•Reproducibility/Stability of MANIV-DIBH is non-inferior to surface-guided DIBH.•A better cardiopulmonary protection is achieved with mechanical ventilation.•Comfort and treatment time with MANIV are ...similar to surface-guided DIBH.•MANIV enables better inter-fraction heart repositioning.
Deep inspiration breath-hold (DIBH) protects critical organs-at-risk (OARs) for adjuvant breast radiotherapy. Guidance systems e.g. surface guided radiation therapy (SGRT) improve the positional breast reproducibility and stability during DIBH. In parallel, OARs sparing with DIBH is enhanced through different techniques e.g. prone position, continuous positive airway pressure (CPAP). By inducing repeated DIBH with the same level of positive pressure, mechanically-assisted and non-invasive ventilation (MANIV) could potentially combine these DIBH optimizations.
We conducted a randomized, open-label, multicenter and single-institution non-inferiority trial. Sixty-six patients eligible for adjuvant left whole-breast radiotherapy in supine position were equally assigned between mechanically-induced DIBH (MANIV-DIBH) and voluntary DIBH guided by SGRT (sDIBH). The co-primary endpoints were positional breast stability and reproducibility with a non-inferiority margin of 1 mm. Secondary endpoints were tolerance assessed daily via validated scales, treatment time, dose to OARs and their inter-fraction positional reproducibility.
Differences between both arms for positional breast reproducibility and stability occurred at a sub-millimetric level (p < 0.001 for non-inferiority). The left anterior descending artery near-max dose (14,6 ± 12,0 Gy vs. 7,7 ± 7,1 Gy, p = 0,018) and mean dose (5,0 ± 3,5 Gy vs. 3,0 ± 2,0 Gy, p = 0,009) were improved with MANIV-DIBH. The same applied for the V5Gy of the left ventricle (2,4 ± 4,1 % vs. 0,8 ± 1,6 %, p = 0,001) as well as for the left lung V20Gy (11,4 ± 2,8 % vs. 9,7 ± 2,7 %, p = 0,019) and V30Gy (8,0 ± 2,6 % vs. 6,5 ± 2,3 %, p = 0,0018). Better heart’s inter-fraction positional reproducibility was observed with MANIV-DIBH. Tolerance and treatment time were similar.
Mechanical ventilation provides the same target irradiation accuracy as with SGRT while better protecting and repositioning OARs.
The mammalian organism is continuously exposed to various biological and chemical threats from its surroundings. In order to provide protection against these threats, mammals have developed a ...specialized defense system at the interface with their environment. This system, known as the epidermis, is mainly composed of stratified keratinocytes organized in a complex self-renewing structure providing a mechanical and chemical barrier at the skin surface. However, numerous skin-related pathologies can interfere with the proper formation and function of the epidermal barrier. The pathogenesis of these alterations is often very complex. Understanding the changes induced in epidermal tissues by these pathologies at a molecular level is key for their treatment and prevention. In this context, this work aims at developing a thorough and reproducible characterization methodology of the human epidermis by applying ToF-SIMS to the study of an in vitro epidermal model known as reconstructed human epidermis (RHE). Indeed, although the potential of ToF-SIMS for the characterization of the mammalian skin has already been demonstrated, very few studies focus their efforts on the human epidermis itself. Here, we performed static ToF-SIMS characterizations of RHE cryosections, combining both high mass and high lateral resolution acquisitions. In addition, principal components analysis was used as a multivariate analysis tool. This contributed to the decorrelation of the complex datasets obtained from these biological systems and allowed capturing of their most statistically representative spectral features. Remarkably, this tool proved to be successful in extracting meaningful biological information from the datasets by yielding principal components distinguishing the cornified layers from the metabolically active epidermal cells. Finally, on the basis of multiple ToF-SIMS acquisitions, we showed that this methodology allows for the convenient production of experimental replicates, a key feature often difficult to achieve in ex vivo approaches.
The identification of sea turtle behaviours is a prerequisite to predicting the activities and time-budget of these animals in their natural habitat over the long term. However, this is hampered by a ...lack of reliable methods that enable the detection and monitoring of certain key behaviours such as feeding. This study proposes a combined approach that automatically identifies the different behaviours of free-ranging sea turtles through the use of animal-borne multi-sensor recorders (accelerometer, gyroscope and time-depth recorder), validated by animal-borne video-recorder data. We show here that the combination of supervised learning algorithms and multi-signal analysis tools can provide accurate inferences of the behaviours expressed, including feeding and scratching behaviours that are of crucial ecological interest for sea turtles. Our procedure uses multi-sensor miniaturized loggers that can be deployed on free-ranging animals with minimal disturbance. It provides an easily adaptable and replicable approach for the long-term automatic identification of the different activities and determination of time-budgets in sea turtles. This approach should also be applicable to a broad range of other species and could significantly contribute to the conservation of endangered species by providing detailed knowledge of key animal activities such as feeding, travelling and resting.
COVID-19 vaccination raised concerns about its potential effects on physical performance. To assess the impact of COVID-19 vaccination on the perceived change in physical performance, we conducted an ...online survey among elite athletes from Belgium, Canada, France and Luxembourg, with questions about socio-demographics, COVID-19 vaccination, perceived impact on physical performance and perceived pressure to get vaccinated. Full vaccination was defined as two doses of mRNA or vector vaccine or a heterologous vaccine scheme. Among 1106 eligible athletes contacted, 306 athletes answered the survey and were included in this study. Of these, 72% perceived no change in their physical performance, 4% an improvement and 24% a negative impact following full COVID-19 vaccination. For 82% of the included athletes, the duration of the negative vaccine reactions was ≤3 days. After adjustment for potential confounding variables, practicing an individual sport, a duration of vaccine reactions longer than 3 days, a high level of vaccine reaction and the perceived pressure to get vaccinated were independently associated with a perceived negative impact on physical performance of more than 3 days after the vaccination. The perceived pressure to get vaccinated appears to be a parameter associated with the negative perceived change in the physical performance and deserves further consideration.
Research is ongoing to develop multipurpose vaginal rings to be used continuously for contraception and to prevent Human Immunodeficiency Virus (HIV) infection. Contraceptive vaginal rings (CVRs) are ...available in a number of countries and are most of the time used intermittently i.e. three weeks out of a 4-week cycle. Efficacy trials with a dapivirine-containing vaginal ring for HIV prevention are ongoing and plans to develop multi-purpose vaginal rings for prevention of both HIV and pregnancy have been elaborated. In contrast with the CVRs, multi-purpose vaginal rings will have to be used continuously. Women who continuously use a CVR will no longer have menses. Furthermore, some safety aspects of CVR use have never been studied in-depth in the past, such as the impact of the vaginal ring on the vaginal microbiota, biofilm formation and induction of inflammation. We studied acceptability and these novel aspects of safety in Rwandan women. Although significant progress has been made over the past decade, Rwanda still has a high unmet need for contraception (with 47% unplanned births) and a generalized HIV epidemic, and CVRs are not yet available.
We will conduct an open label, single centre, randomized controlled trial. A total of 120 HIV-negative women will be randomized to intermittent CVR use (to allow menstruation) or continuous CVR use. Women will be followed for a maximum of 14 weeks. In parallel, we will conduct a qualitative study using in-depth interview and focus group discussion methodology.
In addition to evaluating the safety and acceptability of intermittent and continuous CVR use in Rwandan women, we hope that our findings will inform the development of future multipurpose vaginal rings, will prepare Rwandan study populations for future clinical trials of multipurpose vaginal rings, and will pave the way for introduction of CVRs on African markets.
Clinicaltrials.gov NCT01796613 . Registered 14 February 2013.
•High variability was found between national UTI treatment guidelines in Europe.•The observed differences may in part be due to unavailability of antibiotics.•A more systematic approach to resistance ...surveillance should be promoted.
Appropriate antibiotic use for urinary tract infections (UTIs) is important in order to provide effective and safe treatment while minimising the risk of antimicrobial resistance development. This survey was carried out to compare existing national guidelines for UTIs in Europe. Experts in 37 European countries were asked to participate. An electronic questionnaire was used to obtain information on treatment recommendations, factors considered important when setting guidelines, acceptable resistance rates for empirical therapy, evidence grading, and existing resistance surveillance for uropathogens. Treatment guidelines and antimicrobial susceptibility data were collected. In total, 22 experts (59%) responded to the survey. National guidelines were missing in four countries and data were incomplete in three cases. Fifteen national guidelines published between 2004 and 2017 were included in the analysis. Great variability was found between guidelines in the selection of antibiotics, dosing regimens and treatment duration. For example, 10 different antibiotics were recommended as first-line therapy for uncomplicated cystitis. National surveillance data on antimicrobial susceptibility of uropathogens were available in 13 of 15 countries. Resistance epidemiology could not explain the observed differences between guidelines, and comparison of resistance rates was hampered by variations in methods. This study revealed major differences in treatment guidelines for UTIs within Europe, indicating that there are opportunities for improvement. More clinical research and a more systematic and stratified approach to resistance surveillance, including also antibiotics that are currently not available in all countries, is needed.
External stimuli are powerful tools that naturally control protein assemblies and functions. For example, during viral entry and exit changes in pH are known to trigger large protein conformational ...changes. However, the molecular features stabilizing the higher pH structures remain unclear. Here we elucidate the conformational change of a self-assembling peptide that forms either small or large nanotubes dependent on the pH. The sub-angstrom high-pH peptide structure reveals a globular conformation stabilized through a strong histidine-serine H-bond and a tight histidine-aromatic packing. Lowering the pH induces histidine protonation, disrupts these interactions and triggers a large change to an extended β-sheet-based conformation. Re-visiting available structures of proteins with pH-dependent conformations reveals both histidine-containing aromatic pockets and histidine-serine proximity as key motifs in higher pH structures. The mechanism discovered in this study may thus be generally used by pH-dependent proteins and opens new prospects in the field of nanomaterials.
Self-assembled nanoarchitectures based on biological molecules are attractive because of the simplicity and versatility of the building blocks. However, size control is still a challenge. This ...control is only possible when a given system is deeply understood. Such is the case with the lanreotide acetate, an octapeptide salt that spontaneously forms monodisperse nanotubes when dissolved into pure water. Following a structural approach, we have in the past demonstrated the possibility to tune the diameter of these nanotubes while keeping a strict monodispersity, either by chemical modification of one precise amino acid on the peptide sequence or by changing the size of the counterions. On the basis of these previous studies, we replaced monovalent counterions by divalent ones to vary the number of walls. Indeed, in the present work, we show that lanreotide associated with a divalent counterion forms double-walled nanotubes while keeping the average diameter constant. However, the strict monodispersity of the number of walls was unexpected. We propose that the divalent counterions create an adhesion force that can drive the wall packing. This adhesion force is counterbalanced by a mechanical one that is related to the stiffness of the peptide wall. By taking into account these two opposite forces, we have built a general model that fully explains why the lanreotide nanotubes formed with divalent counterions possess two walls and not more.
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