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Abstract Background Vaginal microbiota composition is associated with spontaneous preterm birth (sPTB), depending on ethnicity. Host-microbiota interactions are thought to play an important underlying role in this association between ethnicity, vaginal microbiota and sPTB. Methods In a prospective cohort of nulliparous pregnant women, we assessed vaginal microbiota composition, vaginal immunoglobulins (Igs), and local inflammatory markers. We performed a nested case–control study with 19 sPTB cases, matched based on ethnicity and midwifery practice to 19 term controls. Results Of the 294 included participants, 23 pregnancies ended in sPTB. We demonstrated that Lactobacillus iners-dominated microbiota, diverse microbiota, and ethnicity were all independently associated with sPTB. Microbial Ig coating was associated with both microbiota composition and ethnicity, but a direct association with sPTB was lacking. Microbial IgA and IgG coating were lowest in diverse microbiota, especially in women of any ethnic minority. When correcting for microbiota composition, increased microbial Ig coating correlated with increased inflammation. Conclusion In these nulliparous pregnant women, vaginal microbiota composition is strongly associated with sPTB. Our results support that vaginal mucosal Igs might play a pivotal role in microbiota composition, microbiota-related inflammation, and vaginal community disparity within and between ethnicities. This study provides insight in host-microbe interaction, suggesting that vaginal mucosal Igs play an immunomodulatory role similar to that in the intestinal tract. Video Abstract

Abstract Background Procedural sedation and analgesia (PSA) is a technique of administering sedatives to induce a state that allows the patient to tolerate painful procedures while maintaining cardiorespiratory function, a condition that is frequently desired prehospital. Non-physician prehospital clinicians often have a limited scope of practice when it comes to providing analgesia and sedation; sometimes resulting in a crew request for back-up from physician-staffed prehospital services.“. This is also the case if sedation is desirable. Advanced practice providers (APPs), who are legally authorized and trained to carry out this procedure, may be a solution when the physician-staffed service is not available or will not be available in time. Methods The aim of this study is to gain insight in the circumstances in which an APP, working at the Dutch ambulance service “RAV Brabant MWN” from January 2019 to December 2022, uses propofol for PSA or to provide sedation. With this a retrospective observational document study we describe the characteristics of patients and ambulance runs and evaluates the interventions in terms of safety. Results During the study period, the APPs administered propofol 157 times for 135 PSA and in 22 cases for providing sedation. The most common indication was musculoskeletal trauma such as fracture care or the reduction of joint dislocation. In 91% of the situations where propofol was used, the predetermined goal e.g. alignment of fractured extremity, repositioning of luxated joint or providing sedation the goal was achieved. There were 12 cases in which one or more adverse events were documented and all were successfully resolved by the APP. There were no cases of laryngospam, airway obstruction, nor anaphylaxis. None of the adverse events led to unexpected hospitalization or death. Conclusion During the study period, the APPs performed 135 PSAs and provided 22 sedations. The success rate of predetermined goals was higher than that stated in the literature. Although there were a number of side effects, their incidences were lower than those reported in the literature, and these were resolved by the APP during the episode of care. Applying a PSA by an APP at the EMS “RAV Brabant MWN” appears to be safe with a high success rate.

Per- and polyfluoroalkyl substances (PFAS) receive global attention due to their adverse effects on human health and the environment. Fish consumption is a major source of human PFAS exposure. The aim of this work was to address the lack of harmonization within legislations (in the EU and the USA) and highlight the level of PFAS in fish exposed to pollution from diffuse sources in the context of current safety thresholds. A non-exhaustive literature review was carried out to obtain PFAS concentrations in wild fish from the Norwegian mainland, Svalbard, the Netherlands, the USA, as well as sea regions (North Sea, English Channel, Atlantic Ocean), and farmed fish on the Dutch market. Median sum wet weight concentrations of PFOA, PFNA, PFHxS, and PFOS ranged between 0.1 µg kg−1 (farmed fish) and 22 µg kg−1 (Netherlands eel). Most concentrations fell below the EU environmental quality standard (EQSbiota) for PFOS (9.1 µg kg−1) and would not be defined as polluted in the EU. However, using recent tolerable intake or reference dose values in the EU and the USA revealed that even limited fish consumption would lead to exceedance of these thresholds – possibly posing a challenge for risk communication.

Abstract A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Background and purpose: For locally advanced non-small cell lung cancer (LA-NSCLC), intensity-modulated proton therapy (IMPT) can reduce organ at risk (OAR) doses compared to intensity-modulated radiotherapy (IMRT). Deep inspiration breath hold (DIBH) reduces OAR doses compared to free breathing (FB) in IMRT. In IMPT, differences in dose distributions and robustness between DIBH and FB are unclear. In this study, we compare DIBH to FB in IMPT, and IMPT to IMRT. Materials and methods: Fortyone LA-NSCLC patients were prospectively included. 4D computed tomography images (4DCTs) and DIBH CTs were acquired for treatment planning and during weeks 1 and 3 of treatment. A new system for automated robust planning was developed and used to generate a FB and a DIBH IMPT plan for each patient. Plans were compared in terms of dose-volume parameters and normal tissue complication probabilities (NTCPs). Dose recalculations on repeat CTs were used to compare inter-fraction plan robustness. Results: In IMPT, DIBH reduced median lungs Dmean from 9.3 Gy(RBE) to 8.0 Gy(RBE) compared to FB, and radiation pneumonitis NTCP from 10.9 % to 9.4 % (p

Metal additive manufacturing is a promising technology for the production of functional medical products, due to its high shape complexity and resolution, and ability to withstand sterilization temperatures. This study explores the possibility of designing a completely non-assembly steerable surgical instrument using Selective Laser Melting. Despite its advantages for medical devices, the rough surface quality of unfinished parts can be problematic for non-assembly designs, leading to increased friction and wear in rigid body mechanisms and tendon-actuated mechanisms. We investigated printing of rolling contact joints with crossed flexures as low-friction joints, adjusted for printing in titanium for the design of the instrument. Grid-based lattice structures were incorporated as miniature flexures, and we explored the influence of various grid sizes on the flexibility and bending stiffness of the lattices. Based on this exploration, we altered the rolling joint configuration from two crossed flexures to a single straight flexure for our design. The resulting steerable surgical instrument design is completely non-assembly, including its actuation, facilitates easy removal of support structures, and requires no surface finishing steps. It has a diameter of less than 20 mm, facilitates opening and closing of a grasper, and steering of the grasper by 20 degrees.

BackgroundMR-Linac allows for daily online treatment adaptation to the observed geometry of tumor targets and organs at risk (OARs). Manual delineation for head and neck cancer (HNC) patients takes 45-75 minutes, making it unsuitable for online adaptive radiotherapy. This study aims to clinically and dosimetrically validate an in-house developed algorithm which automatically delineates the elective target volume and OARs for HNC patients in under a minute.MethodsAuto-contours were generated by an in-house model with 2D U-Net architecture trained and tested on 52 MRI scans via leave-one-out cross-validation. A randomized selection of 684 automated and manual contours (split half-and-half) was presented to an oncologist to perform a blind test and determine the clinical acceptability. The dosimetric impact was investigated for 13 patients evaluating the differences in dosage for all structures.ResultsAutomated contours were generated in 8 seconds per MRI scan. The blind test concluded that 114 (33%) of auto-contours required adjustments with 85 only minor and 15 (4.4%) of manual contours required adjustments with 12 only minor. Dosimetric analysis showed negligible dosimetric differences between clinically acceptable structures and structures requiring minor changes. The Dice Similarity coefficients for the auto-contours ranged from 0.66 ± 0.11 to 0.88 ± 0.06 across all structures.ConclusionMajority of auto-contours were clinically acceptable and could be used without any adjustments. Majority of structures requiring minor adjustments did not lead to significant dosimetric differences, hence manual adjustments were needed only for structures requiring major changes, which takes no longer than 10 minutes per patient.

The success rate of spinal fusion surgery is mainly determined by the fixation strength of the spinal bone anchors. This study explores the use of an L-shaped spinal bone anchor that is intended to establish a macro-shape lock with the posterior cortical layer of the vertebral body, thereby increasing the pull-out resistance of the anchor. The performance of this L-shaped anchor was evaluated in lumbar vertebra phantoms (L1-L5) across four distinct perpendicular orientations (lateral, medial, superior, and inferior). During the pull-out experiments, the pull-out force, and the displacement of the anchor with respect to the vertebra was measured which allowed the determination of the maximal pull-out force (mean: 123 N ± 25 N) and the initial pull-out force, the initial force required to start motion of the anchor (mean: 23 N ± 16 N). Notably, the maximum pull-out force was observed when the anchor engaged the cortical bone layer. The results demonstrate the potential benefits of utilising a spinal bone anchor featuring a macro-shape lock with the cortical bone layer to increase the pull-out force. Combining the macro shape-lock fixation method with the conventional pedicle screw shows the potential to significantly enhance the fixation strength of spinal bone anchors.

Abstract Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.

Species with extensive geographical ranges pose special challenges to assessing drivers of wildlife disease, necessitating collaborative and large-scale analyses. The imperilled foothill yellow-legged frog (Rana boylii) inhabits a wide geographical range and variable conditions in rivers of California and Oregon (USA), and is considered threatened by the pathogen Batrachochytrium dendrobatidis (Bd). To assess drivers of Bd infections over time and space, we compiled over 2000 datapoints from R. boylii museum specimens (collected 1897–2005) and field samples (2005–2021) spanning 9° of latitude. We observed a south-to-north spread of Bd detections beginning in the 1940s and increase in prevalence from the 1940s to 1970s, coinciding with extirpation from southern latitudes. We detected eight high-prevalence geographical clusters through time that span the species' geographical range. Field-sampled male R. boylii exhibited the highest prevalence, and juveniles sampled in autumn exhibited the highest loads. Bd infection risk was highest in lower elevation rain-dominated watersheds, and with cool temperatures and low stream-flow conditions at the end of the dry season. Through a holistic assessment of relationships between infection risk, geographical context and time, we identify the locations and time periods where Bd mitigation and monitoring will be critical for conservation of this imperilled species.

Abstract The decline in amphibian populations is one of the starkest examples of the biodiversity crisis. For stream breeding amphibians, alterations to natural flow regimes by dams, water diversions, and climate change have been implicated in declines and extirpations. Identifying drivers of amphibian declines requires long time series of abundance data because amphibian populations can exhibit high natural variability. Multiple population viability analysis (MPVA) models integrate abundance data and share information from different populations to estimate how environmental factors influence population growth. Flow alteration has been linked to declines and extirpations in the Foothill Yellow‐legged Frog (Rana boylii), a stream breeding amphibian native to California and Oregon. To date, no study has jointly analyzed abundance data from populations throughout the range of R. boylii in an MPVA model. We compiled time series of egg mass counts (an index of adult female abundance) from R. boylii populations in 36 focal streams and fit an MPVA model to quantify how streamflow metrics, stream temperature, and surrounding land cover affect population growth. We found population growth was positively related to stream temperature and was higher in the years following a wet year with high total annual streamflow. Density dependence was weakest (i.e., carrying capacity was highest) for streams with high seasonality of streamflow and intermediate rates of change in streamflow during spring. Our results highlight how altered streamflow can further increase the risk of decline for R. boylii populations. Managing stream conditions to better match natural flow and thermal regimes would benefit the conservation of R. boylii populations.

Immersive Virtual Reality (IVR) has gained popularity in neurorehabilitation for its potential to increase patients’ motivation and engagement. A crucial yet relatively unexplored aspect of IVR interfaces is the patients’ representation in the virtual world, such as with an avatar. A higher level of embodiment over avatars has been shown to enhance motor performance during upper limb training and has the potential to be employed to enhance neurorehabilitation. However, the relationship between avatar embodiment and gait performance remains unexplored. In this work, we present the results of a pilot study with 12 healthy young participants that evaluates the effect of different virtual lower limb representations on foot placement accuracy while stepping over a trail of 16 virtual targets. We compared three levels of virtual representation: i) a full-body avatar, ii) only feet, and iii) no representation. Full-body tracking is computed using standard VR trackers to synchronize the avatar with the participants’ motions. Foot placement accuracy is measured as the distance between the foot’s center of mass and the center of the selected virtual target. Additionally, we evaluated the level of embodiment over each virtual representation through a questionnaire. Our findings indicate that foot placement accuracy increases with some form of virtual representation, either full-body or foot, compared to having no virtual representation. However, the foot and full-body representations do not show significant differences in accuracy. Importantly, we found a negative correlation between the level of embodiment of the foot representation and the distance between the placed foot and the target. However, no such correlation was found for the full-body representation. Our results highlight the importance of embodying a virtual representation of the foot when performing a task that requires accurate foot placement. However, showing a full-body avatar does not appear to further enhance accuracy. Moreover, our results suggest that the level of embodiment of the virtual feet might modulate motor performance in this stepping task. This work motivates future research on the effect of embodiment over virtual representations on motor control to be exploited for IVR gait rehabilitation.

Background and purposeTo quantify the increase in bladder and rectum dose of a bone marrow sparing (BMS) VMAT strategy for primary treatment of locally advanced cervical cancer (LACC).Materials and methodsTwenty patients with stage IB-IVA cervical cancer were selected for this study. The whole Pelvic Bones (PB) was taken as substitute for bone marrow. For every patient, Pareto-optimal plans were generated to explore the trade-off between rectum, bladder, and PB mean dose. The PB mean dose was decreased in steps of 1 Gy. For each step, the increase in rectum and bladder mean dose was quantified. The increase in mean dose of other OAR compared to no BMS was constrained to 1 Gy.ResultsIn total, 931 plans of 19 evaluable patients were analyzed. The average [range] mean dose of PB without BMS was 22.8 [20.7-26.2] Gy. When maximum BMS was applied, the average reduction in mean PB dose was 5.4 [3.0-6.8] Gy resulting in an average mean PB dose of 17.5 [15.8-19.8] Gy. For 2 Gy, >3 Gy, >4 Gy, and >5 Gy for 19/19, 13/19, 5/19, and 1/19 patients, respectively.ConclusionBased on the comprehensive three-dimensional Pareto front analysis, we conclude that 2-5 Gy BMS can be implemented without a clinically relevant increase in mean dose to other OAR. If BMS is too dominant, it results in a large increase in mean dose to other OAR. Therefore, we recommend implementing moderate BMS for the treatment of LACC patients with VMAT.

The fixation strength of pedicle screws could be increased by fixating along the much stronger cortical bone layer, which is not possible with the current rigid and straight bone drills. Inspired by the tsetse fly, a single-plane steerable bone drill was developed. The drill has a flexible transmission using two stacked leaf springs such that the drill is flexible in one plane and can drill along the cortical bone layer utilizing wall guidance. A proof-of-principle experiment was performed which showed that the Tsetse Drill was able to successfully drill through 5, 10 and 15 PCF cancellous bone phantom which has similar mechanical properties to severe osteoporotic, osteoporotic and healthy cancellous bone. Furthermore, the Tsetse Drill was able to successfully steer and drill along the cortical wall utilizing wall guidance for an insertion angle of 5°, 10° and 15°. The experiments conclude that the tsetse fly-inspired drilling method is successful and even allows the drilling along the cortical bone layer. The Tsetse Drill can create curved tunnels utilizing wall guidance which could increase the fixation strength of bone anchors and limit the risk of cortical breach and damage to surrounding anatomy.

Presently, many studies assess allergenicity via IgE immunoblotting and IgE binding tests; however, IgE detection does not always signal the manifestation of a clinical allergy. However, the capacity of food allergens to trigger basophils makes it possible to use the in vitro functional basophil activation test (BAT) to assess allergenicity. The effect of the Maillard reaction (MR) on the allergenic potential of processed soy proteins was evaluated by two IgE binding tests (Competitive ELISA and Inhibition ImmunoCAP), a Western Blot and a functional BAT; with the aim to analyze whether the sIgE binding results correspond to the functional assay results. The results between the IgE binding tests and the functional assay were in-line for 2 of the 6 studied patients. For one patient there was no correlation between any of the results. For the raw soy protein extract heated with glucose for 10 and 30 min (SH SPE + Glu and LH SPE + Glu, respectively), the results were in-line for only 3 out of the 6 patients. Thus, the present study shows a discrepancy between IgE binding tests and basophil stimulation when assessing the effect of soy processing on its allergenicity. Since IgE-binding capacity does not always correlate to IgE cross-linking capacity, the conclusions of the allergenic potential based on the IgE binding tests alone should be drawn with care and further studies on this matter would benefit from the inclusion of a functional assay such as the BAT.

Background: Intensity Modulated Proton Therapy (IMPT) in head and neck cancer (HNC) is susceptible to anatomical changes and patient set-up inaccuracies during the radiotherapy course, which can cause discrepancies between planned and delivered dose. The discrepancies can be counteracted by adaptive replanning strategies. This article reviews the observed dosimetric impact of adaptive proton therapy (APT) and the timing to perform a plan adaptation in IMPT in HNC. Methods: A literature search of articles published in PubMed/MEDLINE, EMBASE and Web of Science from January 2010 to March 2022 was performed. Among a total of 59 records assessed for possible eligibility, ten articles were included in this review. Results: Included studies reported on target coverage deterioration in IMPT plans during the RT course, which was recovered with the application of an APT approach. All APT plans showed an average improved target coverage for the high- and low-dose targets as compared to the accumulated dose on the planned plans. Dose improvements up to 2.5 Gy (3.5 %) and up to 4.0 Gy (7.1 %) in the D98 of the high- and low dose targets were observed with APT. Doses to the organs at risk (OARs) remained equal or decreased slightly after APT was applied. In the included studies, APT was largely performed once, which resulted in the largest target coverage improvement, but eventual additional APT improved the target coverage further. There is no data showing what is the most appropriate timing for APT. Conclusion: APT during IMPT for HNC patients improves target coverage. The largest improvement in target coverage was found with a single adaptive intervention, and an eventual second or more frequent APT application improved the target coverage further. Doses to the OARs remained equal or decreased slightly after applying APT. The most optimal timing for APT is yet to be determined.

Abstract Background Immunoglobulin A (IgA) plays an important role in maintaining a healthy intestinal microbiome, but little is known about the interaction between local immunoglobulins and the vaginal microbiome. We assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age. Results In both Lactobacillus crispatus-dominated and non-L. crispatus-dominated microbiota, IgA and IgG (unbound and bound to bacteria) were higher during menses (T = 1) compared to day 7‑11 (T = 2) and day 17‑25 (T = 3) after menses onset. The majority of vaginal bacteria are coated with IgA and/or IgG. Women with L. crispatus-dominated microbiota have increased IgA coating of vaginal bacteria compared to women with other microbiota compositions, but contained less IgA per bacterium. Presence of a dominantly IgA-coated population at T = 2 and/or T = 3 was also strongly associated with L. crispatus-dominated microbiota. In women with non-L. crispatus-dominated microbiota, more bacteria were uncoated. Unbound IgA, unbound IgG, and bound IgG levels were not associated with microbiota composition. Conclusions In conclusion, L. crispatus-dominated vaginal microbiota have higher levels of bacterial IgA coating compared to non-L. crispatus-dominated vaginal microbiota. Similar to its regulating function in the intestinal tract, we hypothesize that IgA is involved in maintaining L. crispatus-dominated microbiota in the female genital tract. This may play a role in L. crispatus-associated health benefits. Video abstract

With the increase in Natural Orifice Transluminal Endoscopic Surgery procedures, there is an increasing demand for surgical instruments with additional degrees of freedom, able to travel along tortuous pathways and guarantee dexterity and high accuracy without compromising the surrounding environment. The implementation of follow-the-leader motion in surgical instruments allows propagating the decided shape through its body and moving through curved paths avoiding sensitive areas. Due to the limited operational area and therefore the instrument size, the steerable shaft of these instruments is usually driven by cables that are externally actuated. However, a large number of degrees of freedom requires a great number of actuators, increasing the system complexity. Therefore, our goal was to design a new memory system able to impose a follow-the-leader motion to the steerable shaft of a medical instrument without using actuators. We present a memory mechanism to control and guide the cable displacements of a cable-driven shaft able to move along a multi-curved path. The memory mechanism is based on a programmable physical track with a mechanical interlocking system. The memory system, called MemoBox, was manufactured as a proof-of-concept demonstration model, measuring 70 mm × 64 mm × 6 mm with 11 programmable elements and featuring a minimum resolution of 1 mm. The prototype shows the ability to generate and shift complex 2D pathways in real-time controlled by the user.

BackgroundState-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT).MethodsFor 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored.ResultsDIBH reduced the median Dmean to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors.ConclusionCompared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.

Baked goods manufacturing parameters and fermentation conditions interfere with the nutrients content and affect their gastrointestinal fate. Pinsa Romana is a type of pizza that, recently, has been commercially rediscovered and that needed elucidation from a nutritional and digestibility perspective. In this study, six types of Pinsa Romana (five made with indirect method and one produced with straight dough technology) were characterized for their biochemical and nutritional features. Several variables like indirect (biga) Pinsa Romana production process, fermentation time and use of sourdough were investigated. The Pinsa Romana made with biga including sourdough and fermented for 48 h at 16 °C ((PR_48(SD)) resulted in the lowest predicted glycemic index, in the highest content of total peptides, total and individual free amino acids and gamma-amino butyric acid (GABA), and in the best protein quality indexes (protein efficiency ratio and nutritional index). The static in vitro digestion showed that the digesta from PR_48(SD) confirmed a reduced in vitro glycemic response after intake, and it showed a lower bioavailability of hydrophilic peptides. Furthermore, the inclusion of sourdough in biga enhanced the bioavailability of protein-related end-products including human health promoting compounds such as essential amino acids.

Abstract Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I–III CRC survivors (n = 459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment. Trial registration: NTR7099.

Per-and poly fluoroalkyl substances (PFAS) from aqueous film forming foam (AFFF) used at firefighting training facilities (FTF) contaminate waterbodies and pose a threat to human health and the environment worldwide . In this study, leaching of PFAS from historically AFFF contaminated field soil has been investigated under saturated conditions using up-flow columns for four soil samples with varying PFAS concentrations to quantify the long-term release potential of the source zone. PFOS was the most abundant PFAS present in the soils (84–98% of ΣPFAS12), varying from 358 to 1097 µg/kg and the total organic carbon (TOC) content varied from 0.73 to 2.0%. The experiment was run until a liquid to solid (L/S) ratio of 10 was reached (equivalent to 80 pore volumes or approximately 100 years of natural infiltration at the sampled field site). Results show a general trend of decreasing concentrations of short chain PFAS with increasing leaching volume. However, PFOS concentrations initially increased by 45–87% in three samples with relatively low TOC (0.7, 1.0 and 1.4%), before being reduced. In the 2.0% TOC soil PFOS concentrations continued to increase throughout the experiment. The residual PFOS content in the four soil samples showed no correlation with TOC content in the soil. Up to 50% of the initial PFOS content was retained in the soil with the lowest TOC content (0.7%), whereas all PFOS was removed in the soil with a TOC content of 1.4%. It is hypothesized that DOC present in the eluates originates from other non-fluorinated components present in AFFF that can facilitate PFAS leaching.

Abstract Background One of the most important steps before implementing short stay total hip arthroplasty (THA) is establishing patient criteria. Most existing criteria are mainly based on medical condition, but as physical functioning is associated with outcome after THA, we aim to evaluate the added value of a measure of physical functioning to predict short-stay THA. Methods We used retrospective data of 1559 patients who underwent an anterior THA procedure. Logistic regression analyses were performed to study the predictive value of preoperative variables among which preoperative physical functioning by use of the Timed Up and Go test (TUG) for short stay THA (

A vitrectome is a commonly used instrument in eye surgery, which is used to cut and aspirate the vitreous body out of the eye. The mechanism of the vitrectome consists of miniature components that need to be assembled by hand due to their size. Non-assembly 3D printing, in which fully functional mechanisms can be produced in a single production step, can help create a more streamlined production process. We propose a vitrectome design based on a dual-diaphragm mechanism, which can be produced with minimal assembly steps using PolyJet printing. Two different diaphragm designs were tested to fulfill the requirements of the mechanism: a homogenous design based on ‘digital’ materials and a design using an ortho-planar spring. Both designs were able to fulfill the required displacement for the mechanism of 0.8 mm, as well as cutting forces of at least 8 N. The requirements for the cutting speed of the mechanism of 8000 RPM were not fulfilled by both designs, since the viscoelastic nature of the PolyJet materials resulted in a slow response time. The proposed mechanism does show promise to be used in vitrectomy; however, we suggest that more research into different design directions is required.

Stereolithography is emerging as a promising additive manufacturing technology for a range of applications in the medical domain. However, for miniature, medical devices such as those used in ophthalmic surgery, a number of production challenges arise due to the small size of the components. In this work, we investigate the challenges of creating sub-millimeter features for a miniature, functional trocar using Stereolithography. The trocar cannula system is used in eye surgery to facilitate a passage for other instruments. A standard trocar consists of a hollow cannula and a flexible check valve. The research was performed in two stages: in the first stage we investigated the effect of different materials and print settings on the current design of the cannula and the valve separately, and in the second stage we used these findings to optimize the design and production process. After the first investigation, it became apparent that even though the dimensions of the trocar are within the feature size range of Stereolithography, all hollow features tended to fuse shut during printing. This effect appeared regardless of the materials or print settings, and can be attributed to refraction of the laser source. In order to circumvent this, we identified two potential strategies: (1) increasing the negative space surrounding features; and (2) decreasing the surface area per layer. By applying these strategies, we tested a new design for the cannula and valve and managed to 3D print a functional trocar, which was tested in an artificial eye. The design of the 3D printed trocar allows for further personalization depending on the specific requirements of both patient and surgeon. The proposed strategies can be applied to different applications to create miniature features using Stereolithography.