AUTOIMMUNE CONCEPT OF SCHIZOPHRENIA: HISTORICAL ROOTS AND CURRENT FACETS

Background: The review analyzes the possible role of autoimmune processes in the pathogenesis of schizophrenia and the evolution of concepts on this issue from its origin to the present. Results: Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens’ effects, stress and infections with various pathogens at different stages of ontogenesis. An increase in the levels of proinflammatory cytokines and chemokines as well as a decrease in the levels of anti-inflammatory ones also may contribute to schizophrenia risks. Schizophrenia often occurs in those patients having various autoimmune diseases and their first-degree relatives. Conclusion: Cases of schizophrenia resulted from autoimmune pathogenesis (including autoimmune encephalitis caused by autoantibodies against various neuronal antigens) are characterized by quite severe cognitive and psychotic symptoms and a less favorable prognosis. This severe course may result from the chronic immune damage of the neuronal receptors such as NMDA, GABA, and others and depend on hyperprolactinemia, induced by antipsychotics, but aggravating autoimmune processes

Timing and Dose of Upper Limb Motor Intervention After Stroke: A Systematic Review

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22–66) and study sample size remains small (median n=30, IQR 20–48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1–7 days), 176 early subacute (8–90 days), 34 late subacute (91–180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600–1430) min/session, 1 (IQR, 1–1) session/d, 5 (IQR, 5–5) d/wk for 4 (IQR, 3–5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629

One-loop Quantum Gravity in Schwarzschild Spacetime

The quantum theory of linearized perturbations of the gravitational field of a Schwarzschild black hole is presented. The fundamental operators are seen to be the perturbed Weyl scalars $\dot\Psi_0$ and $\dot\Psi_4$ associated with the Newman-Penrose description of the classical theory. Formulae are obtained for the expectation values of the modulus squared of these operators in the Boulware, Unruh and Hartle-Hawking quantum states. Differences between the renormalized expectation values of both $\bigl| \dot\Psi_0 \bigr|^2$ and $\bigl| \dot\Psi_4 \bigr|^2$ in the three quantum states are evaluated numerically.Comment: 39 pages, 11 Postscript figures, using revte

Piezo-Optical Transducers in High Sensitive Strain Measurements

New piezo-optical sensors based on the piezo-optical effect for high sensitive mechanical stress measurements have been proposed and developed. The piezo-optical method provides the highest sensitivity to strains compared to sensors based on any other physical principles. Piezo-optical sensors use materials whose parameters practically not change under load or over time, therefore piezo-optical sensors are devoid of the disadvantages inherent in strain-resistive and piezoelectric sensors, such as hysteresis, parameters degradation with time, small dynamic range, low sensitivity to strains, and high sensitivity to overloads. Accurate numerical simulation and experimental investigations of the piezo-optical transducer output signal formation made it possible to optimize its design and show that the its gauge factor is two to three orders of magnitude higher than the gauge factors of sensors of other types. The cruciform shape of the transducer photoelastic element made it possible to significantly increase the stresses in its working area at a given external force. Combining compactness, reliability, resistance to overloads, linearity and high sensitivity, in terms of the all set of these parameters, piezo-optical sensors significantly surpass the currently widely used strain-resistive, piezoelectric and fiber-optic sensors and open up new, previously inaccessible, possibilities in the tasks of measuring power loads

UTA versus line emission for EUVL: Studies on xenon emission at the NIST EBIT

Spectra from xenon ions have been recorded at the NIST EBIT and the emission into a 2% bandwidth at 13.5 nm arising from 4d-5p transitions compared with that from 4d-4f and 4p-4d transitions in Xe XI and also with that obtained from the unresolved transition array (UTA) observed to peak just below 11 nm. It was found that an improvement of a factor of five could be gained in photon yield using the UTA rather than the 4d-5p emission. The results are compared with atomic structure calculations and imply that a significant gain in efficiency should be obtained using tin, in which the emission at 13.5 nm comes from a similar UTA, rather than xenon as an EUVL source material

Influence of silicone mammoplasty on the immunoendocrine status of female recipients

The article concerns a study of early influence of silicone breast implants on the development of autoimmune reactions and dynamics of prolactin and thyroid hormone levels in women after mammoplasty. At the present time, this issue remains relevant for several reasons: more than 20 million pairs of implants have been installed in the world and the number of their implantations is constantly growing. Despite relative safety of the silicone implants, some of them are periodically banned by regulatory bodies in various countries. At the same time, there is a growing number of controversial publications in the scientific literature, about potential adverse consequences of their use. Some authors suggest an association between the silicone implants and risk of developing autoimmune conditions, connective tissue disorders, and occasional malignancies. On the other hand, the journals are full of publications about the overall safe tolerance of such medical devices by the patients. These considerations served as a pre-requisite to our research. As part of this project, we have assayed serum levels of autoantibodies to ten antigens, as well as contents of prolactin and thyroid hormones by means of ELISA technique in 27 patients before, 3 and 6 months after aesthetic and reconstructive mammoplastics performed within a period of September 2018 to November 2019. As a result, it was found that 5 out of 27 patients exhibited changes in the autoimmunity spectrum and intensity after mammoplasty. In particular, the concentrations of autoantibodies to modified citrullinated vimentin and IgM autoantibodies to cardiolipin exceeded the normal level at 3 and 6 months. In addition, the initially high prolactin concentration in mammoplasty recipients dropped to normal ranges by 3 months after breast surgery, even after several-fold increased initial levels. As for thyroid hormones, there were no statistically significant changes in their dynamics. The increase of autoantibodies to various target antigens after mammoplasty was statistically significant and positively correlated with each other. This can be explained, for example, by dependence on the adjuvant effect of silicone, which is not associated with antigen specificity. However, it may generally stimulate the immune responses

Upright activity and higher motor function may preserve bone mineral density within 6 months of stroke: a longitudinal study

2017-2018 > Academic research: refereed > Publication in refereed journal201807 bcrcVersion of RecordOthersAustralian Research Council (ARCFT09901086), Austin Health Medical Research Fund and La Trobe University Faculty Research Grant.PublishedC

Tenecteplase versus Alteplase before thrombectomy for ischemic stroke

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [&lt;1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

Methodology for generating a global forest management layer

The first ever global map of forest management was generated based on remote sensing data. To collect training data, we launched a series of Geo-Wiki (https://www.geo-wiki.org/) campaigns involving forest experts from different world regions, to explore which information related to forest management could be collected by visual interpretation of very high-resolution images from Google Maps and Microsoft Bing, Sentinel time series and normalized difference vegetation index (NDVI) profiles derived from Google Earth Engine. A machine learning technique was then used with the visually interpreted sample (280K locations) as a training dataset to classify PROBA-V satellite imagery. Finally, we obtained a global wall-to-wall map of forest management at a 100m resolution for the year 2015. The map includes classes such as intact forests; forests with signs of management, including logging; planted forests; woody plantations with a rotation period up to 15 years; oil palm plantations; and agroforestry. The map can be used to deliver further information about forest ecosystems, protected and observed forest status changes, biodiversity assessments, and other ecosystem-related aspects