Peer assessment as a method for measuring harmful internet use.

Harmful Internet use (HIU) describes unintended use of the Internet. It could be both self-harm and harming others. Our research goal is to develop a more accurate method for measuring HIU by this novel peer assessment. As such, it may become, with our call for more research, a paradigm shift supplementing every rating scale or other type of Internet use assessment. In addition to classic statistical analysis, structural equations have been employed. Results indicate that the true positive rate (TPR) is substantially higher than assessed in other studies.•Peer assessment improvement.•AUC for ROC was computed to establish cut-off points for the used scale.•Results obtained by the Structural Equation model indicate that parental care has a moderate influence on subjects' attempts to fight HIU.

Impact of multiple medical interventions on mortality, length of hospital stay and reepithelialization time in Toxic Epidermal Necrolysis, Steven-Johnsons Syndrome, and TEN/SJS Overlap - Metanalysis and metaregression of observational studies.

Stevens-Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis are rare, life-threatening dermatologic conditions with acute onset and not clearly established treatment protocol. A plethora of observational studies are present with lack of up-to-date consensus based on evaluation of objective endpoints, among others mortality. Thorough analysis of available databases (Pubmed, EMBASE, Cinahl, Web of Science, Clinical Trials) was conducted according to PRISMA guidelines. Authors initially identified 700 papers, with 82 of them potentially eligible according to adopted criteria. A total of 42 studies were included into pooled synthesis. For continuous outcomes we analyzed the pooled means for endpoint scores using observed cases data. Categorical outcomes were analyzed by calculating the pooled event rates. We conducted subgroup and exploratory maximum likelihood random effects meta-regression analyses regarding SCORTEN of all outcomes. Using random-effects model, the overall pooled Mortality Rate was 0.191 (95%CI, 0.132-0.269). The lowest mortality rate was found to be linked with Etanercept and highest in Total Plasma Exchange (TPE) and Intravenous Immunoglobulin (IVIG). Overall reepithelization was 13.278 days (95%CI, 8.773-17.784),The highest was found in cyclosporine treatment; 14.739 whilst the lowest for steroids. Length of hospital stay in overall analysis was 19.99 days (95%CI, 16.53-23.44),the highest was linked with TPE/TPE+IvIg treatment, the lowest with steroids. Risk of bias of assessed studies was estimated to be high (for observational studies mean STROBE score 12.44). High quality TEN and SJS studies are lacking. Almost all papers report observational data without randomization and double-blind control. Therefore, the pooled analysis cannot be presented with initial bias. In our meta-analysis the most successful regimen was Etanercept treatment. It was linked with the lowest mortality. The most negative treatment outcome was observed in studies reporting TPE and IVIG. Randomized trials of high quality are needed in SJS and TEN.

Locally abundant, endangered Mariana swiftlets impact the abundance, behavior, and body condition of an invasive predator.

Invasive predators are known to have negative consumptive and non-consumptive effects on native species, but few examples show how the abundance of native prey may influence an established invasive predator. We compared invasive brown treesnakes (Boiga irregularis; BTS) found in caves occupied by endangered Mariana swiftlets (Aerodramus bartschi) to snakes found in nearby forests and caves without birds to quantify how the abundance of native avian prey impacts BTS abundance and behavior on Guam. From 2011 to 2017 we removed 151 BTS in caves occupied by swiftlets and never observed BTS in caves without birds. Notable locations included snakes foraging near swiftlets and in holes that allowed cave access and escape from capture. Of 43 BTS with gut contents, 27 (63%) contained swiftlets. BTS in swiftlet-occupied caves had greater fat mass compared to forests, indicating access to swiftlets may increase body condition and promote reproduction. Number of ovarian follicles was significantly greater in female snakes from swiftlet-occupied caves compared to those from ravine, but not limestone forests; evidence of male BTS being more capable of reproduction was limited (i.e., fewer non-discernible but not significantly larger testes in snakes from caves). Assuming other limiting factors are considered, altering the functional response of predators through the modification of caves or interdiction lures to exclude or hinder the largest BTS could bolster swiftlet populations by increasing nesting refugia in currently-occupied caves and facilitate recolonization of historical caves.

The initial factors affecting in-hospital mortality rate of patients undergoing surgery for post-traumatic extra-axial hematomas.

INTRODUCTION: Traumatic brain injury (TBI) is one of the most important causes of disability and death among young adults and referred to as "silent" epidemic. The most frequent consequences of a TBI are extra-axial hematomas, comprising of acute subdural (SDH) and epidural hematoma (EDH). Most of the factors affecting the mortality have been analyzed in a wide group of TBI. The aim of this study is to identify factors affecting in-hospital mortality in patients undergoing surgery for acute traumatic subdural and epidural hematoma. PATIENTS AND METHODS: The study included 128 patients operated on due to extra-axial hematomas. Twenty-eight patients were operated on for EDH and 100 on for SDH. Patients were treated at the Department of Neurosurgery Medical University in Lublin, during almost three years. The following factors were analyzed: demographic data, physiological factors, laboratory factors, computed tomography scan characteristics and time between the trauma and the surgery. All the factors were correlated with in-hospital mortality rate. RESULTS: The univariate analysis has confirmed the influence of many factors affecting the in-hospital mortality. CONCLUSION: It is interesting that factors such as GSC score, systolic blood pressure, respiratory rate and glycemia were associated with in-hospital mortality rate with highly statistically significant differences (Tab. 3, Fig. 2, Ref. 40).

Effect of confining pressure on diffusion coefficients in clay-rich, low-permeability sedimentary rocks.

The effect of confining pressure (CP) on the diffusion of tritiated-water (HTO) and iodide (I-) tracers through Ordovician rocks from the Michigan Basin, southwestern Ontario, Canada, and Opalinus Clay from Schlattingen, Switzerland was investigated in laboratory experiments. Four samples representing different formations and lithologies in the Michigan Basin were studied: Queenston Formation shale, Georgian Bay Formation shale, Cobourg Formation limestone and Cobourg Formation argillaceous limestone. Estimated in situ vertical stresses at the depths from which the samples were retrieved range from 12.0 to 17.4MPa (Michigan Basin) and from 21 to 23MPa (Opalinus Clay). Effective diffusion coefficients (De) were determined in through-diffusion experiments. With HTO tracer, applying CP resulted in decreases in De of 12.5% for the Queenston Formation shale (CPmax=12MPa), 30% for the Georgian Bay Formation shale (15MPa), 34% for the Cobourg Formation limestone (17.4MPa), 31% for the Cobourg Formation argillaceous limestone (17.4MPa) and 43-46% for the Opalinus Clay (15MPa). Decreases in De were larger for the I- tracer: 13.8% for the Queenston shale, 42% for the Georgian Bay shale, 50% for the Cobourg Formation limestone, 55% for the Cobourg Formation argillaceous limestone and 63-68% for the Opalinus Clay. The tracer-specific nature of the response is attributed to an increasing influence of anion exclusion as the pore size decreases at higher CP. Results from the shales (including Opalinus Clay) indicate that the pressure effect on De can be represented by a linear relationship between De and ln(CP), which provides valuable predictive capability. The nonlinearity results in a relatively small change in De at high CP, suggesting that it is not necessary to apply the exact in situ pressure conditions in order to obtain a good estimate of the in situ diffusion coefficient. Most importantly, the CP effect on shale is reversible (±12%) suggesting that, for argillaceous rocks, it is possible to obtain De values that are representative of the in-situ condition by conducting measurements on re-pressurized samples that were obtained with standard drilling practices. This may not be the case for brittle rock samples as the results from limestone suggest that irreversible damage occurred during the pressure cycling.

Methodological considerations when assessing restricted and repetitive behaviors and aggression.

Methodological issues impacting the relationship between aggression and restricted, repetitive, and stereotyped behaviors and interests (RRSBI) were examined in 2648 children and adolescents with autism spectrum disorders (ASD) using a multi-method, multi-informant analysis model to assess the effects of informant, assessment method, and aggression phenotype. Overall, a significant, but small relationship was found between RRSBI and aggression (p < .05). There was significant heterogeneity of estimates with large effect sizes observed when utilizing teacher report and a broad phenotype of aggression. Variance in estimates was attributed to differences in informant and assessment method with two times greater effect attributed to informant. Results suggest strategies to optimize future investigations of the relationship between RRSBI and aggression. Findings also provide the opportunity for the development of targeted interventions for aggression in youth with ASD.

Dispersion-cancelled biological imaging with quantum-inspired interferometry.

Quantum information science promises transformative impact over a range of key technologies in computing, communication, and sensing. A prominent example uses entangled photons to overcome the resolution-degrading effects of dispersion in the medical-imaging technology, optical coherence tomography. The quantum solution introduces new challenges: inherently low signal and artifacts, additional unwanted signal features. It has recently been shown that entanglement is not a requirement for automatic dispersion cancellation. Such classical techniques could solve the low-signal problem, however they all still suffer from artifacts. Here, we introduce a method of chirped-pulse interferometry based on shaped laser pulses, and use it to produce artifact-free, high-resolution, dispersion-cancelled images of the internal structure of a biological sample. Our work fulfills one of the promises of quantum technologies: automatic-dispersion-cancellation interferometry in biomedical imaging. It also shows how subtle differences between a quantum technique and its classical analogue may have unforeseen, yet beneficial, consequences.

Psychiatric symptoms correlate with metabolic indices in the hippocampus and cingulate in patients with mitochondrial disorders.

There is increasing recognition that mitochondrial dysfunction may have a critical role in the pathophysiology of major psychiatric illnesses. Patients with mitochondrial disorders offer a unique window through which we can begin to understand the association between psychiatric symptoms and mitochondrial dysfunction in vivo. Using proton magnetic resonance spectroscopy ((1)H-MRS), we investigated metabolic indices in mitochondrial patients in regions of the brain that have been implicated in psychiatric illness: the caudate, cingulate cortex and hippocampus. In all, 15 patients with mitochondrial disorders and 15 age- and sex-matched controls underwent a comprehensive psychiatric assessment, including the administration of standardized psychiatric rating scales, followed by single voxel (1)H-MRS of the caudate, cingulate cortex and hippocampus to measure N-acetyl aspartate (NAA), creatine (Cr), glycerophosphocholine (GPC), myoinositol and glutamate+glutamine (Glx). Pearson's correlation coefficients were used to determine correlations between metabolites and the psychiatric rating scales. Anxiety symptoms in these patients correlated with higher GPC, Glx, myoinositol and Cr in the hippocampus. Impaired level of function as a result of psychiatric symptoms correlated with higher Glx and GPC in the cingulate cortex. In summary, we found remarkably consistent, and statistically significant, correlations between anxiety and metabolic indices in the hippocampus in patients with mitochondrial disorders, while overall impairment of functioning due to psychiatric symptoms correlated with metabolic markers in the cingulate cortex. These findings lend support to the notion that mitochondrial dysfunction in specific brain regions can give rise to psychiatric symptoms. In particular, they suggest that metabolic processes in the hippocampus may have an important role in the neurobiology of anxiety.

Sorafenib in hepatocellular carcinoma - a post marketing evaluation.

BACKGROUND: Sorafenib is an orally active multikinase inhibitor licensed for the treatment of patients with unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The web-based registry, used for appraisal on new drugs, allows developing the observational prospective analysis of innovative drug therapies. To establish clinical impact of Sorafenib, institutional data were collected prospectively through the registry. RESULTS: A total of 81 patients treated with Sorafenib were reviewed (median age = 65 years) and the follow-up duration was 30 months. Every patient was checked for length of treatment, toxicity and outcomes. Based on the study sample, the median time to progression was 3 months and median overall survival was 8 months. We found 52% progressions at first evaluation and the disease control rate was 32%. CONCLUSION: Our data from real life practice showed that the clinical benefit of Sorafenib in unresectable HCC was gained in selected responder patients.

Inhibition of the serotonin transporter induces microglial activation and downregulation of dopaminergic neurons in the substantia nigra.

Drugs that selectively inhibit the serotonin transporter (SERT) are widely used in the treatment of depression and anxiety disorders. These agents are associated with a range of extrapyramidal syndromes such as akathisia, dystonia, dyskinesia and parkinsonism, suggesting an effect on dopaminergic transmission. We studied the time course of changes in dopaminergic neurons in the substantia nigra (SN) after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (N = 9) or mixed with citalopram 5 mg/kg/day (N = 27). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of SN were processed for tyrosine hydroxylase (TH) immunohistochemistry. Citalopram induced a significant decrease in TH-positive cell counts at 24 h (44%), 7 days (38%) and 28 days (33%). No significant differences among the citalopram treatment groups were observed in the SN. To determine whether these changes would occur with other SERT inhibitors, we conducted a second experiment, this time with a 28 day course of fluoxetine. As was observed with citalopram, fluoxetine induced a significant 21% reduction of TH cell counts in the SN. Immunoblot analysis showed that fluoxetine also induced a 45% reduction of striatal TH. To investigate a possible role for the innate immune system in mediating these changes, we also studied the microglial marker OX42 after administration of fluoxetine and noted a significant 63% increase in the SN of fluoxtine-treated animals. These results indicate that SERT inhibition can activate microglia and alter the regulation of TH, the rate limiting enzyme for dopamine biosynthesis. These changes may play a role in mediating the extrapyramidal side effects associated with SERT inhibitors.

Role of the dopamine transporter in mediating the neuroleptic-induced reduction of tyrosine hydroxylase-immunoreactive midbrain neurons.

We have previously reported a long-term downregulation of midbrain dopaminergic neurons following treatment with neuroleptic medications. The mechanism of this effect is not clear. The dopamine transporter (DAT) has been shown to play a role in the behavioural and biochemical action of neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We postulated a role for the DAT in mediating the changes induced by neuroleptic (i.e., antipsychotic) drugs. In the first experiment, Sprague-Dawley rats simultaneously received twice daily sub-cutaneous injections of either saline or the DAT inhibitor GBR 12909 (GBR; 5 mg/kg/day) and haloperidol (HAL; 2 mg/kg/day) or vehicle. In the second experiment, the animals were treated with daily sub-cutaneous injections of saline or the DAT inhibitor GBR 129091 plus oral risperidone (RISP; 1.5 mg/kg/day) or vehicle. In a third experiment, animals were given normal drinking water or water with clozapine (CLZ, 20 mg/kg/day). Animals were sacrificed immediately after the last treatment. Sections of the substantia nigra (SN) and ventral tegmental area (VTA) were processed for tyrosine hydroxylase (TH) immunoreactivity. Cell counts were analyzed by one-way analysis of variance followed by post-hoc Tukey tests, with significance set at p<0.05. Treatment with HAL or RISP resulted in a significant reduction (HAL 27%; RISP 25%) in the number of TH-immunoreactive cells present in the medial SN pars compacta. This effect was in both cases completely blocked by administration of the DAT inhibitor. In the VTA, TH-positive cell counts were significantly decreased with RISP, but not with HAL. Once again, the RISP-induced changes were blocked by co-administration of the DAT inhibitor. CLZ treatment did not significantly affect TH-positive cell counts in the SN. These results indicate a role for the active dopamine transporter in mediating the suppression of TH expression in midbrain dopaminergic neurons by antipsychotic drugs. DAT inhibitors may prove useful in ameliorating the neurological side effects of antipsychotic medication.

Role of serotonin transporter inhibition in the regulation of tryptophan hydroxylase in brainstem raphe nuclei: time course and regional specificity.

Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (n=9) or mixed with citalopram 5 mg/kg/day (n=27). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of dorsal raphe nucleus (DRN), median raphe nucleus (MRN), raphe magnus nucleus (RMN) and caudal linear nucleus (CLN) were processed for TPH immunohistochemistry. Citalopram induced a significant reduction in DRN TPH-positive cell counts at 24 h (41%), 7 days (38%) and 28 days (52%). Similar reductions in TPH-positive cell counts were also observed at each timepoint in the MRN and in the RMN. In the MRN, citalopram resulted in significant reductions at 24 h (26%), 7 days (16%) and 28 days (23%). In the RMN, citalopram induced significant reductions of TPH-positive cell counts at 24 h (45%), 7 days (34%) and 28 days (43%). By contrast, no significant differences between control and treatment groups were observed in the CLN at any of the time points that we studied. To investigate whether these changes would occur with other SERT inhibitors, we conducted a second experiment, this time with a 28-day course of fluoxetine. As was observed with citalopram, fluoxetine induced significant reductions of TPH cell counts in the DRN (39%), MRN (38%) and RMN (41%), with no significant differences in the CLN. These results indicate that SERT inhibition can alter the regulation of TPH, the rate limiting enzyme for serotonin biosynthesis. This persistent and regionally specific downregulation of serotonin biosynthesis may account for some of the clinical withdrawal symptoms associated with drugs that inhibit SERT.

Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis.

The purpose of this study was to present a retrospective analysis of the frequency of nontuberculous mycobacteria (NTM)-related pulmonary infections among the AFB-positive and/or culture-positive patients in the Warsaw region who were suspected of tuberculosis (TB) and hospitalized in the university hospital between 1999 and 2005. All the AFB-positive pulmonary samples were examined with a molecular method using the Amplicor MTB test (Roche) for detection of Mycobacterium tuberculosis complex, and all mycobacterial isolates were speciated by high performance liquid chromatography (HPLC) analysis of mycolic acids. Patients who met clinical, radiological, and bacteriological criteria of mycobacteriosis were classified according to the American Thoracic Society (ATS) guidelines for diagnosis of NTM related disease. Among the 445 smear-positive or/and culture-positive patients, 142 subjects (31.9%) were found to be infected with M. tuberculosis. Among 303 non-TB patients, mycobacteriosis was found in 27 (8.9%) subjects. The frequency of NTM-related lung disease as compared to the bacteriologically-confirmed lung TB was estimated at 1:5. The rapid, precise methods of NTM speciation are necessary for progress in diagnostics of NTM related diseases.

Presence of MHC-I in rat glioma cells expressing antisense IGF-I-receptor RNA.

The supposed immunogenic character of glioma cells transfected with antisense IGF-I-Receptor (IGF-I-R) expression vector was tested for the presence of MHC-I currently present in cells of IGF-I antisense type. C6 rat glioma cell line was comparatively transfected in vitro with IGF I antisense (pMT-Anti-IGF I) or IGF I Receptor antisense (pMT-Anti-IGF I R) expression vectors. The wild and transfected cells were examined for the presence of IGF-I and MHC-I molecules. Using RT PCR technique, the transfected "antisens" cells showed total inhibition of IGF-I. The both transfected cultures of IGF-I and of IGF-I-R type were positively stained for MHC-I. Moreover "antisense IGF-I-R" cells as compared to "IGF-I antisense" cells showed slightly higher expression of MHC-I. The transfected cells showed also the feature of apoptosis in 60% of cells. The immunogenicity of IGF-I-R antisense glioma cells is related to MHC-I presence; therefore both approaches of antisense IGF-I and of antisense IGF-I-R could be use in paralel for cellular therapy of glioblastoma.

Limits to the temporal fidelity of cortical spike rate signals.

The cerebral cortex processes information primarily through changes in the spike rates of neurons within local ensembles. To evaluate how reliably the average spike rate of a group of cortical neurons can represent a time-varying signal, we simulated an ensemble with realistic spike discharge behavior. We found that weak interneuronal correlation, or synchrony, allows the variability in spike rates of individual neurons to compromise the ensemble representation of time-varying signals. Brief cycles of sinusoidal modulation at frequencies above 115 Hz could not be represented by an ensemble of hundreds of neurons whose interneuronal correlation mimics that of the visual cortex. The spike variability and correlation assumed in our simulations are likely to apply to many areas of cortex and therefore may constrain the fidelity of neural computations underlying higher brain function.

Amlodipine enhances the activity of antiepileptic drugs against pentylenetetrazole-induced seizures.

Amlodipine (AML), which belongs to the 1,4-dihydropyridine calcium channel antagonists, possesses pharmacological and pharmacokinetic profile that distinguishes it from other agents of this class. Pentylenetetrazole (PTZ)-induced clonic and tonic convulsions in mice were significantly reduced by administration of AML at 10 mg/kg. At this dose AML remained without influence upon the plasma level of PTZ. The ED50 value of AML against clonic seizures induced by PTZ was 5.4 mg/kg. This calcium channel antagonist (at 2.5 mg/kg) combined with ethosuximide (ETX), valproate magnesium (VPA) or phenobarbital (PB) significantly reduced their ED50 values against clonic phase of PTZ-induced seizures. AML administered alone or in combination with antiepileptic drugs (AEDs) worsened the motor performance of mice in the chimney test. However, these treatments remained without significant influence on the retention time in the passive avoidance test. Plasma levels of antiepileptics remained unchanged in the presence of AML. The results indicate that AML does not seem a good candidate for a combination therapy in epileptic patients because of its adverse potential.

Capillary gas chromatography-atomic emission spectroscopy-mass spectrometry analysis of sulphur mustard and transformation products in a block recovered from the Baltic Sea.

A block of yperite fished up from the Baltic Sea was analysed by gas chromatography coupled with atomic emission spectrometry and mass spectrometry. In the samples of the block about 50 compounds were detected, out of which 30 were identified. The identification of the compounds was performed by using the element chromatograms of the investigated compounds, and the data obtained by mass spectrometric detection. Thiodiglycol was not found among the compounds present in the investigated block. The calculations of the contents of sulphur mustard and some products in the block were performed by an external calibration method using bis(2-chloroethyl) sulphide as the standard. A satisfactory precision of elements determinations was obtained (RSD from 4.4 to 14.3%).