Difficulty of elderly SCI subjects to translate motor recovery -"body function"- into activity of daily living

The objective of this retrospective analysis was to determine whether outcome of body functions and activities as well as length of stay of inpatient rehabilitation is related to age in patients with traumatic spinal cord injury (SCI). Data were collected from a European network of 17 SCI rehabilitation centers (EM-SCI) and 237 traumatic SCI subjects were included. Assessments were performed at one, six and twelve months after SCI. The measures analyzed were: motor score according to the American Spinal Injury Association, Spinal Cord Independence Measure (SCIM), gait speed and length of stay. Correlation analysis was applied to quantify the association between age and change in the outcome measures. A positive relationship was found between age and neurological recovery in both the first and second 6 month- period of assessment. A negative relationship was found between age and change in SCIM in the second six month period after SCI. A negative relationship between age and gait speed was observed in the first half year. Length of stay was not associated with age. It is concluded that age is an important determining factor for functional outcome after SCI and that elderly patients have difficulties in translating an improvement in neurological outcome into functional changes. Therefore, rehabilitation approaches should focus on functional training in elderly subjects

Эвакуация населения при чрезвычайных ситуациях

В результате аварии на Чернобыльской АЭС (1986 г.) радиационное загрязнение затронуло все страны Северного полушария. На опасно загрязненных территориях оказалось более 1 млн. чел. В ряду поколений число смертельных онкологических заболеваний может составить десятки тысяч человек.As a result of the Chernobyl accident (1986), all countries of the Northern Hemisphere were affected by radiation pollution. In dangerously contaminated areas was more than 1 million people. In a number of generations, the number of deadly cancer can amount to tens of thousands of people

Colour vision deficiencies in Alzheimer's disease

Objective: visual disorders are among the earliest symptoms of Alzheimer's disease. It is, however, still controversial as to whether Alzheimer's disease impairs colour vision. In this study, colour vision of Alzheimer's disease patients was tested using the Ishihara test and the PV‐16 choice test. The latter test, primarily designed for children, was chosen in order to avoid problems due to cognitive decline. Methods: 26 patients with mild to severe Alzheimer's disease (M:F=5:21; mean age: 80±9 years, range: 53-95 years) and 25 controls (M:F=5:20; mean age 80±10 years, range: 56-100 years) were rated after undergoing complete neuro‐ophthalmologic examination. Results: the Alzheimer's disease patients made significantly more unspecific errors in the Ishihara test (P=0.02) and in the PV‐16 choice test (P=0.0008) than the controls. No relation between test performance and severity of Alzheimer's disease was found. Conclusions: Alzheimer's disease patients have an unspecific colour vision deficiency independent of the severity of the diseas

Synthesis and Metabolism of Drugs by Means of Enzyme-Catalysed Reactions

The usefulness of enzyme catalysed-reactions is exemplified by recent results from research at Roche.Sequences of enzyme reactions, well organised in metabolic pathways of selected microorganisms, lead to secondary metabolites with innovative chemical structures. An example is the pancreas-lipase inhibitor lipstatin produced by Streptomyces toxytricini. Hydrogenation of lipstatin yields tetrahydrolipstatin, the active substance of the anti-obesity drug Xenical™. The biosynthetic pathway has been elucidated and an improved fermentation process for the production of lipstatin has been developed.Intermediates of the primary metabolism can be valuable building blocks for the chemical synthesis of drugs. Examples are quinic acid and shikimic acid, which are both suitable starting materials for the synthesis of the neuraminidase inhibitor GS 4104. Metabolic engineering of Escherichia coli with the goal to overproduce these two substances is briefly described.Microorganisms or enzymes derived thereof are used in drug synthesis to catalyse single, highly specific reaction steps (biotransformations). Three examples yielding chiral precursors of a protein-kinase inhibitor, a collagenase inhibitor, and an antifungal compound are discussed.Recombinant Escherichia coli strains expressing human drug-metabolising enzymes are suited to mimic drug metabolism and to produce intermediates of human drug metabolism. The desired hydroxylated drug derivatives could be obtained after incubation of drug substances with strains coexpressing one specific human cytochrome P450 isozyme together with human reductase

Bright light therapy in pregnant women with major depressive disorder: Study protocol for a randomized, double-blind, controlled clinical trial

Background: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. Methods: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. Discussion: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Trial registration: Netherlands Trial Register NTR5476. Registered 5 November 2015

Characterization of young and aged ferrets as animal models for SARS-CoV-2 infection with focus on neutrophil extracellular traps

Neutrophil extracellular traps (NETs) are net-like structures released by activated neutrophils upon infection [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] as part of the innate immune response that have protective effects by pathogen entrapment and immobilization or result in detrimental consequences for the host due to the massive release of NETs and their impaired degradation by nucleases like DNase-1. Higher amounts of NETs are associated with coronavirus disease 2019 (COVID-19) severity and are a risk factor for severe disease outcome. The objective of our study was to investigate NET formation in young versus aged ferrets to evaluate their value as translational model for SARS-CoV-2-infection and to correlate different NET markers and virological parameters. In each of the two groups (young and aged), nine female ferrets were intratracheally infected with 1 mL of 106 TCID50/mL SARS-CoV-2 (BavPat1/2020) and euthanized at 4, 7, or 21 days post-infection. Three animals per group served as negative controls. Significantly more infectious virus and viral RNA was found in the upper respiratory tract of aged ferrets. Interestingly, cell-free DNA and DNase-1 activity was generally higher in bronchoalveolar lavage fluid (BALF) but significantly lower in serum of aged compared to young ferrets. In accordance with these data, immunofluorescence microscopy revealed significantly more NETs in lungs of aged compared to young infected ferrets. The association of SARS-CoV-2-antigen in the respiratory mucosa and NET markers in the nasal conchae, but the absence of virus antigen in the lungs, confirms the nasal epithelium as the major location for virus replication as described for young ferrets. Furthermore, a strong positive correlation was found between virus shedding and cell-free DNA or the level of DNAse-1 activity in aged ferrets. Despite the increased NET formation in infected lungs of aged ferrets, the animals did not show a strong NET phenotype and correlation among tested NET markers. Therefore, ferrets are of limited use to study SARS-CoV-2 pathogenesis associated with NET formation. Nevertheless, the mild to moderate clinical signs, virus shedding pattern, and the lung pathology of aged ferrets confirm those animals as a relevant model to study age-dependent COVID-19 pathogenesis

Digital Extraction Column: Measurement and Modeling Techniques

The digitization of extraction columns requires a profound knowledge of the present hydrodynamics/mass transport interaction as well as appropriate measurement techniques for the detection of relevant input and target values. In this article, the different techniques for droplet size distribution as well as concentration determination are presented and new methods for online evaluation are discussed. In combination with the simulation of droplet size, holdup and solute concentration distribution, an online-capable process tool for controlling and optimizing extraction columns will be obtained

Human rhinoviruses enter and induce proliferation of B lymphocytes

Background: Human rhinoviruses (HRVs) are one of the main causes of virus-induced asthma exacerbations. Infiltration of B lymphocytes into the subepithelial tissue of the lungs has been demonstrated during rhinovirus infection in allergic individuals. However, the mechanisms through which HRVs modulate the immune responses of monocytes and lymphocytes are not yet well described. Objective: To study the dynamics of virus uptake by monocytes and lymphocytes, and the ability of HRVs to induce the activation of in vitro-cultured human peripheral blood mononuclear cells. Methods: Flow cytometry was used for the enumeration and characterization of lymphocytes. Proliferation was estimated using 3H-thymidine or CFSE labeling and ICAM-1 blocking. We used bead-based multiplex assays and quantitative PCR for cytokine quantification. HRV accumulation and replication inside the B lymphocytes was detected by a combination of in situ hybridization (ISH), immunofluorescence, and PCR for positive-strand and negative-strand viral RNA. Cell images were acquired with imaging flow cytometry. Results: By means of imaging flow cytometry, we demonstrate a strong and quick binding of HRV types 16 and 1B to monocytes, and slower interaction of these HRVs with CD4+ T cells, CD8+ T cells, and CD19+ B cells. Importantly, we show that HRVs induce the proliferation of B cells, while the addition of anti-ICAM-1 antibody partially reduces this proliferation for HRV16. We prove with ISH that HRVs can enter B cells, form their viral replication centers, and the newly formed virions are able to infect HeLa cells. In addition, we demonstrate that similar to epithelial cells, HRVs induce the production of pro-inflammatory cytokines in PBMCs. Conclusion: Our results demonstrate for the first time that HRVs enter and form viral replication centers in B lymphocytes and induce the proliferation of B cells. Newly formed virions have the capacity to infect other cells (HeLa). These findings indicate that the regulation of human rhinovirus-induced B-cell responses could be a novel approach to develop therapeutics to treat the virus-induced exacerbation of asthma.</p

Magnetically Shielded Miniature Hall Thruster: Design Improvement and Performance Analysis

ABSTRACT: Magnetic shielding has been shown to dramatically reduce discharge channel wall erosion of high powered Hall thrusters, thereby increasing their useful lifetimes. However, unique challenges exist for developing a low power magnetically shielded Hall thruster. A previously tested 4 cm magnetically shielded miniature Hall thruster demonstrated low performance of its magnetic circuit, resulting in an asymmetric field topology, low thrust, and low efficiency. A 6 cm magnetically shielded Hall thruster was developed to improve upon the 4 cm design. The 6 cm device, which generated a symmetric and fully shielded field topology, was tested at 30 operating conditions ranging from 160 W to nearly 750 W. Visual observation of the plasma and discharge channel during and after operation was used to assess the level of magnetic shielding that was achieved. Hall2De plasma simulations were also used to offer further evidence of magnetic shielding. Thrust stand measurements provided thrust, anode specific impulse, and anode efficiency data at each operating condition. Pole face erosion, which is believed to be associated with the 6 cm thruster&apos;s non-optimized magnetic shielding field topology and strength, identify the near-term challenges to resolve before long lifetimes and high efficiencies can be achieved in low power Hall thrusters