A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology.
Understanding variations in the incidence of schizophrenia is a crucial step in unravelling the aetiology of this group of disorders. The aims of this review are to systematically identify studies related to the incidence of schizophrenia, to describe the key features of these studies, and to explore the distribution of rates derived from these studies. Studies with original data related to the incidence of schizophrenia (published 1965-2001) were identified via searching electronic databases, reviewing citations and writing to authors. These studies were divided into core studies, migrant studies, cohort studies and studies based on Other Special Groups. Between- and within-study filters were applied in order to identify discrete rates. Cumulative plots of these rates were made and these distributions were compared when the underlying rates were sorted according to sex, urbanicity, migrant status and various methodological features. We identified 100 core studies, 24 migrant studies, 23 cohort studies and 14 studies based on Other Special Groups. These studies, which were drawn from 33 countries, generated a total of 1,458 rates. Based on discrete core data for persons (55 studies and 170 rates), the distribution of rates was asymmetric and had a median value (10%-90% quantile) of 15.2 (7.7-43.0) per 100,000. The distribution of rates was significantly higher in males compared to females; the male/female rate ratio median (10%-90% quantile) was 1.40 (0.9-2.4). Those studies conducted in urban versus mixed urban-rural catchment areas generated significantly higher rate distributions. The distribution of rates in migrants was significantly higher compared to native-born; the migrant/native-born rate ratio median (10%-90% quantile) was 4.6 (1.0-12.8). Apart from the finding that older studies reported higher rates, other study features were not associated with significantly different rate distributions (e.g. overall quality, methods related to case finding, diagnostic confirmation and criteria, the use of age-standardization and age range). There is a wealth of data available on the incidence of schizophrenia. The width and skew of the rate distribution, and the significant impact of sex, urbanicity and migrant status on these distributions, indicate substantial variations in the incidence of schizophrenia.


Extradural spinal cord lesion in a dog: first case study of canine neurological histoplasmosis in Italy.
A 7-year-old intact male mixed dog was presented with a history of acute and progressive paraparesis. Abnormal clinical signs consisted of non-ambulatory paraparesis, hind limbs hypertonia and severe thoracolumbar pain. Magnetic resonance imaging demonstrated an isointense in T1 and T2 WI epidural lesion, with good contrast enhancement, extending from T-10 to T-13. Laminectomy was carried out to remove the epidural mass. Histological examination revealed a pyogranulomatous lesion characterized by numerous macrophages containing yeast-like Grocott and PAS-positive bodies. Immunohistochemistry and PCR performed on formalin-fixed paraffin-embedded tissue confirmed Histoplasma capsulatum as the causative agent. H. capsulatum has a worldwide distribution in temperate and subtropical climates but its presence as an autochthonous fungus in Europe is now recognized. To the authors' knowledge this is the first report of canine histoplasmosis in Italy with lesion confined to the central nervous system.


A life history approach to delineating how harsh environments and hawk temperament traits differentially shape children's problem-solving skills.
Harsh environments are known to predict deficits in children's cognitive abilities. Life history theory approaches challenge this interpretation, proposing stressed children's cognition becomes specialized to solve problems in fitness-enhancing ways. The goal of this study was to examine associations between early environmental harshness and children's problem-solving outcomes across tasks varying in ecological relevance. In addition, we utilize an evolutionary model of temperament toward further specifying whether hawk temperament traits moderate these associations. Two hundred and one mother-child dyads participated in a prospective multimethod study when children were 2 and 4 years old. At age 2, environmental harshness was assessed via maternal report of earned income and observations of maternal disengagement during a parent-child interaction task. Children's hawk temperament traits were assessed from a series of unfamiliar episodes. At age 4, children's reward-oriented and visual problem-solving were measured. Path analyses revealed early environmental harshness and children's hawk temperament traits predicted worse visual problem-solving. Results showed a significant two-way interaction between children's hawk temperament traits and environmental harshness on reward-oriented problem-solving. Simple slope analyses revealed the effect of environmental harshness on reward-oriented problem-solving was specific to children with higher levels of hawk traits. Results suggest early experiences of environmental harshness and child hawk temperament traits shape children's trajectories of problem-solving in an environment-fitting manner.


Experimental study on polarization lens formed by asymmetrical metallic hole array.
A polarization bifocal lens based on the polarization effect caused by asymmetrical hole arrays had been designed, fabricated, and characterized experimentally. By considering the fact that the skin depth of an infrared electromagnetic field inside metal is much shorter than the incident wavelength, a polarization bifocal lens composed of high deep-width ratio metallic holes was realized by using a gold-coated silicon structure to replace the one directly formed on a thick metal film. An infrared optical experiment setup is built based on the secondary imagery method for characterizing the focal length of the designed bifocal lens. The measured focal lengths of the fabricated bifocal lens coincide well with the designed values, which proves the validity for realizing the polarization elements with the proposed structure and the feasibility of the fabrication process.


Impact of baroreflex activation therapy on renal function--a pilot study.
Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients. 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables. The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients. The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR.


Gait variability and motor control in people with knee osteoarthritis.
Knee osteoarthritis (OA) is a common disease that impairs walking ability and function. We compared the temporal gait variability and motor control in people with knee OA with healthy controls. The purpose was to test the hypothesis that the temporal gait variability would reflect a more stereotypic pattern in people with knee OA compared with healthy age-matched subjects. To assess the gait variability the temporal structure of the ankle and knee joint kinematics was quantified by the largest Lyapunov exponent and the stride time fluctuations were quantified by sample entropy and detrended fluctuation analysis. The motor control was assessed by the soleus (SO) Hoffmann (H)-reflex modulation and muscle co-activation during walking. The results showed no statistically significant mean group differences in any of the gait variability measures or muscle co-activation levels. The SO H-reflex amplitude was significantly higher in the knee OA group around heel strike when compared with the controls. The mean group difference in the H-reflex in the initial part of the stance phase (control-knee OA) was -6.6% Mmax (95% CI: -10.4 to -2.7, p=0.041). The present OA group reported relatively small impact of their disease. These results suggest that the OA group in general sustained a normal gait pattern with natural variability but with suggestions of facilitated SO H-reflex in the swing to stance phase transition. We speculate that the difference in SO H-reflex modulation reflects that the OA group increased the excitability of the soleus stretch reflex as a preparatory mechanism to avoid sudden collapse of the knee joint which is not uncommon in knee OA.


H7N9 influenza A virus in turkeys in Minnesota.
Introductions of H7 influenza A virus (IAV) from wild birds into poultry have been documented worldwide, resulting in varying degrees of morbidity and mortality. H7 IAV infection in domestic poultry has served as a source of human infection and disease. We report the detection of H7N9 subtype IAVs in Minnesota (MN) turkey farms during 2009 and 2011. The full genome was sequenced from eight isolates as well as the haemagglutinin (HA) and neuraminidase (NA) gene segments of H7 and N9 virus subtypes for 108 isolates from North American wild birds between 1986 and 2012. Through maximum-likelihood and coalescent phylogenetic analyses, we identified the recent H7 and N9 IAV ancestors of the turkey-origin H7N9 IAVs, estimated the time and geographical origin of the ancestral viruses, and determined the relatedness between the 2009 and 2011 turkey-origin H7N9 IAVs. Analyses supported that the 2009 and 2011 viruses were distantly related genetically, suggesting that the two outbreaks arose from independent introduction events from wild birds. Our findings further supported that the 2011 MN turkey-origin H7N9 virus was closely related to H7N9 IAVs isolated in poultry in Nebraska during the same year. Although the precise origin of the wild-bird donor of the turkey-origin H7N9 IAVs could not be determined, our findings suggested that, for both the NA and HA gene segments, the MN turkey-origin H7N9 viruses were related to viruses circulating in wild birds between 2006 and 2011 in the Mississippi Flyway.


Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?
Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (β = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (β coefficient = 5.89, P = .03). Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.


Detection of Inter-Lineage Natural Recombination in Avian Paramyxovirus Serotype 1 Using Simplified Deep Sequencing Platform.
Newcastle disease virus (NDV) is a prototype member of avian paramyxovirus serotype 1 (APMV-1), which causes severe and contagious disease in the commercial poultry and wild birds. Despite extensive vaccination programs and other control measures, the disease remains endemic around the globe especially in Asia, Africa, and the Middle East. Being a single serotype, genotype II based vaccines remained most acceptable means of immunization. However, the evidence is emerging on failures of vaccines mainly due to evolving nature of the virus and higher genetic gaps between vaccine and field strains of APMV-1. Most of the epidemiological and genetic characterizations of APMVs are based on conventional methods, which are prone to mask the diverse population of viruses in complex samples. In this study, we report the application of a simple, robust, and less resource-demanding methodology for the whole genome sequencing of NDV, using next-generation sequencing (NGS) on the Illumina MiSeq platform. Using this platform, we sequenced full genomes of five virulent Malaysian NDV strains collected during 2004-2013. All isolates clustered within highly prevalent lineage 5 (specifically in lineage 5a); however, a significantly greater genetic divergence was observed in isolates collected from 2004 to 2011. Interestingly, genetic characterization of one isolate collected in 2013 (IBS025/13) shown natural recombination between lineage 2 and lineage 5. In the event of recombination, the isolate (IBS025/13) carried nucleocapsid protein consist of 55-1801 nucleotides (nts) and near-complete phosphoprotein (1804-3254 nts) genes of lineage 2 whereas surface glycoproteins (fusion, hemagglutinin-neuraminidase) and large polymerase of lineage 5. Additionally, the recombinant virus has a genome size of 15,186 nts which is characteristics for the old genotypes I-IV isolated from 1930 to 1960. Taken together, we report the occurrence of a natural recombination in circulating strains of NDV in commercial poultry using NGS methodology. These findings will not only highlight the potential of RNA viruses to evolve but also to consider the application of NGS in revealing the genetic diversity of these viruses in clinical materials. Factors that drive these evolutionary events and subsequent impact of these divergences on clinical outcome of the disease warrant future investigations.


Spatiotemporal activity of the mshA gene system in Shewanella oneidensis MR-1 biofilms.
Type IV pili and a putative EPS biosynthetic gene cluster (mxdABCD) have been implicated previously in biofilm formation in Shewanella oneidensis MR-1. Here, we report that the mannose-sensitive hemagglutinin (MSHA) pilus mediates a reversible, d-mannose-sensitive association of cells to the substratum surface or to other cells that is critical within the first 5 microm of the biofilm from the substratum. The presence of the MSHA pilus alone is insufficient to confer biofilm-forming capacity; its activity, as mediated by the putative pilus retraction motor protein, PilT, is also required. Deletion of pilD, encoding the type IV pili prepilin peptidase, revealed that additional PilD substrate(s) may be involved in biofilm formation beyond the major structural pilin of the MSHA pilus. We also present data showing that the MSHA pilus and mxd genes encode for a complementary set of molecular machineries that constitute the dominant mechanisms enabling biofilm formation in this microorganism under hydrodynamic conditions.


Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats.
To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats. 8 adult cats. On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, i.v.) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 microg/kg/ min, i.v.) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (> or = 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II). In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 microg of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 microg of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 microg/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes. Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 microg/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.


Intelligent driving intelligence test for autonomous vehicles with naturalistic and adversarial environment.
Driving intelligence tests are critical to the development and deployment of autonomous vehicles. The prevailing approach tests autonomous vehicles in life-like simulations of the naturalistic driving environment. However, due to the high dimensionality of the environment and the rareness of safety-critical events, hundreds of millions of miles would be required to demonstrate the safety performance of autonomous vehicles, which is severely inefficient. We discover that sparse but adversarial adjustments to the naturalistic driving environment, resulting in the naturalistic and adversarial driving environment, can significantly reduce the required test miles without loss of evaluation unbiasedness. By training the background vehicles to learn when to execute what adversarial maneuver, the proposed environment becomes an intelligent environment for driving intelligence testing. We demonstrate the effectiveness of the proposed environment in a highway-driving simulation. Comparing with the naturalistic driving environment, the proposed environment can accelerate the evaluation process by multiple orders of magnitude.


Phase noise mitigation of QPSK signal utilizing phase-locked multiplexing of signal harmonics and amplitude saturation.
We demonstrate an all-optical phase noise mitigation scheme based on the generation, delay, and coherent summation of higher order signal harmonics. The signal, its third-order harmonic, and their corresponding delayed variant conjugates create a staircase phase-transfer function that quantizes the phase of quadrature-phase-shift-keying (QPSK) signal to mitigate phase noise. The signal and the harmonics are automatically phase-locked multiplexed, avoiding the need for phase-based feedback loop and injection locking to maintain coherency. The residual phase noise converts to amplitude noise in the quantizer stage, which is suppressed by parametric amplification in the saturation regime. Phase noise reduction of ∼40% and OSNR-gain of ∼3 dB at BER 10(-3) are experimentally demonstrated for 20- and 30-Gbaud QPSK input signals.


Outcomes following infant listing for cardiac transplantation: the impact of strategies introduced to counteract limited donor availability.
Survival following cardiac transplantation in infancy has improved substantially. There is a growing shortage of donors, the impact of which may be offset by increase in ABO-incompatible transplants, size-mismatching and mechanical support. The authors reviewed their results and outcomes following infant listing for cardiac transplantation over 22 years. Children <12 months at time of listing for cardiac transplant in 1987-2008 were identified using the departmental cardiopulmonary transplant database. Details were obtained from databases and hospital medical records and subdivided into two eras, 1987-1997 and 1998-2008. In 1987-2008, 49 infants were listed, and 28 (57%) underwent cardiac transplantation (12 in 1987-1997 and 16 in 1998-2008). 15 patients (31%) died on the waiting list, 6 patients were delisted (5 of these because of recovery of cardiac function). There was a decrease in suitable donor offers from a mean of 36 per year in 1996-2000 to 11 per year in 2001-2006 (p=0.008). In 1998-2008, nine listed infants were on mechanical support; there were seven ABO-incompatible transplants, and all transplants were size-mismatched with donors on average 2.7 times heavier than recipients. Waiting times decreased from median 83 to 47 days. Six (21%) of the transplanted patients died, the majority in 1987-1997 and perioperatively. There has been a fall in suitable donors for infant cardiac transplants over time despite increased demand. However, the introduction of size-mismatching, ABO-incompatible transplants and mechanical support has enabled an increase in the number of transplants to be carried out despite this fall in donor numbers. Outcomes following transplantation have improved over time.


Seasonal Fluctuations of Sap-Feeding Insect Species Infected by Xylella fastidiosa in Apulian Olive Groves of Southern Italy.
A study on seasonal abundance of Auchenorrhyncha species and their infectivity by Xylella fastidiosa in the Apulia region of Italy was conducted to identify ideal periods for monitoring and adoption of potential control measures against insect vectors. Adult populations of Auchenorrhyncha species were monitored monthly over a 2-yr period from five olive groves. A total of 15 species were captured, identified, and tested for presence of X. fastidiosa by polymerase chain reaction (PCR). For three species, Philaenus spumarius L., Neophilaenus campestris (Fallèn), and Euscelis lineolatus Brullé, positive reactions to X. fastidiosa were obtained, on average, in 16.3, 15.9 and 18.4% of adult insects, respectively. Philaneous spumarius was the dominant species (39.8% of total Auchenorrhyncha captured) with the highest adult abundance in summer months. Adult P. spumarius and N. campestris were first detected between March and May in both years, and all insects tested during these periods (year 1: n = 42, year 2: n = 132) gave negative reactions to X. fastidiosa by PCR. Similarly, first adults of E. lineolatus that appeared from October to November (year 1: n = 20, year 2: n = 15) tested negative for presence of X. fastidiosa Given the lack of transstadial and transovarial transmission of X. fastidiosa and considering that P. spumarius is univoltine, control measures against nymphal stages of P. spumarius should be investigated as means of population suppression to reduce spread of X. fastidiosa in olive groves.


Referral from vascular surgery to cardiovascular rehabilitation and related outcomes in patients with peripheral arterial disease: the THINKPAD-RELOADED survey.
The utilization of cardiovascular rehabilitation (CR) programmes in patients with Lower Extremity Peripheral Artery Disease (LEPAD) is generally poor, with limited evidence of current policies for referral. The aim of the study was to evaluate, within a cohesive network of CR and vascular surgery facilities with facilitated referral process, the clinical characteristic of LEPAD patients referred to CR and related outcomes, as compared to patients not referred. The present is an observational prospective study of consecutive patients recruited at vascular surgery facilities. Out of 329 patients observed, the average referral rate to CR was 34% (28% and 39% in patients with and without recent peripheral revascularization, p<0.05). LEPAD patients entering the CR programme were similar to those who did not according to sex, age, the vascular surgery setting of evaluation, and localization of arterial lesions. Patients with moderate intermittent claudication and patients with acute limb ischemia as index event were more represented among those who attended CR (41% vs 21% and 9% vs 2% respectively, p<0.05). Patients referred to CR had five times more episodes of acute coronary syndrome and heart failure as complication of the index event. The cardiovascular risk profile (obesity 29.5% vs 11%, p<0.05; hypercholesterolemia 80% vs 61%, p<0.05) was much worse in LEPAD patients referred to CR, but conversely, they better achieved secondary prevention targets, particularly for blood pressure control (97% vs 57%, p<0.05). All-cause 2-year mortality in the whole patients' population was 6%. Patients entering the CR programme displayed less events (13.5% vs 37.7%, p<0.05), mainly death (3.1% vs 11.3%, p<0.05) and limb-related events (4.2% vs 15.2%, p<0.05). The results of our study suggest that when a cohesive network of vascular surgery and CR facilities becomes available, the referral rate to rehabilitation may increase up to one third of eligible patients. Patients with higher comorbidity and cardiovascular risk seem to have priority in the referral process, nevertheless those with peripheral revascularization are still underestimated. Entering CR may ensure better cardiovascular risk profile and cardiovascular prognosis in LEPAD patients, and consequently the systematic adoption of this care model needs to be strongly recommended and facilitated.


Development of Machine-Learning Techniques for Time-of-Flight Secondary Ion Mass Spectrometry Spectral Analysis: Application for the Identification of Silane Coupling Agents in Multicomponent Films.
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is an important analysis technique that can gather vast amounts of information from surfaces. Recently, machine learning was combined with ToF-SIMS to successfully extract useful information from mass spectra. However, the descriptor generation required for ToF-SIMS analysis using machine learning remains challenging because it requires a lot of effort, is time-consuming, and significantly limits the versatility and practicality of the machine learning approach for ToF-SIMS analysis. Herein, we proposed a new approach to avoid the descriptor generation: to regard ToF-SIMS spectra as images and apply the convolutional neural network (CNN) to analyze these spectral images. We applied and assessed this approach for the identification of silane coupling agents in multicomponent films. Furthermore, the CNN showed higher accuracy than descriptor-based approaches, suggesting its usefulness in achieving the automation and standardization of the ToF-SIMS analysis.


NeuroMorph: a toolset for the morphometric analysis and visualization of 3D models derived from electron microscopy image stacks.
Serialelectron microscopy imaging is crucial for exploring the structure of cells and tissues. The development of block face scanning electron microscopy methods and their ability to capture large image stacks, some with near isotropic voxels, is proving particularly useful for the exploration of brain tissue. This has led to the creation of numerous algorithms and software for segmenting out different features from the image stacks. However, there are few tools available to view these results and make detailed morphometric analyses on all, or part, of these 3D models. We have addressed this issue by constructing a collection of software tools, called NeuroMorph, with which users can view the segmentation results, in conjunction with the original image stack, manipulate these objects in 3D, and make measurements of any region. This approach to collecting morphometric data provides a faster means of analysing the geometry of structures, such as dendritic spines and axonal boutons. This bridges the gap that currently exists between rapid reconstruction techniques, offered by computer vision research, and the need to collect measurements of shape and form from segmented structures that is currently done using manual segmentation methods.


Comparison of outcomes between axial radial and axial ulnar carpal injuries.
Axial carpal injuries are rare entities where a traumatic force transmits through the intermetacarpal space, dissociating the carpometacarpal joint and disrupting the distal carpal row in an axial radial or axial ulnar pattern via true axial force or compressive crush mechanism. Differences in outcomes remain unclear with regard to the specific type of axial carpal injury pattern. A retrospective case series identified 37 wrists (in 37 patients) over 25 years who presented to a Level 1 trauma centre, with 20 wrists experiencing an axial radial injury and 17 wrists experiencing an axial ulnar injury. Of all the variables evaluated, only axial radial injuries were identified as predictors of poor outcome as defined by Mayo Wrist scores with univariate analysis demonstrating 6 times increased risk and multivariate analysis demonstrating 15 times increased risk of a poor outcome compared with axial ulnar injuries. This knowledge will provide prognostic information to surgeons managing patients with these severe injuries. IV.


p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy.
We previously reported that supplementation of a cationic liposome with transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy of p53 and PTEN tumor suppressor gene therapy in a mouse xenograft model of human prostate PC-3 carcinoma cells, using a vector consisting of dimyristoyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE)-cholesterol (DC) and Tf. When the volume of the tumors grown subcutaneously in athymic nude mice reached 50-60 mm(3), three intratumoral injections of the following four formulations were performed during week 1 and then during week 3: (1) saline, (2) DC + Tf + pCMVlacZ, (3) DC + Tf + pCMVPTEN, and (4) DC + Tf + pCMVp53 (standard formulation). There was no significant difference in tumor volume and survival between group 1 and group 2 animals. As compared with group 1 controls, group 3 animals had slower tumor growth during the first 3 weeks but thereafter their tumor growth rate was similar to that of the controls. By day 2 posttreatment, group 4 animals had significantly lower tumor volume relative to initial tumor volume as well as controls at the comparable time point. Also, animals treated with p53 survived longer. Treatment with DC, Tf, pCMVp53, DC + pCMVp53, or Tf + pCMVp53 had no effect on tumor volume or survival. Expression of p53 protein and apoptosis were detected in tumors treated with the standard formulation, thus associating p53 protein expression and apoptosis with efficacy. However, p53 protein was expressed in only a fraction of the tumor cells, suggesting a role for bystander effects in the efficacy of p53 gene therapy. We conclude that intratumoral gene delivery by a nonviral vector consisting of a cationic liposome and Tf can achieve efficacious p53 gene therapy of prostate cancer.


Challenges for mapping cyanotoxin patterns from remote sensing of cyanobacteria.
Using satellite imagery to quantify the spatial patterns of cyanobacterial toxins has several challenges. These challenges include the need for surrogate pigments - since cyanotoxins cannot be directly detected by remote sensing, the variability in the relationship between the pigments and cyanotoxins - especially microcystins (MC), and the lack of standardization of the various measurement methods. A dual-model strategy can provide an approach to address these challenges. One model uses either chlorophyll-a (Chl-a) or phycocyanin (PC) collected in situ as a surrogate to estimate the MC concentration. The other uses a remote sensing algorithm to estimate the concentration of the surrogate pigment. Where blooms are mixtures of cyanobacteria and eukaryotic algae, PC should be the preferred surrogate to Chl-a. Where cyanobacteria dominate, Chl-a is a better surrogate than PC for remote sensing. Phycocyanin is less sensitive to detection by optical remote sensing, it is less frequently measured, PC laboratory methods are still not standardized, and PC has greater intracellular variability. Either pigment should not be presumed to have a fixed relationship with MC for any water body. The MC-pigment relationship can be valid over weeks, but have considerable intra- and inter-annual variability due to changes in the amount of MC produced relative to cyanobacterial biomass. To detect pigments by satellite, three classes of algorithms (analytic, semi-analytic, and derivative) have been used. Analytical and semi-analytical algorithms are more sensitive but less robust than derivatives because they depend on accurate atmospheric correction; as a result derivatives are more commonly used. Derivatives can estimate Chl-a concentration, and research suggests they can detect and possibly quantify PC. Derivative algorithms, however, need to be standardized in order to evaluate the reproducibility of parameterizations between lakes. A strategy for producing useful estimates of microcystins from cyanobacterial biomass is described, provided cyanotoxin variability is addressed.


Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps.
We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071-5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid (DCA)] are considered to promote formation of colon adenomas and cancer, we have now attempted to find a relationship between polyp reduction and fecal secondary bile acids after feeding UDCA to these rats. We examined the fecal bile acids in rats with polyps and compared them with fecal bile acids in control rats and also determined the bile acid composition in fecal aqueous phase, which is in direct contact with the colon epithelium and may be physiologically more active. Treatment with azoxymethane did not significantly alter fecal bile acid composition in the rats. Cholic acid feeding resulted in greatly increased proportions of DCA (82% of total bile acids versus 18% in control rats). On the other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in control rats fed UDCA and 3% in rats also treated with azoxymethane). In control rats, 96% of the bile acids were present in the water-insoluble fraction and 4% in the water-soluble fraction. The major insoluble bile acids included DCA and hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids were concentrated in the soluble fraction (37%). When 0.4% UDCA was added to the diet, lithocholic acid increased in the insoluble fraction (40 versus 1%), but the hydrophilic UDCA and muricholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed predominantly in the water-insoluble fraction, whereas the hydrophilic bile acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by countering the toxic effect of DCA and enhancing the possible cytoprotective effects of UDCA and muricholic acids in the water-soluble fraction in the feces of rat.


Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype.
IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy. IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.


Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV".
Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction. The meeting brought together international leaders in the area of neurological complications of HIV-1 infection with special focus on the African population. Research presentations indicated that HAND was highly prevalent and that inflammatory cytokines and immune-activation played important roles in progression of neurocognitive impairment. Furthermore, children on antiretroviral therapy were also at risk for developing neurocognitive impairment. With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S). At the cellular level, a Zambian study showed that clade C infection resulted in reduced brain cell death compared with clade B infection suggesting clade specific variations in mediating brain cell injury. Furthermore, ex vivo Tat protein from clade CRF02_AG, prevalent in West/ Central Africa, exhibited reduced disruption of brain endothelium compared with clade B Tat protein. Discussions shed light on future research directions aimed at understanding biomarkers and disease mechanisms critical for HAND.


Validation study of a Kinect based body imaging system.
Understanding the reliability and precision of the data obtained using three-dimensional body scanners is very important if it is intended to replace the traditional data collection methods. If the collection of anthropometric data with three-dimensional body scanners is a fast and reliable process that produces precise data at a low price, it could be used for numerous applications worldwide. Many studies have addressed data collected by white light and laser based scanners. This study provides a comparative analysis between the anthropometric data collected using a Kinect body imaging system with the data collected using traditional manual methods. Moreover, a comparison is also made between the results obtained in this study and the results of previous studies of different types of body scanners. The Mean Absolute Difference was calculated and all the values were compared to the maximum allowable error defined in ISO 20685. Additionally, an analysis of the significant differences between the two acquisition methods was also applied to a physical mannequin, to understand how the body movement and body stance variation in human participants impacts the results obtained. There are few body measurements that are close to this restricted allowable error. The results were better when the mannequin was measured. Although they were still above the ISO 20685 limit, they were much closer than the results obtained for human participants. The main cause of the differences between the two methods is the time required for the 3D system to acquire the data. The involuntary body sway of human participants is more difficult to control when the time span is too long.


A spin-thermodynamic approach to characterize spin dynamics in TEMPO-based samples for dissolution DNP at 7 T field.
The spin dynamics of dissolution DNP samples consisting of 4.5 M [13C]urea in a mixture of (1/1)Vol glycerol/water using 4-Oxo-TEMPO as a radical was investigated. We analyzed the DNP dynamics as function of radical concentration at 7 T and 3.4 T static magnetic field as well as function of deuteration of the solvent matrix at the high field. The spin dynamics could be reproduced in all cases, at least qualitatively, by a thermodynamic model based on spin temperatures of the nuclear Zeeman baths and an electron non-Zeeman (dipolar) bath. We find, however, that at high field (7 T) and low radical concentrations (25 mM) the nuclear spins do not reach the same spin temperature indicating a weak coupling of the two baths. At higher radical concentrations, as well as for all radical concentrations at low field (3.4 T), the two nuclear Zeeman baths reach the same spin temperature within experimental errors. Additionally, the spin system was prepared with different initial conditions. For these cases, the thermodynamic model was able to predict the time evolution of the system well. While the DNP profiles do not give clear indications to a specific polarization transfer mechanism, at high field (7 T) increased coupling is seen. The EPR line shapes cannot clarify this in absence of ELDOR type experiments, nevertheless DNP profiles and dynamics under frequency-modulated microwave irradiation illustrate the expected increase in coupling between electrons with increasing radical concentration.


Novel Undamped Gapless Plasmon Mode in a Tilted Type-II Dirac Semimetal.
We predict the existence of a novel long-lived gapless plasmon mode in a type-II Dirac semimetal (DSM). This gapless mode arises from the out-of-phase oscillations of the density fluctuations in the electron and the hole pockets of a type-II DSM. It originates beyond a critical wave vector along the direction of the tilt axis, owing to the momentum separation of the electron and hole pockets. A similar out-of-phase plasmon mode arises in other multicomponent charged fluids as well, but generally, it is Landau damped and lies within the particle-hole continuum. In the case of a type-II DSM, the open Fermi surface prohibits low-energy finite momentum single-particle excitations, creating a "gap" in the particle-hole continuum. The gapless plasmon mode lies within this particle-hole continuum gap and, thus, it is protected from Landau damping.


Polyphyletic origins of schizothoracine fish (Cyprinidae, Osteichthyes) and adaptive evolution in their mitochondrial genomes.
The schizothoracine fish, also called snow trout, are members of the Cyprinidae, and are the most diversified teleost fish in the Qinghai-Tibetan Plateau (QTP). Clarifying the evolutionary history of the schizothoracine fish is therefore important for better understanding the biodiversity of the QTP. Although morphological and molecular phylogenetic studies have supported the monophyly of the Schizothoracinae, a recent molecular phylogenetic study based on the mitochondrial genome questioned the monophyly of this taxon. However, the phylogenetic analysis of that study was on the basis of only three schizothoracine species, and the support values were low. In this report, we inferred the phylogenetic tree on the basis of mitochondrial genome data including 21 schizothoracine species and five closely related species, and the polyphyletic origins of the Schizothoracinae were strongly supported. The tree further suggests that the Schizothoracinae consists of two clades, namely the "morphologically specialized clade" and the "morphologically primitive clade", and that these two clades migrated independently of each other to the QTP and adapted to high altitude. We also detected in their mitochondrial genomes strong signals of positive selection, which probably represent evidence of high-altitude adaptation. In the case of the morphologically specialized clade, positive selection mainly occurred during the Late Paleocene to the Early Oligocene. Its migration also seems to have occurred in the Early Eocene, and this timing is consistent with the drastic uplifting of the QTP. On the other hand, positive selection in the morphologically primitive clade has mainly occurred since the Late Miocene. Because its members are thought to have migrated to the QTP recently, it is possible that they are now undergoing high-altitude adaptation.


The association between low vitamin D levels and suicide attempts in adolescents.
Psychiatric disorders are the most common cause of suicide attempts. Some studies have shown there is a relationship between low vitamin D levels and psychiatric disorders. In this study, we examined the relationship between suicidal behavior and vitamin D levels in adolescents. This study included 215 patients who presented to the pediatric emergency department due to a suicide attempt (patient group) and 200 healthy individuals (control group). Demographic and clinical features of both groups were recorded, and serum vitamin D, calcium, and phosphorus levels were measured. The groups were compared in terms of these factors. All data were analyzed using the SPSS 20.0 (SPSS Inc., Illinois, USA) software program. The mean vitamin D level was 19.4 ± 10 ng/mL in the control group and 12.3 ± 6 ng/mL in the patient group (t = 8.8 and P = .01). The mean serum total calcium level was 9.9 ± 0.3 mg/dL in the control group and 9.4 ± 0.5 mg/dL in the patient group (P < .01). Vitamin D deficiency, which is a treatable condition, may be one of the causes of suicidal behavior in adolescents. Therefore, we believe that physicians who treat adolescents should consider vitamin D levels in routine examinations.


Enhancement of the results of neck liposuction with the FAMI technique.
Submental liposuction is an excellent procedure for improving the aging neck by reducing the cervicomental angle and increasing the definition of the mandibular border. However, it does not address the loss of volume of the chin and perioral areas caused by atrophy of hard and soft tissues. In this study, thirty patients underwent concomitant submental tumescent liposuction and fat augmentation with the FAMI (fat autograft muscle injection) technique in order to assess short-term results and complications associated with these two relatively noninvasive procedures. All patients had improvement in the cervicomental border, a smoother mandibular border, and a more proportioned chin following 3-5 days of swelling. Patients followed for 6 months to one year had long term retention of fat. There were no significant complications. In this preliminary series, submental tumescent liposuction with FAMI provided enhanced aesthetic results with little downtime and minimal complications.


A Core Set of Outcome Measures for Adults With Neurologic Conditions Undergoing Rehabilitation: A CLINICAL PRACTICE GUIDELINE.
Use of outcome measures (OMs) in adult neurologic physical therapy is essential for monitoring changes in a patient's status over time, quantifying observations and patient-reported function, enhancing communication, and increasing the efficiency of patient care. OMs also provide a mechanism to compare patient and organizational outcomes, examine intervention effectiveness, and generate new knowledge. This clinical practice guideline (CPG) examined the literature related to OMs of balance, gait, transfers, and patient-stated goals to identify a core set of OMs for use across adults with neurologic conditions and practice settings. To determine the scope of this CPG, surveys were conducted to assess the needs and priorities of consumers and physical therapists. OMs were identified through recommendations of the Academy of Neurologic Physical Therapy's Evidence Database to Guide Effectiveness task forces. A systematic review of the literature on the OMs was conducted and additional OMs were identified; the literature search was repeated on these measures. Articles meeting the inclusion criteria were critically appraised by 2 reviewers using a modified version of the COnsensus-based Standards for the selection of health Measurement INstruments. (COSMIN) checklist. Methodological quality and the strength of statistical results were determined. To be recommended for the core set, the OMs needed to demonstrate excellent psychometric properties in high-quality studies across neurologic conditions. Based on survey results, the CPG focuses on OMs that have acceptable clinical utility and can be used to assess change over time in a patient's balance, gait, transfers, and patient-stated goals. Strong, level I evidence supports the use of the Berg Balance Scale to assess changes in static and dynamic sitting and standing balance and the Activities-specific Balance Confidence Scale to assess changes in balance confidence. Strong to moderate evidence supports the use of the Functional Gait Assessment to assess changes in dynamic balance while walking, the 10 meter Walk Test to assess changes in gait speed, and the 6-Minute Walk Test to assess changes in walking distance. Best practice evidence supports the use of the 5 Times Sit-to-Stand to assess sit to standing transfers. Evidence was insufficient to support use of a specific OM to assess patient-stated goals across adult neurologic conditions. Physical therapists should discuss the OM results with patients and collaboratively decide how the results should inform the plan of care. The recommendations included in this CPG are intended as a guide for clinicians, patients, educators, and researchers to improve rehabilitation care and its impact on adults with neurologic conditions. The contents of this CPG were developed with support from the APTA and the Academy of Neurologic Physical Therapy (ANPT). The Guideline Development Group (GDG) used a rigorous review process and was able to freely express its findings and recommendations without influence from the APTA or the ANPT. The authors declare no competing interest.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A214.


Microsurgical anatomy of the subthalamic nucleus: correlating fiber dissection results with 3-T magnetic resonance imaging using neuronavigation.
Despite the extensive use of the subthalamic nucleus (STN) as a deep brain stimulation (DBS) target, unveiling the extensive functional connectivity of the nucleus, relating its structural connectivity to the stimulation-induced adverse effects, and thus optimizing the STN targeting still remain challenging. Mastering the 3D anatomy of the STN region should be the fundamental goal to achieve ideal surgical results, due to the deep-seated and obscure position of the nucleus, variable shape and relatively small size, oblique orientation, and extensive structural connectivity. In the present study, the authors aimed to delineate the 3D anatomy of the STN and unveil the complex relationship between the anatomical structures within the STN region using fiber dissection technique, 3D reconstructions of high-resolution MRI, and fiber tracking using diffusion tractography utilizing a generalized q-sampling imaging (GQI) model. Fiber dissection was performed in 20 hemispheres and 3 cadaveric heads using the Klingler method. Fiber dissections of the brain were performed from all orientations in a stepwise manner to reveal the 3D anatomy of the STN. In addition, 3 brains were cut into 5-mm coronal, axial, and sagittal slices to show the sectional anatomy. GQI data were also used to elucidate the connections among hubs within the STN region. The study correlated the results of STN fiber dissection with those of 3D MRI reconstruction and tractography using neuronavigation. A 3D terrain model of the subthalamic area encircling the STN was built to clarify its anatomical relations with the putamen, globus pallidus internus, globus pallidus externus, internal capsule, caudate nucleus laterally, substantia nigra inferiorly, zona incerta superiorly, and red nucleus medially. The authors also describe the relationship of the medial lemniscus, oculomotor nerve fibers, and the medial forebrain bundle with the STN using tractography with a 3D STN model. This study examines the complex 3D anatomy of the STN and peri-subthalamic area. In comparison with previous clinical data on STN targeting, the results of this study promise further understanding of the structural connections of the STN, the exact location of the fiber compositions within the region, and clinical applications such as stimulation-induced adverse effects during DBS targeting.


Novel hydrolysis-resistant analogues of cyclic ADP-ribose: modification of the "northern" ribose and calcium release activity.
Three novel analogues modified in the "northern" ribose (ribose linked to N1 of adenine) of the Ca(2+) mobilizing second messenger cyclic adenosine diphosphoribose, termed 2"-NH(2)-cyclic adenosine diphosphoribose, cyclic adenosine diphospho-carbocyclic-ribose, and 8-NH(2)-cyclic adenosine diphospho-carbocyclic-ribose, were synthesized (chemoenzymatically and by total synthesis) and spectroscopically characterized, and the pK(a) values for the 6-amino/imino transition were determined in two cases. The biological activity of these analogues was determined in permeabilized human Jurkat T-lymphocytes. 2"-NH(2)-cyclic adenosine diphosphoribose mediated Ca(2+) release was slightly more potent than that of the endogenous cyclic adenosine diphosphoribose in terms of the concentration-reponse relationship. Both compounds released Ca(2+) from the same intracellular Ca(2+) pool. In addition, the control compound 2"-NH(2)-adenosine diphosphoribose was almost without effect. In contrast, only at much higher concentrations (> or =50 microM) did the "northern" carbocyclic analogue, cyclic adenosine diphospho-carbocyclic-ribose, significantly release Ca(2+) from permeabilized T cells, whereas the previously reported "southern" carbocyclic analogue, cyclic aristeromycin diphosphoribose, was slightly more active than the endogenous cyclic adenosine diphosphoribose. Likewise, 8-NH(2)-cyclic adenosine diphospho-carbocyclic-ribose, expected to antagonize Ca(2+) release as demonstrated previously for 8-NH(2)-cyclic adenosine diphosphoribose, did not inhibit cyclic adenosine diphosphoribose mediated Ca(2+) release. This indicates that the 2"-NH(2)-group substitutes well for the 2"-OH-group it replaces; it may be oriented toward the outside of the putative cyclic adenosine diphosphoribose receptor binding domain and/or it can potentially also engage in H bonding interactions with residues of that domain. In sharp contrast to this, replacement of the endocyclic furanose oxygen atom by CH(2) in a carbocyclic system obviously interferes with a crucial element of interaction between cyclic adenosine diphosphoribose and its receptor in T-lymphocytes.


Multimodal representations of person identity individuated with fMRI.
Recognizing the identity of a person is fundamental to guide social interactions. We can recognize the identity of a person looking at her face, but also listening to her voice. An important question concerns how visual and auditory information come together, enabling us to recognize identity independently of the modality of the stimulus. This study reports converging evidence across univariate contrasts and multivariate classification showing that the posterior superior temporal sulcus (pSTS), previously known to encode polymodal visual and auditory representations, encodes information about person identity with invariance within and across modality. In particular, pSTS shows selectivity for faces, selectivity for voices, classification of face identity across image transformations within the visual modality, and classification of person identity across modality.


Mapping and exploring variation in post-fire vegetation recovery following mixed severity wildfire using airborne LiDAR.
There is a public perception that large high-severity wildfires decrease biodiversity and increase fire hazard by homogenizing vegetation composition and increasing the cover of mid-story vegetation. But a growing literature suggests that vegetation responses are nuanced. LiDAR technology provides a promising remote sensing tool to test hypotheses about post-fire vegetation regrowth because vegetation cover can be quantified within different height strata at fine scales over large areas. We assess the usefulness of airborne LiDAR data for measuring post-fire mid-story vegetation regrowth over a range of spatial resolutions (10 × 10 m, 30 × 30 m, 50 × 50 m, 100 × 100 m cell size) and investigate the effect of fire severity on regrowth amount and spatial pattern following a mixed severity wildfire in Warrumbungle National Park, Australia. We predicted that recovery would be more vigorous in areas of high fire severity, because park managers observed dense post-fire regrowth in these areas. Moderate to strong positive associations were observed between LiDAR and field surveys of mid-story vegetation cover between 0.5-3.0 m. Thus our LiDAR survey was an apt representation of on-ground vegetation cover. LiDAR-derived mid-story vegetation cover was 22-40% lower in areas of low and moderate than high fire severity. Linear mixed-effects models showed that fire severity was among the strongest biophysical predictors of mid-story vegetation cover irrespective of spatial resolution. However much of the variance associated with these models was unexplained, presumably because soil seed banks varied at finer scales than our LiDAR maps. Dense patches of mid-story vegetation regrowth were small (median size 0.01 ha) and evenly distributed between areas of low, moderate and high fire severity, demonstrating that high-severity fires do not homogenize vegetation cover. Our results are relevant for ecosystem conservation and fire management because they: indicate that native vegetation are responsive and resilient to high-severity fire, and show the usefulness of remote sensing tools such as LiDAR to monitor post-fire vegetation recovery over large areas in situ.


Apple polyphenol extracts protect against aspirin-induced gastric mucosal damage in rats.
The protective role of two apple polyphenol extracts, Douglas-FB (FB) and Douglas-EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague-Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10-day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10(-2) m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10-day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats.


Florivore impacts on plant reproductive success and pollinator mortality in an obligate pollination mutualism.
Florivores are present in many pollination systems and can have direct and indirect effects on both plants and pollinators. Although the impact of florivores are commonly examined in facultative pollination mutualisms, their effects on obligate mutualism remain relatively unstudied. Here, we used experimental manipulations and surveys of naturally occurring plants to assess the effect of florivory on the obligate pollination mutualism between yuccas and yucca moths. Yucca filamentosa (Agavaceae) is pollinated by the moth Tegeticula cassandra (Lepidoptera: Prodoxidae), and the mutualism also attracts two florivores: a generalist, the leaf-footed bug Leptoglossus phyllopus (Hemiptera: Coreidae), and a specialist, the beetle Hymenorus densus (Coleoptera: Tenebrionidae). Experimental manipulations of leaf-footed bug densities on side branches of Y. filamentosa inflorescences demonstrated that feeding causes floral abscission but does not reduce pollen or seed production in the remaining flowers. Similar to the leaf-footed bugs, experimental manipulations of beetle densities within individual flowers demonstrated that beetle feeding also causes floral abscission, but, in addition, the beetles also cause a significant reduction in pollen availability. Path analyses of phenotypic selection based on surveys of naturally occurring plants revealed temporal variation in the plant traits important to plant fitness and the effects of the florivores on fitness. Leaf-footed bugs negatively impacted fitness when fewer plants were flowering and leaf-footed bug density was high, whereas beetles had a positive effect on fitness when there were many plants flowering and their densities were low. This positive effect was likely due to adult beetles consuming yucca moth eggs while having a negligible effect on floral abscission. Together, the actions of both florivores either augmented the relationship of plant traits and fitness or slightly weakened the relationship. Overall, the results suggest that, although florivores are always present during flowering, the impact of florivores on phenotypic selection in yuccas is strongly mitigated by changes in their densities on plants from year to year. In contrast, both florivores consistently influenced pollinator larval mortality through floral abscission, and H. densus beetles additionally via the consumption of pollinator eggs.


International survey for assessing COVID-19's impact on fear and health: study protocol.
COVID-19, caused by the SARS-CoV-2, has been one of the most highly contagious and rapidly spreading virus outbreak. The pandemic not only has catastrophic impacts on physical health and economy around the world, but also the psychological well-being of individuals, communities and society. The psychological and social impacts of the COVID-19 pandemic internationally have not been well described. There is a lack of international study assessing health-related impacts of the COVID-19 pandemic, especially on the degree to which individuals are fearful of the pandemic. Therefore, this study aims to (1) assess the health-related impact of the COVID-19 pandemic in community-dwelling individuals around the world; (2) determine the extent various communities are fearful of COVID-19 and (3) identify perceived needs of the population to prepare for potential future pandemics. This global study involves 30 countries. For each country, we target at least 500 subjects aged 18 years or above. The questionnaires will be available online and in local languages. The questionnaires include assessment of the health impacts of COVID-19, perceived importance of future preparation for the pandemic, fear, lifestyles, sociodemographics, COVID-19-related knowledge, e-health literacy, out-of-control scale and the Patient Health Questionnaire-4. Descriptive statistics will be used to describe participants' characteristics, perceptions on the health-related impacts of COVID-19, fear, anxiety and depression, lifestyles, COVID-19 knowledge, e-health literacy and other measures. Univariable and multivariable regression models will be used to assess the associations of covariates on the outcomes. The study has been reviewed and approved by the local ethics committees in participating countries, where local ethics approval is needed. The results will be actively disseminated. This study aims to map an international perspective and comparison for future preparation in a pandemic.


Risk Stratification of Older Adults Who Present to the Emergency Department With Syncope: The FAINT Score.
Older adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes. We performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome. We enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670). Among older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.


Persistent problems of access to appropriate, affordable TB services in rural China: experiences of different socio-economic groups.
Large-scale Tuberculosis (TB) control programmes in China have been hailed a success. Concerns remain, however, about whether the programme is reaching all sections of the population, particularly poorer groups within rural communities, and whether there are hidden costs. This study takes a household perspective to investigate receipt of appropriate care and affordability of services for different socio-economic groups with TB symptoms in rural China. Secondary analysis of Chinese National Household Health Survey for 2003: 40,000 rural households containing 143,991 individuals, 2,308 identified as TB suspects. use of services and expenditure of TB suspects, by gender and socio-economic position, indicated by household income, education, material assets, and insurance status. 37% of TB suspects did not seek any professional care, with low-income groups less likely to seek care than more affluent counterparts. Of those seeking care, only 35% received any of the recommended diagnostic tests. Of the 182 patients with a confirmed TB diagnosis, 104 (57%) received treatment at the recommended level, less likely if lacking health insurance or material assets. The burden of payment for services amounted to 45% of annual household income for the low-income group, 16% for the high-income group. Access to appropriate, affordable TB services is still problematic in some rural areas of China, and receipt of care and affordability declines with declining socio-economic position. These findings highlight the current shortcomings of the national TB control programme in China and the formidable challenge it faces if it is to reach all sections of the population, including the poor with the highest burden of disease.


Sigmoid colonic perforation and pelvic abscess complicating biliary stent migration.
Endoscopically placed biliary stents are a well-established procedure for the treatment of benign and malignant causes of obstructive jaundice in patients unfit for definitive surgical intervention. Stent migration has been described, though in most instances the stent will pass or remain in the bowel lumen for extended periods of time. Only a few cases of clinically significant complications of stent migration have been reported. This is the first case report of a pelvic abscess complicating stenting for choledocholithiasis. As the numbers of stenting procedures continue to increase it may be anticipated that the numbers of complications will similarly increase.


Cranial growth and variation in edmontosaurs (Dinosauria: Hadrosauridae): implications for latest Cretaceous megaherbivore diversity in North America.
The well-sampled Late Cretaceous fossil record of North America remains the only high-resolution dataset for evaluating patterns of dinosaur diversity leading up to the terminal Cretaceous extinction event. Hadrosaurine hadrosaurids (Dinosauria: Ornithopoda) closely related to Edmontosaurus are among the most common megaherbivores in latest Campanian and Maastrichtian deposits of western North America. However, interpretations of edmontosaur species richness and biostratigraphy have been in constant flux for almost three decades, although the clade is generally thought to have undergone a radiation in the late Maastrichtian. We address the issue of edmontosaur diversity for the first time using rigorous morphometric analyses of virtually all known complete edmontosaur skulls. Results suggest only two valid species, Edmontosaurus regalis from the late Campanian, and E. annectens from the late Maastrichtian, with previously named taxa, including the controversial Anatotitan copei, erected on hypothesized transitional morphologies associated with ontogenetic size increase and allometric growth. A revision of North American hadrosaurid taxa suggests a decrease in both hadrosaurid diversity and disparity from the early to late Maastrichtian, a pattern likely also present in ceratopsid dinosaurs. A decline in the disparity of dominant megaherbivores in the latest Maastrichtian interval supports the hypothesis that dinosaur diversity decreased immediately preceding the end Cretaceous extinction event.


A brief history of bioinformatics.
It is easy for today's students and researchers to believe that modern bioinformatics emerged recently to assist next-generation sequencing data analysis. However, the very beginnings of bioinformatics occurred more than 50 years ago, when desktop computers were still a hypothesis and DNA could not yet be sequenced. The foundations of bioinformatics were laid in the early 1960s with the application of computational methods to protein sequence analysis (notably, de novo sequence assembly, biological sequence databases and substitution models). Later on, DNA analysis also emerged due to parallel advances in (i) molecular biology methods, which allowed easier manipulation of DNA, as well as its sequencing, and (ii) computer science, which saw the rise of increasingly miniaturized and more powerful computers, as well as novel software better suited to handle bioinformatics tasks. In the 1990s through the 2000s, major improvements in sequencing technology, along with reduced costs, gave rise to an exponential increase of data. The arrival of 'Big Data' has laid out new challenges in terms of data mining and management, calling for more expertise from computer science into the field. Coupled with an ever-increasing amount of bioinformatics tools, biological Big Data had (and continues to have) profound implications on the predictive power and reproducibility of bioinformatics results. To overcome this issue, universities are now fully integrating this discipline into the curriculum of biology students. Recent subdisciplines such as synthetic biology, systems biology and whole-cell modeling have emerged from the ever-increasing complementarity between computer science and biology.


Where techno-science meets poverty: medical research and the economy of blood in The Gambia, West Africa.
This paper considers how internationally supported medical research is understood and interpreted by its actual and potential study subjects, exposing the limits to bioethical discourses amidst economic inequalities and contrasting socio-cultural worlds. It focuses on the Medical Research Council (MRC) Laboratories in The Gambia and particularly their Pneumococcal Vaccine Trial (PVT) that was conducted jointly with the Gambian government during 2001-2004. In many respects this was an exemplar of international best practice in trial communication and informed consent procedures. Yet ethnographic and survey research finds that Gambian parents' perspectives on participation are shaped not by trial specificities, but by broader, historically shaped views and experiences of the MRC as an institution. There is a pervasive view that the MRC offers good, free medication to participants, but that it also 'steals blood'. Widespread concerns with blood-stealing emerge from local frames of understanding in which blood is treated as a tradeable good, in which blood accumulation and depletion in bodily processes relates to its exchange in hospital and medical research practices, and in which transactions can be more or less (un)reasonable. Yet such thinking, rooted in an 'economy of blood', has been overlooked by medical research staff and indeed by historians and anthropologists of Africa whose analyses of blood-stealing have been overly transfixed on rumour and the occult. This paper argues that such cultural framings, which guide local critical commentary on trans-national research orders, require serious attention and need to inform open dialogues between scientists and the public if medical research in resource-poor settings is to continue to be sustainable and politically legitimate.


Marek's disease virus Meq transforms chicken cells via the v-Jun transcriptional cascade: a converging transforming pathway for avian oncoviruses.
Marek's disease virus (MDV) is a highly pathogenic and oncogenic herpesvirus of chickens. MDV encodes a basic leucine zipper (bZIP) protein, Meq (MDV EcoQ). The bZIP domain of Meq shares homology with Jun/Fos, whereas the transactivation/repressor domain is entirely different. Increasing evidence suggests that Meq is the oncoprotein of MDV. Direct evidence that Meq transforms chicken cells and the underlying mechanism, however, remain completely unknown. Taking advantage of the DF-1 chicken embryo fibroblast transformation system, a well established model for studying avian sarcoma and leukemia oncogenes, we probed the transformation properties and pathways of Meq. We found that Meq transforms DF-1, with a cell morphology akin to v-Jun and v-Ski transformed cells, and protects DF-1 from apoptosis, and the transformed cells are tumorigenic in chorioallantoic membrane assay. Significantly, using microarray and RT-PCR analyses, we have identified up-regulated genes such as JTAP-1, JAC, and HB-EGF, which belong to the v-Jun transforming pathway. In addition, c-Jun was found to form stable dimers with Meq and colocalize with it in the transformed cells. RNA interference to Meq and c-Jun down-modulated the expression of these genes and reduced the growth of the transformed DF-1, suggesting that Meq transforms chicken cells by pirating the Jun pathway. These data suggest that avian herpesvirus and retrovirus oncogenes use a similar strategy in transformation and oncogenesis.


Aggression and violence in healthcare and its impact on nursing students: A narrative review of the literature.
Aggression and violence is a significant social problem in many countries and an increasing problem in healthcare settings in which nurses are particularly vulnerable. The literature suggests that aggression and violence has a significant negative impact upon nurses and potentially upon nursing students and can result in these staff members experiencing stress as a direct result of these adverse events. The literature suggests that there is confusion over what constitutes aggression and violence in the workplace and therefore a true lack of understanding of the scale of the problem relating to nursing students. This review proposes that nursing students are indeed at significant risk of aggression and violence in the clinical setting which has the potential to significantly impact their role as a novice carer. Furthermore, aggression and violence can manifest negative stress responses in individuals, therefore, the potential for nursing students to cope with stressful situations shall be presented.


Assessing the Quality, Feasibility, and Efficacy of Electronic Patient Platforms Designed to Support Adolescents and Young Adults With Cancer: A Systematic Review Protocol.
A range of innovative websites, mobile technologies, eHealth and mHealth platforms have emerged to support adolescents and young adults (AYAs) with cancer. Previous reviews have identified these various applications and solutions, but no review has summarized the quality, feasibility, and efficacy of existing patient platforms (inclusive of websites, mobile technologies, mHealth and eHealth platforms) developed specifically for young people with cancer. This paper describes the design of a protocol to conduct a review of published studies or reports which describe or report on an existing platform designed specifically for AYAs who have had a cancer diagnosis. A search string was developed using a variety of key words and Medical Subject Heading and applied to bibliographic databases. General data (sample characteristics, patient platform development, design and, if applicable, pilot testing outcomes) will be extracted from reports and studies. Drawing on a previously developed coding schematic, the identified patient platforms will be coded for mode of delivery into (1) automated functions, (2) communicative functions, and (3) use of supplementary modes. An adapted version of the Mobile App Rating Scale (MARS) will be used to assess the of quality of each identified patient platform. The methodological quality of included studies will be assessed using the Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (QualSyst). Both authors will independently screen eligible studies for final inclusion and will both be responsible for data extraction and appraisal. Data will be synthesized narratively to provide an overview of identified patient platforms. The review began in October 2016 and is currently in progress. The review paper will be submitted for peer-review and publication in the summer of 2017. This review will be unique in its focus on assessing, where possible, the quality and efficacy of patient platforms for adolescents and young adults diagnosed with cancer. Results generated from this review will provide an invaluable insight into the utility of modern technology in supporting young people with cancer.


Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register.
Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA. Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs). Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69). These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.


Clinical outcome after coronary artery revascularization and lung transplantation.
Presence of coronary artery disease (CAD) in otherwise eligible lung transplant candidates is considered a contraindication to lung transplantation. We reviewed the clinical outcome of our experience in lung transplant recipients with operable coronary artery disease and normal left ventricular function. Medical records of all transplant recipients with coronary artery disease were reviewed. Data analyzed include demographics, coronary angiograms, coronary artery revascularization procedure, and clinical outcome after lung transplantation. Between April 1992 and August 2001, 354 lung transplant procedures were performed. Eighteen patients (5%) had significant CAD (greater than 50% stenoses). Six male patients (mean age 59 years) underwent percutaneous transluminal coronary angioplasty/stent and after lung transplantation all were discharged after a median hospital stay of 8.5 days. All recipients are alive at a median follow-up time of 14.5 months after their transplant. Twelve male patients (mean age 58 years) had combined coronary artery bypass grafting and lung transplantation. All recipients were discharged after a median hospital stay of 16 days. Nine recipients are alive at a median follow-up time of 7.5 months after transplant. One-year survival by the Kaplan-Meier method is 88% for the 18 patients with coronary artery disease who underwent revascularization and lung transplantation. Despite the traditional criteria of excluding all eligible transplant candidates due to coronary artery disease, coronary revascularization in select candidates with favorable anatomy and normal left ventricular function can allow patients to undergo lung transplantation with acceptable outcomes.


Assessing markers from ambulatory laboratory tests for predicting high-risk patients.
This exploratory study used outpatient laboratory test results from electronic health records (EHRs) for patient risk assessment and evaluated whether risk markers based on laboratory results improve the performance of diagnosis- and pharmacy-based predictive models for healthcare outcomes. Observational study of a patient cohort over 2 years. We used administrative claims and EHR data over a 2-year period for a population of continuously insured patients in an integrated health system who had at least 1 ambulatory visit during the first year. We performed regression tree analyses to develop risk markers from frequently ordered outpatient laboratory tests. We added these risk markers to demographic and Charlson Comorbidity Index models and 3 models from the Johns Hopkins Adjusted Clinical Groups system to predict individual cost, inpatient admission, and high-cost patients. We evaluated the predictive and discriminatory performance of 5 lab-enhanced models. Our study population included 120,844 patients. Adding laboratory markers to base models improved R2 predictions of costs by 0.1% to 3.7%, identification of high-cost patients by 3.4% to 121%, and identification of patients with inpatient admissions by 1.0% to 188% for the demographic model. The addition of laboratory risk markers to comprehensive risk models, compared with simpler models, resulted in smaller improvements in predictive power. The addition of laboratory risk markers can significantly improve the identification of high-risk patients using models that include age, gender, and a limited number of morbidities; however, models that use comprehensive risk measures may be only marginally improved.


A comparison of early gastric and post-pyloric feeding in critically ill patients: a meta-analysis.
To investigate the potential beneficial and adverse effects of early post-pyloric feeding compared with gastric feeding in critically ill adult patients with no evidence of impaired gastric emptying. Randomised controlled studies comparing gastric and post-pyloric feeding in critically ill adult patients from Cochrane Controlled Trial Register (2005 issue 3), EMBASE and MEDLINE databases (1966 to 1 October 2005) without any language restriction were included. Two reviewers reviewed the quality of the studies and performed data extraction independently. Eleven randomised controlled studies with a total of 637 critically ill adult patients were considered. The mortality (relative risk [RR] 1.01, 95% CI 0.76-1.36, p=0.93; I2=0%) and risk of aspiration or pneumonia (RR 1.28, 95% CI 0.91-1.80, p=0.15; I2=0%) were not significantly different between patients treated with gastric or post-pyloric feeding. The effect of post-pyloric feeding on the risk of pneumonia or aspiration was similar when studies were stratified into those with and those without the use of concurrent gastric decompression (RR ratio 0.95, 95% CI 0.48-1.91, p=0.89). The risk of diarrhoea and the length of intensive care unit stay (weighted mean difference in days -1.46, 95% CI -3.74 to 0.82, p=0.21; I2=24.6%) were not statistically different. The gastric feeding group had a much lower risk of experiencing feeding tube placement difficulties or blockage (0 vs 9.6%, RR 0.13, 95% CI 0.04-0.44, p=0.001; I2=0%). Early use of post-pyloric feeding instead of gastric feeding in critically ill adult patients with no evidence of impaired gastric emptying was not associated with significant clinical benefits.


Hepatitis E virus is highly prevalent in the Danish pig population.
The objective of this study was to examine the prevalence of Hepatitis E virus (HEV) in the Danish pig population. Faecal samples from 97 pigs, 1-5 months of age were analysed for HEV RNA by a new PriProET real time RT-PCR assay. In addition, serum samples from 71 sow herds were screened for the presence of anti-HEV IgG antibodies by ELISA. The genotype of the detected HEV positive samples was estimated based on the melting temperature obtained by the PriProET real time RT-PCR assay. The HEV prevalence of faecal samples was 55.0% and 49.5% for herds and animals, respectively. A HEV IgG prevalence of 91.5% was found for the sow herds which correspond to 73.2% of the sows. The PriProET assay indicated that all HEV positive samples belonged to genotype 3 or 4, which is consistent with the observation of genotype 3 as dominant in European pigs. This is the first study showing that HEV is highly prevalent in the Danish pig population. The abundant presence of HEV in Danish pigs and the known high similarity between HEV isolates from pigs and humans support previous reports indicating possible zoonotic transmission of HEV.


Impact of leptin-mediated sympatho-activation on cardiovascular function in obese mice.
Although the anorexic effects of leptin are lost in obesity, leptin-mediated sympatho-activation is preserved. The cardiovascular consequences of leptin-mediated sympatho-activation in obesity are poorly understood. We tested the hypothesis that 32 weeks of high-fat diet (HFD) induces metabolic leptin resistance but preserves leptin-mediated sympatho-activation of the cardiovascular system. HFD in mice significantly increased body weight and plasma leptin concentrations but significantly reduced the anorexic effects of leptin. HFD increased heart rate, stroke volume, cardiac output, and plasma aldosterone levels but not blood pressure. As reflected by the contractile response to phenylephrine measured both in vivo and ex vivo, vascular adrenergic reactivity was reduced by HFD, suggesting that reductions in sympathetic tone to the periphery vasculature may mitigate sympatho-activation of the heart and the renin-angiotensin-aldosterone system. Tachyphylaxis was partially restored by symptho-inhibition and not present in ob/ob and db/db mice, despite obesity, arguing for a sympatho-mediated and leptin-specific mechanism. Although infusion of leptin in HFD mice had no effect on heart rate or blood pressure, it further increased aldosterone levels and further reduced vascular adrenergic tone in the absence of weight loss, indicating persistent leptin-mediated stimulation of the cardiovascular system in obesity. In conclusion, these data indicate that, despite metabolic leptin resistance, leptin-mediated stimulation of the heart, the vasculature, and aldosterone production persists in obesity. Blood pressure effects in response to leptin may be limited by a tachyphylactic response in the circulation, suggesting that failure of adrenergic desensitization may be a requisite step for hypertension in the context of obesity.


The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis.
Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes and in a growing number of diseases, controlling gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, protein translation and turnover. The fundamental role of lncRNAs in central nervous system (CNS) is becoming increasingly evident. LncRNAs are abundantly expressed in mammalian CNS in a specific spatio-temporal manner allowing a quick response to environmental/molecular changes. This article reviews the biology and mechanisms of action of lncRNAs underlying their potential role in CNS and in some neurodegenerative diseases. an increasing number of studies report on lncRNAs involvement in different molecular mechanisms of gene expression modulation in CNS, from neural stem cell differentiation mainly by chromatin remodeling, to control of neuronal activities. More recently, lncRNAs have been implicated in neurodegenerative diseases, including Alzheimer's Disease, where the role of BACE1-AS lncRNA has been widely defined. BACE1-AS levels are up-regulated in AD brains where BACE1-AS acts by stabilizing BACE1 mRNA thereby increasing BACE1 protein content and Aβ42 formation. In Frontotemporal dementia and Amyotrophic lateral sclerosis the lncRNAs NEAT1_2 and MALAT1 co-localize at nuclear paraspeckles with TDP-43 and FUS proteins and their binding to TDP-43 is markedly increased in affected brains. In Parkinson's Disease the lncRNA UCHL1-AS1 acts by directly promoting translation of UCHL1 protein leading to perturbation of the ubiquitin-proteasome system. Different lncRNAs, such as HTT-AS, BDNF-AS and HAR1, were found to be dysregulated in their expression also in Huntington's Disease. In Fragile X syndrome (FXS) and Fragile X tremor/ataxia syndrome (FXTAS) patients, the presence of CGG repeats expansion alters the expression of the lncRNAs FMR1-AS1 and FMR6. Interestingly, they are expressed in peripheral blood leukocytes, suggesting these lncRNAs may represent biomarkers for FXS/FXTAS early detection and therapy. Finally, the identification of the antisense RNAs SCAANT1-AS and ATXN8OS in spinocerebellar ataxia 7 and 8, respectively, suggests that very different mechanisms of action driven by lncRNAs may trigger neurodegeneration in these disorders. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms which deserve further investigation. The evaluation of their diagnostic significance and therapeutic potential could also address the setting up of novel treatments in diseases where no cure is available to date.


Chorioretinal folds. A comparison of unilateral and bilateral cases.
We retrospectively reviewed the records, photographs, and fluorescein angiograms of patients with chorioretinal folds to compare features of unilateral and bilateral involvement. We studied 78 eyes of 54 patients and found that 30 (56%) of these patients had unilateral folds and 24 (44%) had bilateral folds. No significant difference was found in comparing visual acuity, refractive error, age, or race in the unilateral vs the bilateral cases. There were significantly more women in the bilateral group (P = .043). The frequency of causes of unilateral cases differed from bilateral cases, but this could not be statistically proven owing to our small sample size. This analysis contains the largest number of chorioretinal folds reported in the literature, and is the first attempt to compare unilateral and bilateral cases.


Increased neural response to fear in patients recovered from depression: a 3T functional magnetic resonance imaging study.
Previous imaging studies have revealed that acute major depression is characterized by altered neural responses to negative emotional stimuli. Typically, responses in limbic regions such as the amygdala are increased while activity in cortical regulatory regions such as the dorsolateral prefrontal cortex (DLPFC) is diminished. Whether these changes persist in unmedicated recovered patients is unclear. We used functional magnetic resonance imaging to examine neural responses to emotional faces in a facial expression-matching task in 16 unmedicated recovered depressed patients and 21 healthy controls. Compared with controls, recovered depressed patients had increased responses bilaterally to fearful faces in the DLPFC and right caudate. Responses in the amygdala did not distinguish the groups. Our findings indicate that clinical recovery from depression is associated with increased activity in the DLPFC to negative emotional stimuli. We suggest that this increase may reflect a compensatory cortical control mechanism with the effect of limiting emotional dysregulation in limbic regions such as the amygdala.