degrees C stimulus (1.96 +/- 1.08, mean +/- SD; t = 13.19, P < 0.0001). Significant increases in rCBF to the 43 degrees C stimuli were found in the contralateral ventral posterior thalamus, lenticular nucleus, medial prefrontal cortex (Brodmann's areas 10 and 32), and cerebellar vermis. 4. The procedure for discriminating between noxious and innocuous heat stimuli was identical to that used for warm discrimination except that the stimulation temperatures were 40 and 50 degrees C. All subjects rated the 50 degrees C stimuli as painful (average rating 8.9 +/- 0.9, mean +/- SD) and the 40 degrees C stimuli as warm, but not painful (2.1 +/- 1.0). Significant rCBF increases to 50 degrees C stimuli were found contralaterally in the thalamus, anterior cingulate cortex, premotor cortex, and secondary somatosensory (S2) and posterior insular cortices. Significant activity also appeared within the region of the contralateral anterior insula and lenticular nucleus. The ipsilateral premotor cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis, also showed significant rCBF increases. Cerebral blood flow (CBF) increases just below the threshold for statistical significance were seen in the contralateral sensorimotor cortex [primary motor cortex (M1)/primary somatosensory cortex (S1)]. 5. For discrimination between tonic innocuous cold and tonic cold pain, the left hand was immersed to the wrist, throughout each of six scans, in water kept at an average temperature of either 20.5 +/- 1.15 degrees C (mean +/- SD) or 6.02 +/- 1.18 degrees C (mean +/- SD) on alternate scans. All subjects rated the intensity of the stimuli on a scale in which 0 indicated no pain and 10 represented barely tolerable pain. Subjects rated the 20 degrees C water immersion as painless (average rating 0.18 +/- 0.48, mean +/- SD), but gave ratings indicating i


The Intestinal Microbiota of Hermetia illucens Larvae Is Affected by Diet and Shows a Diverse Composition in the Different Midgut Regions.
The larva of the black soldier fly (Hermetia illucens) has emerged as an efficient system for the bioconversion of organic waste. Although many research efforts are devoted to the optimization of rearing conditions to increase the yield of the bioconversion process, microbiological aspects related to this insect are still neglected. Here, we describe the microbiota of the midgut of H. illucens larvae, showing the effect of different diets and midgut regions in shaping microbial load and diversity. The bacterial communities residing in the three parts of the midgut, characterized by remarkable changes in luminal pH values, differed in terms of bacterial numbers and microbiota composition. The microbiota of the anterior part of the midgut showed the highest diversity, which gradually decreased along the midgut, whereas bacterial load had an opposite trend, being maximal in the posterior region. The results also showed that the influence of the microbial content of ingested food was limited to the anterior part of the midgut, and that the feeding activity of H. illucens larvae did not significantly affect the microbiota of the substrate. Moreover, a high protein content compared to other macronutrients in the feeding substrate seemed to favor midgut dysbiosis. The overall data indicate the importance of taking into account the presence of different midgut structural and functional domains, as well as the substrate microbiota, in any further study that aims at clarifying microbiological aspects concerning H. illucens larval midgut.IMPORTANCE The demand for food of animal origin is expected to increase by 2050. Since traditional protein sources for monogastric diets are failing to meet the increasing demand for additional feed production, there is an urgent need to find alternative protein sources. The larvae of Hermetia illucens emerge as efficient converters of low-quality biomass into nutritionally valuable proteins. Many studies have been performed to optimize H. illucens mass rearing on a number of organic substrates and to quantitatively and qualitatively maximize the biomass yield. On the contrary, although the insect microbiota can be fundamental for bioconversion processes and its characterization is mandatory also for safety aspects, this topic is largely overlooked. Here, we provide an in-depth study of the microbiota of H. illucens larval midgut, taking into account pivotal aspects, such as the midgut spatial and functional regionalization, as well as microbiota and nutrient composition of the feeding substrate.


Copper(i)-catalysed asymmetric allylic reductions with hydrosilanes.
A copper(i)-catalysed asymmetric allylic reduction enables a regio- and stereoselective transfer of a hydride nucleophile in an SN2'-fashion onto allylic bromides. This transformation represents a conceptually orthogonal approach to allylic substitution reactions with carbon nucleophiles. A copper(i) complex based upon a chiral N-heterocyclic carbene (NHC) ligand allows for stereoselectivity reaching 99% ee. The catalyst enables a stereoconvergent reaction irrespective of the double bond configuration of the starting materials.


How labour intensive is a doctor-based delivery model for antiretroviral treatment (ART)? Evidence from an observational study in Siem Reap, Cambodia.
Funding for scaling-up antiretroviral treatment (ART) in low-income countries has increased substantially, but the lack of human resources for health (HRH) is increasingly being identified as an important constraint for scaling-up ART. In a clinic run by Médecins Sans Frontières in Siem Reap, Cambodia, we documented the use of doctor-time for ART in September 2004 and in August 2005, for different phases in ART (pre-ART, ART initiation, ART follow-up Year 1, & ART follow-up Year 2). Based on these observations and using a variety of assumptions for survival of patients on ART (between 90 and 95% annually) and for further reductions in doctor-time per patient (between 0 and 10% annually), we estimated the need for doctors for the period 2004 till 2013 in the Siem Reap clinic, and in a hypothetical district in sub-Saharan Africa. In the Siem Reap clinic, we found that from 2004 to 2005 the doctor-time needed per patient was reduced by between 14% and 33%, thanks to a reduction in number of visits per patient and shorter consultation times. In 2004, 2.06 full-time equivalent (FTE) doctors were needed for 522 patients on ART, and in 2005 this was slightly reduced to 1.97 FTE doctors for 911 patients on ART. By 2013, Siem Reap clinic will need between 2 and 5 FTE doctors for ART. In a district in sub-Saharan Africa with 200,000 inhabitants and 20% adult HIV prevalence, using a similar doctor-based ART delivery model, between 4 and 11 FTE doctors would be needed to cover 50% of ART needs. ART is labour intensive. Important reductions in doctor-time per patient can be realized during scaling-up. The doctor-based ART delivery model analysed seems adequate for Cambodia. However, for many districts in sub-Saharan Africa a doctor-based ART delivery model may be incompatible with their HRH constraints.


Liver transplantation in patients with situs inversus.
Seven patients with situs inversus abdominis and one with situs inversus totalis underwent liver transplantation; all are alive at follow-up of between 7 months and 5 years. Two patients required retransplantation within the first 3 weeks (for primary non-function and thrombotic infarction). Seven had additional abnormalities associated with the polysplenia-biliary atresia syndrome. Liver transplantation in these patients involved selection of relatively small donor organs or use of reduced-size grafts. Delayed abdominal wall closure was necessary in two patients and all required a modification of the 'piggy-back' technique of suprahepatic vena caval anastomosis to overcome recipient venous anomalies. Biliary drainage by Roux-en-Y choledochojejunostomy was the preferred technique. Although technically challenging, situs inversus is not a contraindication to liver transplantation and patients should expect full recovery.


Nurses' voices: policy, practice and ethics.
This article deals with nurses' ethical concerns raised by the consequences of changes in governmental and institutional policies on nursing practice and patient care. The aims of this project were to explore perspectives of registered nurses who provide or manage direct patient care on policies that affect nursing and patient care, and to provide input to policy makers for the development of more patient-centred policies. Four focus groups were conducted with a total of 36 registered nurse participants. The project team identified major themes that emerged in the analysis of transcripts of the focus group discussions. The four major themes were: effects of policy focused on cost containment, effects on quality of care, effects on patient education and access to needed services, and effects on nurses and nursing. The participants identified primarily negative effects of changes in national health policy and legislation that influence institutional policies on patient care and nursing practice. The effects of identified policy changes raised concerns about meeting nurses' ethical obligations to patients and families. Participants specified key points for consideration by legislators and other policy makers. They viewed nurses who are involved in direct patient care as a critical resource for legislators and other policy makers in the development of public and institutional policies that affect nursing and patient care.


Th17 cells in autoimmune disease: changing the verdict.
Th17 cells and their proinflammatory signature cytokine, IL-17, have recently replaced Th1 cells to be the essential Th effector population in autoimmune disease. This was based on a similar line of evidence that previously destined Th1 cells to be the sole encephalitogenic Th-cell effector type. However, as for the Th1-effector type before, an increasing amount of evidence is accumulating that questions the pivotal role of Th17 cells in autoimmunity. Recently, four high-impact articles were published that clearly show that Th1 and Th17 cells carry encephalitogenic properties, and dominance of either in an autoimmune setting can confer disease. In two mouse models for autoimmune neuroinflammation, it was suggested that Th1 and Th17 cells act in parallel, both exhibiting a different set of effector mechanisms.


Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors.
A randomized crossover study of prophylactic immunoglobulin (IgG) therapy was performed in patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin's lymphoma (NHL). Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously (IV) every 3 weeks for 1 year. They were then switched to the alternative preparation for another year. The number of serious bacterial infections was significantly less (P = .001; Mainland's cross-over method) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L (P = .046; Fisher's exact test).


Phospholipid profile of amniotic fluid in ovine model of congenital diaphragmatic hernia (CDH): the effect of fetal tracheal occlusion.
Fetal endoscopic tracheal occlusion has been proposed as a prenatal intervention to ameliorate congenital diaphragmatic hernia (CDH) prognosis. Tracheal occlusion (TO) prevents pulmonary fluid egress, leading to tissue expansion, reversal of lung hypoplasia, and potential maturation. Fetal lung maturity strongly correlates with amniotic fluid (AF) phospholipidic composition. In this preliminary study, we characterized the AF phospholipidic profile in CDH-induced, TO-treated, and healthy fetal lambs to define the prenatal treatment benefits of TO on lung maturity. CDH induction was performed at 70 days of gestation, TO was carried out at 102 days of gestation, and caesarean section was carried out at 136 days of gestation. AF samples, taken at 102-136 days of gestation, were evaluated using mass spectrometry. The analysis focused on phosphatidylcholines (PCs) and sphingomyelins (SMs). The most abundant phosphatidylcholine species retrieved in healthy AF was POPC [PC(18:1/16:0)], while the level of DPPC [PC(16:0/16:0)] was extremely low at both gestational ages. CDH induction caused a decrease in POPC and many other PCs. A substantial return of some PCs, in particular POPC, PC(34:2) and PC(18:0/16:0), to a more physiological level was prompted by TO. SMs were unaltered. The AF phospholipidic profile could provide prenatal prognostic markers of CDH and possible indices of lung maturation after fetal treatment.


She2p is a novel RNA-binding protein that recruits the Myo4p-She3p complex to ASH1 mRNA.
In Saccharomyces cerevisiae, Ash1p is a specific repressor of transcription that localizes exclusively to daughter cell nuclei through the asymmetric localization of ASH1 mRNA. This localization requires four cis-acting localization elements located in the ASH1 mRNA, five trans-acting factors, one of which is a myosin, and the actin cytoskeleton. The RNA-binding proteins that interact with these cis-elements remained to be identified. Starting with the 3' most localization element of ASH1 mRNA in the three-hybrid assay, element E3, we isolated a clone corresponding to the C-terminus of She3p. We also found that She3p and She2p interact, and this interaction is essential for the binding of She3p with element E3 in vivo. Moreover, She2p was observed to bind the E3 RNA directly in vitro and each of the ASH1 cis-acting localization elements requires She2p for their localization function. By tethering a She3p-MS2 fusion protein to a reporter RNA containing MS2 binding sites, we observed that She2p is dispensable for She3p-MS2-dependent RNA localization.


Relationship of the posterior cricoarytenoid muscle to the posterior cricoid lamina.
Early experiments in functional electrical stimulation of the posterior cricoarytenoid muscle (PCA) in human beings have involved placement of the electrode along the undersurface of the PCA. The anatomy of the posterior cricoid lamina (PCL) was examined to obtain a quantitative understanding of this region. Thirty fresh-frozen cadaver larynges were dissected. Measurements of the cricoid cartilage and PCA were obtained with a caliper or calibrated probe. Twenty male and 10 female adult larynges were examined. Sex differences were found for the height of the PCL. All larynges had approximately 4 mm of exposed cartilage along the inferior surface of the PCL. The origin of the PCA on the PCL was thinner in the medial-vertical attachment than in the inferior-horizontal. The average inferolateral to superomedial diagonal width of the PCA was 4 mm greater in the male than in the female larynges. Asymmetry between the left and right sides was seen. The PCA can be divided into 2 muscle groups based on its origin on the PCL as well as its insertion into the muscular process of the arytenoid. The quantitative information obtained has implications for electrode design and placement for laryngeal stimulation.


The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling.
Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined. Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference)). The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01). Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.


Bayesian compressive sensing using laplace priors.
In this paper, we model the components of the compressive sensing (CS) problem, i.e., the signal acquisition process, the unknown signal coefficients and the model parameters for the signal and noise using the Bayesian framework. We utilize a hierarchical form of the Laplace prior to model the sparsity of the unknown signal. We describe the relationship among a number of sparsity priors proposed in the literature, and show the advantages of the proposed model including its high degree of sparsity. Moreover, we show that some of the existing models are special cases of the proposed model. Using our model, we develop a constructive (greedy) algorithm designed for fast reconstruction useful in practical settings. Unlike most existing CS reconstruction methods, the proposed algorithm is fully automated, i.e., the unknown signal coefficients and all necessary parameters are estimated solely from the observation, and, therefore, no user-intervention is needed. Additionally, the proposed algorithm provides estimates of the uncertainty of the reconstructions. We provide experimental results with synthetic 1-D signals and images, and compare with the state-of-the-art CS reconstruction algorithms demonstrating the superior performance of the proposed approach.


Effect of gingiva on laser doppler pulpal blood flow measurements.
The purpose of this study was to evaluate the effect of labial and palatinal gingiva on laser Doppler pulpal blood flow measurements. Twenty upper central incisor teeth determined to be vital from 20 volunteers were included into the study. To stabilize the probe, a laboratory-made acrylic splint positioned the probe labially on the cervical third of the tooth crown. We collected measurements without any gingival covering, and under three conditions: after application of an opaque paste on the labial gingiva, the palatal gingiva, or both the labial and palatal gingiva. The measurement values decreased 46% when there was opaque paste on labial gingiva, 10% on palatinal gingiva, and 63% on both. The decrease in the values when there was an opaque paste on palatinal gingiva was not statistically significant (p > 0.05). The differences between all other groups were statistically significant (p < 0.05). In these measurements, the contribution of labial gingiva to laser Doppler pulpal blood flow measurements is more than that of palatinal gingiva.


Feasibility and acceptability of combining cognitive behavioural therapy techniques with swallowing therapy in head and neck cancer dysphagia.
Head and neck cancer squamous cell carcinoma (HNSSC) patients report substantial rates of clinically significant depression and/or anxiety, with dysphagia being a predictor of distress and poorer quality of life. Evidence-based dysphagia interventions largely focus on the remediation of physical impairment. This feasibility study evaluates an intervention which simultaneously uses a psychological therapy approach combined with swallowing impairment rehabilitation. This prospective single cohort mixed-methods study, recruited HNSCC patients with dysphagia, from two institutions. The intervention combined Cognitive Behavioural Therapy with swallowing therapy (CB-EST), was individually tailored, for up to 10 sessions and delivered by a speech and language therapist. Primary acceptability and feasibility measures included recruitment and retention rates, data completion, intervention fidelity and the responsiveness of candidate outcome measures. Measures included a swallowing questionnaire (MDADI), EORTC-QLQH&N35, dietary restrictions scale, fatigue and function scales and the Hospital Anxiety and Depression Scale (HADS), administered pre-, post-CB-EST with three month follow-up and analysed using repeated measures ANOVA. Qualitative interviews were conducted to evaluate intervention processes. A total of 30/43 (70%) eligible patients agreed to participate and 25 completed the intervention. 84% were male, mean age 59 yrs. Patients were between 1 and 60 months (median 4) post-cancer treatment. All patients had advanced stage disease, treated with surgery and radiotherapy (38%) or primary chemoradiotherapy (62%). Pre to post CB-EST data showed improvements in MDADI scores (p = 0.002), EORTC-QLQH&N35 (p = 0.006), dietary scale (p < 0.0001), fatigue (p = 0.002) but no change in function scales or HADS. Barriers to recruitment were the ability to attend regular appointments and patient suitability or openness to a psychological-based intervention. CB-EST is a complex and novel intervention, addressing the emotional, behavioural and cognitive components of dysphagia alongside physical impairment. Preliminary results are promising. Further research is required to evaluate efficacy and effectiveness.


Sialic acid storage diseases. A multiple lysosomal transport defect for acidic monosaccharides.
A defective efflux of free sialic acid from the lysosomal compartment has been found in the clinically heterogeneous group of sialic acid storage disorders. Using radiolabeled sialic acid (NeuAc) as a substrate, we have recently detected and characterized a proton-driven carrier for sialic acid in the lysosomal membrane from rat liver. This carrier also recognizes and transports other acidic monosaccharides, among which are uronic acids. If no alternative routes of glucuronic acid transport exist, the disposal of uronic acids can be affected in the sialic acid storage disorders. In this study we excluded the existence of more than one acidic monosaccharide carrier by measuring uptake kinetics of labeled glucuronic acid [( 3H]GlcAc) in rat lysosomal membrane vesicles. [3H]GlcAc uptake was carrier-mediated with an affinity constant of transport (Kt) of 0.3 mM and the transport could be cis-inhibited or trans-stimulated to the same extent by sialic acid or glucuronic acid. Human lysosomal membrane vesicles isolated from cultured fibroblasts showed the existence of a similar proton-driven transporter with the same properties as the rat liver system (Kt of [3H]GlcAc uptake 0.28 mM). Uptake studies with [3H]NeuAc and [3H]GlcAc in resealed lysosome membrane vesicles from cultured fibroblasts of patients with different clinical presentation of sialic acid storage showed defective carrier-mediated transport for both sugars. Further evidence that the defective transport of acidic sugars represents the primary genetic defect in sialic acid storage diseases was provided by the observation of reduced, half-normal transport rates in lymphoblast-derived lysosomal membrane vesicles from five unrelated obligate heterozygotes. This study reports the first observation of a human lysosomal transport defect for multiple physiological compounds.


Temporal-frequency tuning of direction selectivity in cat visual cortex.
Responses of 71 cells in areas 17 and 18 of the cat visual cortex were recorded extracellularly while stimulating with gratings drifting in each direction across the receptive field at a series of temporal frequencies. Direction selectivity was most prominent at temporal frequencies of 1-2 Hz. In about 20% of the total population, the response in the nonpreferred direction increased at temporal frequencies of around 4 Hz and direction selectivity was diminished or lost. In a few cells the preferred direction reversed. One consequence of this behavior was a tendency for the preferred direction to have lower optimal temporal frequencies than the nonpreferred direction. Across the population, the preferred direction was tuned almost an octave lower. In spite of this, temporal resolution was similar in the two directions. It appeared that responses in the nonpreferred direction were suppressed at low frequencies, then recovered at higher frequencies. This phenomenon might reflect the convergence in visual cortex of lagged and nonlagged inputs from the lateral geniculate nucleus. These afferents fire about a quarter-cycle apart (i.e. are in temporal quadrature) at low temporal frequencies, but their phase difference increases to a half-cycle by about 4 Hz. Such timing differences could underlie the prevalence of direction-selective cortical responses at 1 and 2 Hz and the loss of direction selectivity in many cells by 4 or 8 Hz.


Lessons from the trenches: meeting evaluation challenges in school health education.
Those involved in school health education programs generally believe that health-education programs can play an important role in helping young people make positive health decisions. Thus, it is to document the effects of such programs through rigorous evaluations published in peer-reviewed journals. This paper helps the reader understand the context of school health program evaluation, examines several problems and challenges, shows how problems can often be fixed, or prevented, and demonstrates ways in which challenges can be met. A number of topics are addressed, including distinguishing between curricula evaluation and evaluation of outcomes, types of evaluation, identifying stakeholders in school health evaluation, selection of a program evaluator, recruiting participants, design issues, staff training, parental consent, instrumentation, program implementation and treatment fidelity, participant retention, data collection, data analysis and interpretation, presentation of results, and manuscript preparation and submission. Although there is a lack of health-education program evaluation, rigorous evaluations that have been conducted have, at least in some cases, led to wider dissemination of effective programs. These suggestions will help those interested in school health education understand the importance of evaluation and will provide important guidelines for those conducting evaluations of school health-education programs.


Impaired cerebral blood flow regulation in chronic traumatic brain injury.
Baroreflex sensitivity (BRS) and cerebral autoregulation (CA) play an important role in maintaining constant cerebral blood flow (CBF) during systemic changes in blood pressure (BP). Impaired BRS and CA have been reported in acute traumatic brain injury (TBI) which may also contribute to secondary injury and poorer recovery after acute TBI; however, their status during chronic stages remains elusive. Thus, the goal of this study is to determine whether cardiac BRS and dynamic CA (dCA) were impaired during the chronic stage in patients with single TBI and persistent neurological symptoms. Twenty-two subjects with blunt head TBI ≥ 6 months prior to the study (13 mild and 9 moderate to severe TBI) and persistent symptoms on Rivermead Post-Concussion Symptoms Questionnaire at enrollment were compared to 22 age/sex/fitness level-matched healthy control subjects. Beat-to-beat changes in heart rate, BP, and CBF velocity were measured at rest and during a repeated sit-stand maneuver. Hemodynamic variability, dCA, and cardiac BRS were calculated using spectral and transfer function analyses. We found dCA phase in low frequency (LF) range of 0.07-0.20 Hz was lower in subjects with TBI than in control subjects (0.51 ± 0.19 vs. 0.63 ± 0.26, p = 0.043) during the resting condition. Among subjects with TBI, the lower dCA phase in LF was correlated with poorer performance on measures of cognitive function (all p < 0.05). These findings suggested that subjects with chronic TBI showed impaired dCA which may contribute to persistent cognitive impairment. Cerebrovascular measures may provide a physiological measure to evaluate interventions for chronic TBI and accompanying functional deficits.


The stumptailed macaque as a model for baldness: effects of minoxidil.
Synopsis Topical application of minoxidil in bald scalps of stumptailed macaques successfully induced regrowth of terminal hairs. The rate and degree of hair growth by minoxidil are much greater in the early stage of baldness in adolescent and young adults. Minoxidil also prevented the development of baldness when applied on non-bald scalps of peri-adolescent animals. Morphometric analysis of hair follicles (folliculograms) has brought a new aspect in observing cyclic dynamics and growth (transformation) of hair follicles. Using this analytic method and autoradiographic observation of DNA synthesis of hair follicles, the action of minoxidil appears to be a potent mitotic stimulator of the follicular as well as peri-follicular germinal (or reserve) cells, thus inducing an enlargement of vellus follicles through the process of cyclic growth and maintaining anagen follicles in the growing phases. Most importantly, minoxidil has no influence in epidermal keratinocytes, sebaceous glands and other dermal components. During almost 3 years of consecutive treatment, the animals showed no detectable local or systemic side effects when examined by laboratory tests of blood cells, chemistry, steroid hormones, measurement of blood pressure and EKG test.


Hydrophobicity of Bacillus and Clostridium spores.
The hydrophobicities of spores and vegetative cells of several species of the genera Bacillus and Clostridium were measured by using the bacterial adherence to hexadecane assay and hydrophobic interaction chromatography. Although spore hydrophobicity varied among species and strains, the spores of each organism were more hydrophobic than the vegetative cells. The relative hydrophobicities determined by the two methods generally agreed. Sporulation media and conditions appeared to have little effect on spore hydrophobicity. However, exposure of spore suspensions to heat treatment caused a considerable increase in spore hydrophobicity. The hydrophobic nature of Bacillus and Clostridium spores suggests that hydrophobic interactions may play a role in the adhesion of these spores to surfaces.


Comparative effectiveness of surgical versus nonoperative management of unilateral, nondisplaced, subaxial cervical spine facet fractures without evidence of spinal cord injury: clinical article.
Facet joints are major stabilizers of cervical motion allowing for effortless and pain-free multidimensional cervical spine movements without significant linear or rotational translation, thus minimizing any chance for spinal cord or nerve root impingement. Unilateral, nondisplaced subaxial facet fractures do not meet the conventional criteria for spinal instability under physiological loads. Limited evidence indicates that even with no or minimal displacement, 20%-80% of these fractures fail nonoperative management. The risk factors for instability in isolated nondisplaced subaxial facet fractures remain uncertain. In this retrospective study of prospectively collected data, the authors attempted to identify the predictors of failure in the management of isolated, nondisplaced subaxial facet fractures admitted to their Level I trauma center over a 10-year period. Demographic, clinical, imaging, and follow-up data for 25 patients with unilateral nondisplaced subaxial facet fractures who were managed surgically (n = 10) or nonoperatively (n = 15) were statistically analyzed. The mean age of the patients was 38 years, 19 were male, and 21 of the fractures were the result of either motor vehicle accidents or falls. The mean motor score on the American Spinal Injury Association scale was 99.2, and the mean Subaxial Injury Classification (SLIC) severity score was 3 (operated 3.5, nonoperated 2.3). Allen mechanistic classification included 22 compressive-extension Stage 1 and 2 distractive-extension Stage 1 fractures. Subaxial facet fractures involved C-7 in 17 patients (68%), C-6 in 7 (28%), and C-3 in 1 (4%). The anatomical plane of fracture through the lateral mass was sagittal in 12 patients, axial in 8, and coronal in 3 patients. Nondisplaced floating lateral mass injuries were noted in 2 patients. The mean instability score, considering 7 components of the discoligamentous complex on MRI, was 3.2 (operated 3.6, nonoperated 3.0). Ten (40%) of 25 patients in this investigation did not have successful management, 9 in the nonoperated and 1 in the operated group (p = 0.018). Unsuccessful management was significantly greater in younger patients (p = 0.0008), possibly indicating selection bias (p = 0.07, Wilcoxon ranksum test). Fracture plane, instability, and SLIC scores did not play a significant role in treatment failure in this study. In this study, surgery was superior to nonoperative management of isolated, nondisplaced, or minimally displaced subaxial cervical spine facet fractures.


1,2-diacetylbenzene, the neurotoxic metabolite of a chromogenic aromatic solvent, induces proximal axonopathy.
Several widely used aromatic hydrocarbon solvents reportedly induce blue-green discoloration of tissues and urine in animals and humans. The chomophore has been proposed to result from a ninhydrin-like reaction with amino groups in proteins. The present study examines the neurotoxic property of 1,2-diacetylbenzene (1,2-DAB), the active metabolite of the chromogenic and neurotoxic aromatic solvent 1,2-diethylbenzene. Rats treated with 1,2-DAB, but not with the nonchromogenic isomer 1,3-DAB or with ninhydrin developed blue discoloration of internal organs, including the brain and spinal cord. Only 1,2-DAB induced limb weakness associated with nerve fiber changes, which were most prominent in spinal cord and spinal roots. Changes began with the formation of proximal, neurofilament-filled axonal swellings of the type seen after treatment with 3,4-dimethyl-2,5-hexanedione, a potent derivative of the active metabolite of the neurotoxic aliphatic hydrocarbon solvents n-hexane and methyl n-butyl ketone. These compounds are metabolized to a gamma-diketone that forms pyrroles with target proteins, such as neurofilament proteins. A comparable mechanism is considered for 1,2-DAB, an aromatic gamma-diketone.


Complete chloroplast genome sequence of Fritillaria unibracteata var. wabuensis based on SMRT Sequencing Technology.
Fritillaria unibracteata var. wabuensis is an important medicinal plant used for the treatment of cough symptoms related to the respiratory system. The chloroplast genome of F. unibracteata var. wabuensis (GenBank accession no. KF769142) was assembled using the PacBio RS platform (Pacific Biosciences, Beverly, MA) as a circle sequence with 151 009 bp. The assembled genome contains 133 genes, including 88 protein-coding, 37 tRNA, and eight rRNA genes. This genome sequence will provide important resource for further studies on the evolution of Fritillaria genus and molecular identification of Fritillaria herbs and their adulterants. This work suggests that PacBio RS is a powerful tool to sequence and assemble chloroplast genomes.


Predicting the clinical course of suspected acute viral upper respiratory tract infection in children.
Suspected acute viral upper respiratory tract infection (SAVURTI) is the commonest acute reason why children consult in general practice. The clinical course varies widely and about one in five children re-consult for the same SAVURTI episode. If clinicians had feasible tools for predicting which children are likely to suffer a prolonged course, then additional explanations and possibly treatments could be provided at the initial consultation that might enable carers to manage the condition without re-consulting. To identify features available on the day of consulting that might predict a prolonged clinical course among children with SAVURTI. Regression analysis using Canadian Respiratory Illness and Flu Scale (CARIFS) data from a randomized controlled trial cohort of children aged from 6 months to 12 years consulting in general practice with SAVURTI. Two variables from the clinician's records ('age' and 'cough') and two variables from the CARIFS completed by carers on the day of consulting ('fever' and 'low energy, tired') explained approximately 15% of the variation present in CARIFS scores on day seven. Children and carers may benefit from a clear account of the evidence that the clinical course of RTIs in children varies widely and may be longer that expected, and that prediction for individuals is difficult.


Impact of the 2008 economic and financial crisis on child health: a systematic review.
The aim of this study was to provide an overview of studies in which the impact of the 2008 economic crisis on child health was reported. Structured searches of PubMed, and ISI Web of Knowledge, were conducted. Quantitative and qualitative studies reporting health outcomes on children, published since 2007 and related to the 2008 economic crisis were included. Two reviewers independently assessed studies for inclusion. Data were synthesised as a narrative review. Five hundred and six titles and abstracts were reviewed, from which 22 studies were included. The risk of bias for quantitative studies was mixed while qualitative studies showed low risk of bias. An excess of 28,000-50,000 infant deaths in 2009 was estimated in sub-Saharan African countries, and increased infant mortality in Greece was reported. Increased price of foods was related to worsening nutrition habits in disadvantaged families worldwide. An increase in violence against children was reported in the U.S., and inequalities in health-related quality of life appeared in some countries. Most studies suggest that the economic crisis has harmed children's health, and disproportionately affected the most vulnerable groups. There is an urgent need for further studies to monitor the child health effects of the global recession and to inform appropriate public policy responses.


Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis.
To investigate the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors, compared to a standard RA population. Patients were recruited from a regional register, which includes over 90% of patients with RA started on TNF blockers in 1999 or later, and a local community based cohort of RA patients, established in 1997. Of a total of 983 patients in the combined cohort, 531 received treatment with etanercept or infliximab during the study period. The total cohort (n = 983) was linked with national registers for inpatient care and cause of death through December 31, 2001. CVD was defined as the first inpatient care or death from CVD without inpatient care for CVD prior to study entry. First CVD events in those treated versus not treated with TNF blockers were estimated, using age and sex adjusted incidence density computations with treatment and disease severity markers as time-dependent covariates. In the anti-TNF-treated patients, the age-sex adjusted incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7-22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46 (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated. These findings suggest that the risk of developing CVD is lower in patients with RA treated with TNF blockers. This is compatible with the hypothesis that inflammation contributes to the development of cardiovascular events.


Idarubicin in patients with diffuse large cell lymphomas: a randomized trial comparing VACOP-B (A = doxorubicin) vs VICOP-B (I = idarubicin).
Idarubicin is an effective drug in acute leukemia but its use in non-Hodgkin lymphomas (NHLs) is not yet well established. We evaluated its efficacy in patients with diffuse large cell lymphoma (DLCL) by means of a randomized trial comparing two 12-week regimens (VACOP-B and VICOP-B) which differed only in the anthracycline drug used (doxorubicin vs idarubicin). From January 1992 to December 1994, 104 patients aged less than 65 years with de novo advanced stage DLCL were enrolled. Fifty-two patients were treated with VACOP-B (doxorubicin 50 mg/sqm) and 52 with VICOP-B (idarubicin initially 8 mg/sqm and thereafter 10 mg/sqm). Clinical characteristics of the two groups were not significantly different. One HBsAg+ patient died of hepatic necrosis in the VICOP-B arm, and severe (WHO grade > 2) toxicities occurred in 7 patients treated with VACOP-B and in 5 treated with VICOP-B; the only significant difference was for mucositis (p = 0.02). Complete remission (CR) was obtained in 79% of patients receiving VACOP-B and in 56% (idarubicin 8 mg/sqm) and 75% (idarubicin 10 mg/sqm) of those in the VICOP-B group (p = n.s.). Prognostic factors that negatively affected CR were advanced stage in VACOP, bone marrow infiltration in both schedules. At a median follow-up of two years, overall survival (67% VACOP and 61% VICOP) and disease-free survival (65% and 67%, respectively) were not significantly different. Idarubicin is slightly less toxic than doxorubicin; at a dose of 10 mg/sqm the former is easily tolerated and shows the same efficacy as doxorubicin in the treatment of DLCL.


Toxicokinetic variation in 15 freshwater arthropod species exposed to the insecticide chlorpyrifos.
Recent advances in modeling the processes of the toxicity of chemicals-toxicokinetics (TK) and toxicodynamics (TD)-are improving environmental risk assessment (ERA) through prediction of effects from time-varying exposure. This has been achieved by linking chemical fate and toxicological effects mechanistically, based on internal concentrations, through the tissue residue approach. However, certain questions remain: for example, how do TK and TD differ among species and how does this relate to differences in species sensitivity? In a series of experiments, we studied the TK of [(14)C]chlorpyrifos in 15 freshwater arthropod species, two of which were studied in juvenile and adult life stages. Uptake (k(in)) and elimination (k(out)) rate constants were fitted using a one-compartment single first-order kinetic model. The application of two complementary parameter estimation methods facilitated the calculation of bioconcentration factors (BCF) with prediction intervals and 95% depuration times (t(95)) for all tested species. Extremely slow elimination was observed in some species as well as high overall variation in k(in), k(out), BCF, and t(95) across the tested aquatic arthropod species. This variation has implications for the development of TKTD approaches in ERA, including assessing fluctuating exposure concentrations and the interpretation of observed toxicity responses in the laboratory and in the field.


Practical guidelines for online Narrative Exposure Therapy (e-NET) - a short-term treatment for posttraumatic stress disorder adapted for remote delivery.
Background: Online therapy has become increasingly desirable and available in recent years, with the current COVID-19 pandemic acting as a catalyst to develop further protocols enabling therapists to conduct online treatment safely and efficaciously. Offering online treatment potentially means that treatments are available to clients who would otherwise have no access, closing the gap in the provision of mental health services worldwide. Objective: This paper focuses on practical guidelines using online Narrative Exposure Therapy (e-NET). It aims to be an addition to the general manual of NET to enable therapists to deliver online treatment. The face-to-face version of NET is a well-known short-term and evidence-based treatment for posttraumatic stress disorder; e-NET is currently being tested in several additional trials. Methods: The differences between NET and e-NET are elaborated and depicted in detail. Results: Difficulties encountered in e-NET delivery, e.g. confidentiality, dealing with interruptions, comorbid symptoms among others, are similar to those that occur during face to face interventions but the solutions have to be adapted. Dissociation is often regarded as a challenge in face-to-face treatment, and requires particular attention within the online setting. Therefore, tools for addressing dissociation in this particular setting are presented. Conclusions: These practical guidelines show the advantages as well as the challenges therapists face when conducting e-NET. They aim to empower therapists working with trauma clients to conduct e-NET confidently and safely.


Children who read words accurately despite language impairment: who are they and how do they do it?
Some children learn to read accurately despite language impairments (LI). Nine- to 10-year-olds were categorized as having LI only (n = 35), dyslexia (DX) only (n = 73), LI + DX (n = 54), or as typically developing (TD; n = 176). The LI-only group had mild to moderate deficits in reading comprehension. They were similar to the LI + DX group on most language measures, but rapid serial naming was superior to the LI + DX group and comparable to the TD. For a subset of children seen at 4 and 6 years, early phonological skills were equally poor in those later classified as LI or LI + DX. Poor language need not hinder acquisition of decoding, so long as rapid serial naming is intact; reading comprehension, however, is constrained by LI.


Fate of the Ophthalmic Artery After Treatment With the Pipeline Embolization Device.
Flow diverters have emerged as a major tool in the treatment of cerebral aneurysms. A crucial issue with the use of flow diverters is the patency of side branches covered by the device, most importantly the ophthalmic artery (OA). To assess the patency of the OA after coverage with the pipeline embolization device (PED). All patients who had a PED covering the OA and in whom angiographic follow-up was available were included in the study. The patency of the OA at follow-up was systematically evaluated by 2 authors who were not involved in the procedure. Of 95 treated patients, the OA was covered by 1 PED in 81 patients (85%) and by 2 PEDs in 14 patients (15%). Mean angiographic follow-up was 7.5 months, ranging from 3 to 24 months. At the latest follow-up, the OA remained patent in 85 patients (89%), showed diminished flow in 4 patients (4%), and was occluded in 6 patients (7%). Only 1 patient had clinical symptoms related to OA occlusion. In multivariable analysis, larger aneurysm size predicted OA occlusion (P = .04). There was also a strong trend for younger age (P = .06) and coverage by more than 1 device (P = .07). Treatment of internal carotid artery aneurysms with the PED preserves the patency of the OA in most cases. The occlusion of the OA in the few cases where it occurs is usually a clinically irrelevant event. Minimizing the number of PEDs across the OA is crucial to preserve its patency.


Multidisciplinary approach in diagnosis of lung carcinoma.
To employ multidisciplinary approach in order to make the correct diagnosis of lung carcinoma clinically and morphologically mimicking lymphoma. Immunostaining was performed by incubating tissue sections with appropriate antibodies, using the streptavidin-biotin technique. Antigen-antibody complexes were visualized with 3-amino-9-ethylcarbasole or diaminobenzidine hydrochloride substrate solution. We have investigated p53 gene mutations by polymerase chain reaction and DNA sequence analysis of exons 5, 6, 7, 8 and 9. Tumor cells expressed cytokeratin AE1/AE3, epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF-1) without thyreoglobulin positivity. Further, tumor cells expressed neuroendocrine mar kers: synaptophysin, chromogranin A, neuron-specific enolase (NSE), CD56/NCAM, CD57/Leu-7 and protein gene product 9.5 (PGP9.5). P53 was also expressed. Diffuse large cell lymphomas of B and T cell origin were excluded. Direct sequencing analysis of exon 6 of the p53 gene revealed ATC to ACC mutation at codon 195. Final diagnosis of large cell lung neuroendocrine carcinoma (LCNEC) was established. Morphological pattern of tumor complied with large cell non-Hodgkin's lymphoma, but large cell lung carcinoma with neuroendocrine differentiation was proved immunohistochemically and confirmed by genetic analysis of p53 mutations in tumor tissue sample. Multidisciplinary approach in diagnosis of lung carcinoma is useful for its final diagnosis.


UV-A1 therapy for nephrogenic systemic fibrosis.
Nephrogenic systemic fibrosis (NSF) is a rare sclerosing skin condition associated with end-stage renal disease and gadolinium exposure. Therapy for NSF is challenging, with few options other than preventing exposure to gadolinium and improving renal function through transplant. However, in some cases neither of these options is tenable. We report the successful use of UV-A1 phototherapy in 4 patients with NSF. Four patients with NSF were treated with UV-A1 phototherapy at a tertiary medical center from 2005 through 2007. To our knowledge, it is unique to this series that all patients were receiving hemodialysis before, during, and after therapy with UV-A1. All experienced improvement in the degree of induration, and 2 experienced improvement in mobility of the hands and legs. Total treatments ranged from 22 treatments (with a cumulative dose of 1855 J/cm(2)) to 50 treatments (total UV-A1 exposure, 3850 J/cm(2)). No adverse events were observed. Although no patient had complete resolution of indurated plaques, the improvement was substantial. For 2 patients, it resulted in a resumption of hand and leg mobility. As a result, UV-A1 therapy may represent a treatment for NSF when kidney transplantation is not an option or is delayed. Limitations of this study include the lack of a controlled trial, lack of quantification of gadolinium levels within tissue, and the lack of a defined grading scale for NSF severity.


Dynamic pH-induced conformational changes of the PsbO protein in the fluctuating acidity of the thylakoid lumen.
The PsbO protein is an essential extrinsic subunit of photosystem II, the pigment-protein complex responsible for light-driven water splitting. Water oxidation in photosystem II supplies electrons to the photosynthetic electron transfer chain and is accompanied by proton release and oxygen evolution. While the electron transfer steps in this process are well defined and characterized, the driving forces acting on the liberated protons, their dynamics and their destiny are all largely unknown. It was suggested that PsbO undergoes proton-induced conformational changes and forms hydrogen bond networks that ensure prompt proton removal from the catalytic site of water oxidation, i.e. the Mn4 CaO5 cluster. This work reports the purification and characterization of heterologously expressed PsbO from green algae Chlamydomonas reinhardtii and two isoforms from the higher plant Solanum tuberosum (PsbO1 and PsbO2). A comparison to the spinach PsbO reveals striking similarities in intrinsic protein fluorescence and CD spectra, reflecting the near-identical secondary structure of the proteins from algae and higher plants. Titration experiments using the hydrophobic fluorescence probe ANS revealed that eukaryotic PsbO proteins exhibit acid-base hysteresis. This hysteresis is a dynamic effect accompanied by changes in the accessibility of the protein's hydrophobic core and is not due to reversible oligomerization or unfolding of the PsbO protein. These results confirm the hypothesis that pH-dependent dynamic behavior at physiological pH ranges is a common feature of PsbO proteins and causes reversible opening and closing of their β-barrel domain in response to the fluctuating acidity of the thylakoid lumen.


Preservation of organic matter in sediments promoted by iron.
The biogeochemical cycles of iron and organic carbon are strongly interlinked. In oceanic waters, organic ligands have been shown to control the concentration of dissolved iron. In soils, solid iron phases shelter and preserve organic carbon, but the role of iron in the preservation of organic matter in sediments has not been clearly established. Here we use an iron reduction method previously applied to soils to determine the amount of organic carbon associated with reactive iron phases in sediments of various mineralogies collected from a wide range of depositional environments. Our findings suggest that 21.5 ± 8.6 per cent of the organic carbon in sediments is directly bound to reactive iron phases. We further estimate that a global mass of (19-45) × 10(15) grams of organic carbon is preserved in surface marine sediments as a result of its association with iron. We propose that these associations between organic carbon and iron, which are formed primarily through co-precipitation and/or direct chelation, promote the preservation of organic carbon in sediments. Because reactive iron phases are metastable over geological timescales, we suggest that they serve as an efficient 'rusty sink' for organic carbon, acting as a key factor in the long-term storage of organic carbon and thus contributing to the global cycles of carbon, oxygen and sulphur.