Herpes Simplex Virus Type 1 Clinical Isolates Respond to UL29-Targeted siRNA Swarm Treatment Independent of Their Acyclovir Sensitivity

Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the antiviral potential of a UL29 siRNA swarm against circulating strains of HSV-1, in comparison with acyclovir. All circulating strains were sensitive to both antivirals, with the half-maximal inhibitory concentrations (IC50) in the range of 350-1911 nM for acyclovir and 0.5-3 nM for the UL29 siRNA swarm. Additionally, we showed that an acyclovir-resistant HSV-1, devoid of thymidine kinase, is highly sensitive to UL29 siRNA treatment (IC50 1.0 nM; I-max 97%). Moreover, the detected minor variations in the RNAi target of the HSV strains had no effect on the potency or efficacy of UL29 siRNA swarm treatment. Our findings support the development of siRNA swarms for the treatment of HSV-1 infections, in order to circumvent any potential acyclovir resistance

The screens culture: impact on ADHD

Children’s use of electronic media, including Internet and video gaming, has increased dramatically to an average in the general population of roughly 3 h per day. Some children cannot control their Internet use leading to increasing research on “internet addiction.” The objective of this article is to review the research on ADHD as a risk factor for Internet addiction and gaming, its complications, and what research and methodological questions remain to be addressed. The literature search was done in PubMed and Psychinfo, as well as by hand. Previous research has demonstrated rates of Internet addiction as high as 25% in the population and that it is addiction more than time of use that is best correlated with psychopathology. Various studies confirm that psychiatric disorders, and ADHD in particular, are associated with overuse, with severity of ADHD specifically correlated with the amount of use. ADHD children may be vulnerable since these games operate in brief segments that are not attention demanding. In addition, they offer immediate rewards with a strong incentive to increase the reward by trying the next level. The time spent on these games may also exacerbate ADHD symptoms, if not directly then through the loss of time spent on more developmentally challenging tasks. While this is a major issue for many parents, there is no empirical research on effective treatment. Internet and off-line gaming overuse and addiction are serious concerns for ADHD youth. Research is limited by the lack of measures for youth or parents, studies of children at risk, and studies of impact and treatment

Marine Tar Residues: a Review

Abstract Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean envi-ronment indefinitely, decomposing or becoming buried in the sea floor. However, in many cases, they are transported ashore via currents and waves where they pose a concern to coastal recreation activities, the seafood industry and may have negative effects on wildlife. This review summarizes the current state of knowledge on marine tar residue formation, transport, degradation, and distribution. Methods of detection and removal of marine tar residues and their possible ecological effects are discussed, in addition to topics of marine tar research that warrant further investigation. Emphasis is placed on ben-thic tar residues, with a focus on the remnants of the Deepwater Horizon oil spill in particular, which are still affecting the northern Gulf of Mexico shores years after the leaking submarine well was capped

Segmentation of facial bone surfaces by patch growing from cone beam CT volumes

Objectives: The motivation behind this work was to design an automatic algorithm capable of segmenting the exterior of the dental and facial bones including the mandible, teeth, maxilla and zygomatic bone with an open surface (a surface with a boundary) from CBCT images for the anatomy-based reconstruction of radiographs. Such an algorithm would provide speed, consistency and improved image quality for clinical workflows, for example, in planning of implants. Methods: We used CBCT images from two studies: first to develop (n519) and then to test (n530) a segmentation pipeline. The pipeline operates by parameterizing the topology and shape of the target, searching for potential points on the facial bone-soft tissue edge, reconstructing a triangular mesh by growing patches on from the edge points with good contrast and regularizing the result with a surface polynomial. This process is repeated for convergence. Results: The output of the algorithm was benchmarked against a hand-drawn reference and reached a 0.50 ± 1.0-mm average and 1.1-mm root mean squares error in Euclidean distance from the reference to our automatically segmented surface. These results were achieved with images affected by inhomogeneity, noise and metal artefacts that are typical for dental CBCT. Conclusions: Previously, this level of ccuracy and precision in dental CBCT has been reported in segmenting only the mandible, a much easier target. The segmentation results were consistent throughout the data set and the pipeline was found fast enough (,1-min average computation time) to be considered for clinical use

Effects of Pain and Pain Management on Motor Recovery of Spinal Cord-Injured Patients: A Longitudinal Study

BACKGROUND Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. OBJECTIVE The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. METHODS We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. RESULTS A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. CONCLUSION While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI

Electrophysiological Multimodal Assessments Improve Outcome Prediction in Traumatic Cervical Spinal Cord Injury

Item does not contain fulltextOutcome prediction after spinal cord injury (SCI) is essential for early counseling and orientation of the rehabilitative intervention. Moreover, prognostication of outcome is crucial to achieving meaningful stratification when conceiving clinical trials. Neurophysiological examinations are commonly employed for prognostication after SCI, but whether neurophysiology could improve the functional prognosis based on clinical predictors remains an open question. Data of 224 patients included in the European Multicenter Study about Spinal Cord Injury were analyzed with bootstrapping analysis and multivariate logistical regression to derive prediction models of complete functional recovery in the chronic stage after traumatic cervical SCI. Within 40 days after SCI, we evaluated age, gender, the motor and sensory cumulative scores of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), and neurophysiological variables (motor evoked potentials, sensory evoked potentials, nerve conduction study) as possible predictors. Positive outcome was defined by a Spinal Cord Independence Measure total score of 100. Analyzing clinical variables, we derived a prediction model based on the ISNCSCI total motor score and age: the area under the receiver operating curve (AUC) was 0.936 (95% confidence interval [CI]: 0.904-0.968). Adding neurophysiological variables to the model, the AUC increased significantly: 0.956 (95% CI: 0.930-0.982; p = 0.019). More patients could be correctly classified by adding the electrophysiological data. Our study demonstrates that neurophysiological assessment improves the prediction of functional prognosis after traumatic cervical SCI, and suggests the use of neurophysiology to optimize patient information, rehabilitation, and discharge planning and the design of future clinical trials