Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including ...non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.
Addition of deep hyperthermia to radiotherapy results in improved local control (LC) and overall survival compared to radiotherapy alone in cervical carcinoma patients. Based on preclinical data, the ...time interval between radiotherapy, and hyperthermia is expected to influence treatment outcome. Clinical studies addressing the effect of time interval are sparse. The repercussions for clinical applications are substantial, as the time between radiotherapy and hyperthermia should be kept as short as possible. In this study, we therefore investigated the effect of the time interval between radiotherapy and hyperthermia on treatment outcome.
We analyzed all primary cervical carcinoma patients treated between 1996 and 2016 with thermoradiotherapy at our institute. Data on patients, tumors and treatments were collected, including the thermal dose parameters TRISE and CEM43T90. Follow-up data on tumor status and survival as well as late toxicity were collected. Data was analyzed using Cox proportional hazards analysis and Kaplan Meier analysis.
400 patients were included. Kaplan Meier and univariate Cox analysis showed no effect of the time interval (range 30-230 min) on any clinical outcome measure. Besides known prognostic factors, thermal dose parameters TRISE and CEM43T90 had a significant effect on LC. In multivariate analysis, the thermal dose parameter TRISE (HR 0.649; 95% CI 0.501-0.840) and the use of image guided brachytherapy (HR 0.432; 95% CI 0.214-0.972), but not the time interval, were significant predictors of LC and disease specific survival.
The time interval between radiotherapy and hyperthermia, up to 4 h, has no effect on clinical outcome. These results are re-ensuring for our current practice of delivering hyperthermia within maximal 4 h after radiotherapy.
This paper applies the relatively new method of latent transition analysis within the mobility biographies framework to assess how life events influence changes in travel behaviour. Using transition ...analysis, it is assessed how people switch between different travel patterns over time. Data from the first three waves of the Netherlands Mobility Panel (MPN) are used to reveal different travel patterns and analyse transitions between these patterns over time. Six different meaningful travel patterns are revealed. Four exogenous variables and six life events within the household, employment and residential biography are included to assess their effects on people’s transitions between the travel patterns over time. For all life events significant effects are found, indicating that there might indeed be ‘windows of opportunity’ to change travel behaviour when a life event occurs. The results show that, on average, people who only use a single mode are less likely to change their travel pattern compared to multimodal travellers. In addition, the effects of life events and exogenous variables depend on the initial travel pattern. In general, single-mode travellers are less affected by life events than multimodal travellers. This indicates that it is important to include past travel behaviour within mobility biographies studies.
•E-bike ownership in the Netherlands strongly reduces conventional bicycle use, but also car and public transport use.•E-bike ownership is negatively associated conventional bicycle ownership, but ...not with car ownership.•Car owners are more willing to use the e-bike as an alternative compared to the conventional bicycle or public transport.•E-bike ownership has a generative effect on the total distance travelled.
After Asian countries, the e-bike is now also on the rise in many Western countries. Related to this development, an important question posed by scholars is to what extent the adoption of the e-bike will lead to environmental and health benefits. These will be present if the e-bike replaces travel by motorized modes. Surveying the literature addressing this issue, empirical studies conducted to date do indeed reach the conclusion that the e-bike is substituting travel by car. However, a general shortcoming of empirical studies is that substitution is assessed by asking direct questions to e-bike owners. The aim of the present study is to address this limitation and statistically assess the effect of e-bike ownership on various indicators of travel behavior. To this end, a conceptual model is developed, which is specified as a structural equation model and estimated using data from the last three national mobility surveys in the Netherlands (2013, 2014 and 2015). The results show that e-bike ownership strongly reduces the use of the conventional bicycle, but also, to a lesser extent, car and public transport use. Secondly, e-bike owners reduce their car and public transport use more than conventional bicycle owners. And thirdly, on the level of vehicle ownership, the e-bike acts as a substitute for the conventional bicycle and does not act as a substitute for the car. Overall, the results shed some light on the health and environmental benefits of the uptake of e-bikes in the Netherlands.
Plasma-Stimulated Wound Healing Tipa, R. S.; Kroesen, G. M. W.
IEEE transactions on plasma science,
2011-Nov., 2011-11-00, 20111101, Volume:
39, Issue:
11
Journal Article
Peer reviewed
Cold plasma treatment of wounds is gaining much interest, because it will offer a noncontact, painless, and harmless therapy to manage large-area lesions (burn wounds and chronic ulcerations). One of ...the important issues in plasma wound healing is the safety of the method. In this paper, we study in vitro the effects of plasma treatment on cell death, proliferation, and wound healing. We performed a parametric study of plasma-treated 3T3 fibroblast cells. For the treatment, a cold atmospheric plasma needle (13.56-MHz microjet in helium) was used. Cells were cultured in six well plates and subsequently deposited on the bottom of the well. As a wound model, a scratch was made in the cell culture. Then, the proliferation of the cells from the sidewalls into the scratch was observed by microscopy. It appeared that plasma treatment stimulates the proliferation of cells into the scratch. This suggests that plasma treatment could result in accelerated wound healing.
CpG oligonucleotides are short single-stranded synthetic DNA molecules. Upon binding to Toll-like receptor 9 (TLR9), CpG activates immune cells in humans and mice. This results in robust Th1 type ...immunity potentially resulting in clearance of pathogens, reduction of allergy and anti-tumor immunity. However, the effectiveness of CpG as an adjuvant depends on its administration route, with only strong effects seen when CpG is administered locally. As local administration is not always feasible, we generated conjugates to specifically deliver CpG to myeloid cells often abundantly present in tumors. For this we coupled CpG (3′-Thiol-modified phosphorothioate (PTO) CpG-ODN1826 type B (5′-tccatgacgttcctgacgtt-3′)) to monoclonal antibodies (mAbs) directed against the myeloid cell marker CD11b using maleimide-thiol coupling. The CD11b-CpG mAb (αCD11b-CpG) conjugates contained about four CpG molecules/conjugate and displayed binding and internalization characteristics similar to unconjugated CD11b mAbs (αCD11b). The αCD11b-CpG conjugates readily induced maturation of murine dendritic cells (DCs) in a TLR9-dependent manner in vitro. Following intravenous injection, αCD11b-CpG conjugates efficiently targeted CD11b+ immune cells in the blood, lymph nodes and spleen. Finally, injection of αCD11b-CpG conjugates, but not untargeted conjugates, induced maturation of CD11b+ cell subsets in vivo. In conclusion, conjugating CpG to αCD11b enabled specific targeting and activation of myeloid cells in vivo.
Display omitted
•CpG oligonucleotides can be efficiently coupled to anti-CD11b antibodies.•Anti-CD11b-CpG antibody conjugates are readily internalized by CD11b+ myeloid cells.•Delivery of CpG via antibody-conjugates potently activates myeloid cells via TLR9.•Anti-CD11b-CpG conjugates target and activate CD11b+ myeloid cell subsets in vivo.
The borderline between virulence and efficacy in live attenuated vaccine strains is often blurred and this is also the case for the Bacillus Calmette-Guérin (BCG), the only currently licensed ...anti-tuberculosis vaccine used on a large, global scale, which was obtained almost 100 years ago. While BCG is more than 99% identical at the genome level to
Mycobacterium tuberculosis, the causative pathogen of human tuberculosis, some important differences in virulence factors cause naturally irreversible attenuation and safety of this vaccine in the immunocompetent host. Some of these virulence factors are involved in persistence capacities of the vaccine strains and also represent strong immunogens, responsible for inducing different host signaling pathways, which have to be taken into consideration for the development of revised and new vaccine strains. Here we discuss a number of selected mycobacterial features in relation to their biological functions and potential impact on virulence and vaccine efficacy.
PDF
