Penicillin-Induced Epileptiform Ecog Activity in Gerbils: Effects of Physical Exercise and a Diospyros Kaki Extract

Mongolian gerbils (28 males) were divided into four groups, control (C), treadmill-exercised (Ex), treated with the extract of Diospyros kaki (Dk), and treated with the Dk extract plus exercised (Ex+Dk) groups. Animals of the respective groups were running-exercised for 30 min per day during 8 weeks, and the Dk extract (dose 20mg/kg) was given by gavage during five days per week within the same period. After the treatment and exercise period, an epilepsy model was produced by penicillin G injection (500 IU) into the left somatomotor cortex, and electrocorticogram (ECoG) was recorded during 120 min. The mean frequency of spike/wave complexes was significantly smaller in the Ex and Ex+Dk groups from the 65th min of the observation period and, in the Dk group, from the 75th min than the respective value in the C group (P < 0.01, P < 0.05, and P < 0.01, respectively). The differences in the amplitude values and latency to onset of the spike/wave events among all groups usally did not reach the significance level (P > 0.05), but, visin late stages of the observation period, an antiseisure effect of the Dk extract was obvious. Thus, both the running exercise and Dk extract applications inhibit penicillin-induced epileptiform activity by altering the spike/ wave frequency or severity of seizures observed in ECoG recordings. Further studies are needed to determine the effects of physical activity of different intensities and forms and to analyze the active compounds in the Dk extract.Монгольські піщанки (28 самців) були поділені на чотири групи – контрольну (C), піддану тренуванню на тредбані (Ex), групу з уведенням екстракту Diospyros kaki (східної хурми, група Dk) та групу з уведенням вказаного екстракту, комбінованим із тренуванням (Ex+Dk). Тварин відповідних груп тренували, примушуючи бігати 30 хв на день протягом восьми тижнів; екстракт Dk (20 мг/кг) уводився перорально п’ять днів на тиждень протягом того самого періоду. Після періоду тренування та введення екстракту у щурів індукували модельну епілепсію за допомогою ін’єкції 500 МО пеніциліну G у ліву соматомоторну кору і відводили електрокортикограму (ЕКоГ) протягом 20 хв. У групах Ex та Ex+Dk середня частота виникнення комплексів пік/хвиля була вірогідно меншою, ніж у контролі, починаючи з 65-ї хв періоду спостереження; те саме відмічалося в групі Dk починаючи з 75-ї хв вказаного періоду (P < 0.01, P < 0.05 та P < 0.01 відповідно). Відмінності значень амплітуди ЕКоГ та латентного періоду до появи комплексів пік/хвиля в усіх групах звичайно не досягали рівня вірогідності (P > 0.05), але на пізній ділянці періоду спостереження антисудомний вплив екстракту Dk був очевидним. Отже, тренування бігом та уведення екстракту хурми східної пригнічує індуковану пеніциліном епілептиформну активність, змінюючи частоту комплексів пік/хвиля та інтенсивність судомної активності, що спостерігається в ЕКоГ. Потрібні подальші дослідження для того, щоб визначити ефекти фізичної активності різної інтенсивності та форми та проаналізувати активні компоненти екстракту хурми

Cytokine Plasma Levels: Reliable Predictors for Radiation Pneumonitis?

BACKGROUND: Radiotherapy (RT) is the primary treatment modality for inoperable, locally advanced non-small-cell lung cancer (NSCLC), but even with highly conformal treatment planning, radiation pneumonitis (RP) remains the most serious, dose-limiting complication. Previous clinical reports proposed that cytokine plasma levels measured during RT allow to estimate the individual risk of patients to develop RP. The identification of such cytokine risk profiles would facilitate tailoring radiotherapy to maximize treatment efficacy and to minimize radiation toxicity. However, cytokines are produced not only in normal lung tissue after irradiation, but are also over-expressed in tumour cells of NSCLC specimens. This tumour-derived cytokine production may influence circulating plasma levels in NSCLC patients. The aim of the present study was to investigate the prognostic value of TNF-alpha, IL-1beta, IL-6 and TGF-beta1 plasma levels to predict radiation pneumonitis and to evaluate the impact of tumour-derived cytokine production on circulating plasma levels in patients irradiated for NSCLC. METHODOLOGY/PRINCIPAL FINDINGS: In 52 NSCLC patients (stage I-III) cytokine plasma levels were investigated by ELISA before and weekly during RT, during follow-up (1/3/6/9 months after RT), and at the onset of RP. Tumour biopsies were immunohistochemically stained for IL-6 and TGF-beta1, and immunoreactivity was quantified (grade 1-4). RP was evaluated according to LENT-SOMA scale. Tumour response was assessed according to RECIST criteria by chest-CT during follow-up. In our clinical study 21 out of 52 patients developed RP (grade I/II/III/IV: 11/3/6/1 patients). Unexpectedly, cytokine plasma levels measured before and during RT did not correlate with RP incidence. In most patients IL-6 and TGF-beta1 plasma levels were already elevated before RT and correlated significantly with the IL-6 and TGF-beta1 production in corresponding tumour biopsies. Moreover, IL-6 and TGF-beta1 plasma levels measured during follow-up were significantly associated with the individual tumour responses of these patients. CONCLUSIONS/SIGNIFICANCE: The results of this study did not confirm that cytokine plasma levels, neither their absolute nor any relative values, may identify patients at risk for RP. In contrast, the clear correlations of IL-6 and TGF-beta1 plasma levels with the cytokine production in corresponding tumour biopsies and with the individual tumour responses suggest that the tumour is the major source of circulating cytokines in patients receiving RT for advanced NSCLC

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Background We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. Methods We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. Results The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. Conclusion Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.International Carbon Black Associatio

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Oxidative stress response to different exercise intensity with an automated assay: thiol/disulphide homeostasis

PMID = 3140914

Development of a novel high-temperature al alloy for laser powder bed fusion

The number of available materials for Laser Powder Bed Fusion is still limited due to the poor processability of many standard alloys. In particular, the lack of high-strength aluminium alloys, widely used in aerospace and automotive industries, remains a big issue for the spread of beam-based additive manufacturing technologies. In this study, a novel high-strength aluminium alloy for high temperature applications having good processability was developed. The design of the alloy was done based on the chemical composition of the widely used EN AW2618. This Al-Cu-Mg-Ni-Fe alloy was modified with Ti and B in order to promote the formation of TiB2 nuclei in the liquid phase able to stimulate heterogeneous nucleation of grains and to decrease the hot cracking susceptibility of the material. The new Al alloy was manufactured by gas atomisation and processed by Laser Powder Bed Fusion. Samples produced with optimised parameters featured relative density of 99.91%, with no solidification cracks within their microstructure. After aging, the material revealed upper yield strength and ultimate tensile strength of 495 MPa and 460 MPa, respectively. In addition, the alloy showed tensile strength higher than wrought EN AW 2618 at elevated temperatures

De Ritis ratio and biochemical parameters in COVID-19 patients

PMID = 3268388

Modeling and control of a spherical rolling robot: a decoupled dynamics approach

This paper presents the results of a study on the dynamical modeling, analysis, and control of a spherical rolling robot. The rolling mechanism consists of a 2-DOF pendulum located inside a spherical shell with freedom to rotate about the transverse and longitudinal axis. The kinematics of the model has been investigated through the classical methods with rotation matrices. Dynamic modeling of the system is based on the Euler–Lagrange formalism. Nonholonomic and highly nonlinear equations of motion have then been decomposed into two simpler subsystems through the decoupled dynamics approach. A feedback linearization loop with fuzzy controllers has been designed for the control of the decoupled dynamics. Rolling of the controlled mechanism over linear and curvilinear trajectories has been simulated by using the proposed decoupled dynamical model and feedback controllers. Analysis of radius of curvature over curvilinear trajectories has also been investigated.status: publishe