Purpose
To assess the impact of maintenance therapy and the additional impact of dexamethasone treatment on cancer-related fatigue and sleep-wake rhythms in pediatric acute lymphoblastic leukemia ...(ALL) patients and to determine the association between these outcomes.
Methods
A national cohort of pediatric ALL patients (≥ 2 years) was included (± 1 year post-diagnosis). Patients receiving dexamethasone were assessed twice (assessment with and without dexamethasone). Actigraphy assessments were used to calculate sleep-wake outcomes with nonparametric methods. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Sleep-wake rhythms and cancer-related fatigue were compared between patients participating in the assessment without dexamethasone and healthy children (linear regression) and between assessments with and without dexamethasone (mixed models). Using linear regression, associations between sleep-wake outcomes and cancer-related fatigue were determined during assessments with and without dexamethasone.
Results
Responses were collected for 125 patients (113 assessments with and 81 without dexamethasone). The sleep-wake rhythm was less stable (
p
= 0.03) and less robust (
p
= 0.01), with lower physical activity levels (
p
< 0.001) and higher cancer-related fatigue levels (
p
< 0.001) in ALL patients compared to healthy children. Physical activity was lower (
p
= 0.001) and cancer-related fatigue more severe (
p
≤ 0.001) during assessments with dexamethasone compared to without dexamethasone. Sleep-wake outcomes were significantly associated with cancer-related fatigue during periods without dexamethasone, but not during periods with dexamethasone.
Conclusion
Sleep-wake rhythms are disturbed, physical activity levels lower, and cancer-related fatigue levels higher during maintenance therapy. Interventions aimed to enhance sleep-wake rhythms during maintenance therapy could improve cancer-related fatigue. Families should be supported in coping with the additional burden of dexamethasone treatment to improve well-being of ALL patients.
How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and ...archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.
Collagen glue has been used for nearly two centuries to consolidate bone material, although its prevalence in museum collections is only now becoming visible. Identifying and removing collagen glue ...is crucial before the execution of any geochemical or molecular analyses. Palaeolithic bone objects from old excavations intended for radiocarbon dating were first analysed using ZooMS (Zooarchaeology by Mass Spectrometry) to identify the animal species, however peaks characteristic of both cattle and whale were discovered. Two extraction methods for ZooMS were tested to identify the authentic animal species of these objects, which revealed that these were originally whale bone objects that had been consolidated with cattle collagen glue. This is the first time animal collagen glue has been identified in archaeological remains with ZooMS, illustrating again the incredible versatility of this technique. Another technique, Fourier Transform Infrared Spectroscopy in Attenuated Total Reflectance mode (FTIR-ATR), was also tested if it could rapidly identify the presence of collagen glue in archaeological bone material, which was not the case. Two other cleaning methods were tested to remove bone glue contamination prior to radiocarbon dating, along with two modified collagen extraction methods for ZooMS. These methods were applied to bone blank samples (FmC = 0.0031 ± 0.0002, (n = 219), 47 336 ± 277 yr BP) that were experimentally consolidated with collagen glue and to the Palaeolithic bone material (ca. 15 000 and 12 000 yr BP). The experimental bone blanks produced excellent
C ages, suggesting the cleaning methods were successful, however the
C ages for some of the Palaeolithic material remained too young considering their contextual age, suggesting that the collagen glue contamination had most likely cross-linked to the authentic collagen molecule. More research is needed in order to gain a deeper understanding of the occurrence and elimination of cross-linked collagen-based glues in material from museum collections.
Purpose
The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral ...neuropathy (VIPN) in Dutch pediatric oncology patients aged 5–18 years.
Methods
Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0–32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0–18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants.
Results
Among the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (
r
= 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both
p
< .001). Reliability as measured within the intra-rater group (
n
= 10) (intra-class correlation coefficient (ICC
agreement
) = 0.64, standard error of measurement (SEM
agreement
) = 2.92, and smallest detectable change (SDC
agreement
) = 8.1) and within the inter-rater subgroup (
n
= 10) (ICC
agreement
= 0.63, SEM
agreement
= 3.7, and SDC
agreement
= 10.26) indicates insufficient reliability.
Conclusion
The Dutch version of the ped-mTNS appears to have good construct validity for assessing VIPN in a Dutch pediatric oncology population, whereas reliability appears to be insufficient and measurement error high. To improve standardization of VIPN assessment in children, future research aimed at evaluating and further optimizing the psychometric characteristics of the ped-mTNS is needed.
Museum collections are extremely valuable sources of material for ongoing research, although the conservation history of some objects is not always recorded, which can be problematic for chemical ...analyses. While most contamination is removed using the acid-base-acid treatment, this may not be the case for cross-linked contamination. The XAD resin protocol was implemented at the radiocarbon (14C) laboratory in the Muséum national d’Histoire naturelle, and the setup was tested using known age bone samples and a consolidated Palaeolithic bone. Known age samples were consolidated with shellac or Paraloid, aged for a month, treated with or without the XAD resin and 14C dated. Bone blank results showed that XAD resin was able to remove shellac, which was not the case for the ABA-only method. Results from VIRI I were more variable and VIRI F was possibly too young to show the effects of the consolidants. Two 14C dates on the Palaeolithic bone after XAD treatment are statistically the same, while a sample without XAD treatment was significantly older, suggesting that the contaminant was not fully removed by the ABA-only treatment. This study demonstrates the potential of the XAD treatment to clean heritage bone samples stored in museums prior to geochemical analyses.
Regenerative endodontics exploits the mineralization potential of stem cells from the apical papilla (SCAPs) in order to promote root maturation of permanent immature teeth. SCAPs may encounter ...post-disinfection residual bacteria either in planktonic or in biofilm growth mode. Bacterial components bind to Toll-like receptors (TLRs) and trigger pro-inflammatory responses. We hypothesized that biofilm-triggered TLR activation affects the mineralization potential of human SCAPs. SCAPs were challenged with conditioned media derived from standardized dual-species biofilms and planktonic bacterial cultures and their inflammatory status and mineralization capacity were studied. Bacterial products from both growth modes (planktonic vs. biofilm) compromised cell viability, proliferation and mineralization capacity of SCAPs, but in a species- and growth mode-dependent fashion. While TLR4 expression remained unaffected, TLR2 expression was upregulated coinciding with a pro-inflammatory activation of SCAPs. Moreover, TLR and its downstream TGF-β-associated kinase (TAK1) appeared to be blocking mineralization, as inhibition of these factors restored it. In conclusion, bacterial products promoted the pro-inflammatory status and inhibited mineralization of human SCAPs in a TLR-, species-, and culture-dependent fashion. TLR2 emerged as the pivotal mediator of these responses and further research is warranted towards the judicious manipulation of SCAPs in order to modify the untoward events of TLR-priming and signaling.
Background
Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15–20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been ...introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation.
Methods
This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009–2015) and cohort B (period 2015–2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts.
Results
Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (
p
= 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (
p
< 0.001). The stoma-free patient rate was 24% higher in cohort B (
p
< 0.001).
Conclusion
Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.
Taphonomic research of bones can provide additional insight into a site's formation and development, the burial environment and ongoing post-mortem processes. A total of 30 tortoise (Cylindraspis) ...femur bone samples from the Mare aux Songes site (Mauritius) were studied histologically, assessing parameters such as presence and type of microbial alteration, inclusions, staining/infiltrations, the degree of microcracking and birefringence. The absence of microbial attack in the 4200year old Mare aux Songes bones suggests the animals rapidly entered the soil whole-bodied and were sealed anoxically, although they suffered from biological and chemical degradation (i.e. pyrite formation/oxidation, mineral dissolution and staining) related to changes in the site's hydrology. Additionally, carbon and nitrogen stable isotopes were analysed to obtain information on the animals' feeding behaviour. The results show narrowly distributed δ13C ratios, indicating a terrestrial C3 plant-based diet, combined with a wide range in δ15N ratios. This is most likely related to the tortoises' drought-adaptive ability to change their metabolic processes, which can affect the δ15N ratios. Furthermore, ZooMS collagen fingerprinting analysis successfully identified two tortoise species (C. triserrata and C. inepta) in the bone assemblage, which, when combined with stable isotope data, revealed significantly different δ15N ratios between the two tortoise species. As climatic changes around this period resulted in increased aridity in the Mascarene Islands, this could explain the extremely elevated δ15N ratio in our dataset. The endemic fauna was able to endure the climatic changes 4200years ago, although human arrival in the 17th century changed the original habitat to such an extent that it resulted in the extinction of several species. Fortunately we are still able to study these extinct tortoises due to the beneficial conditions of their burial environment, resulting in excellent bone preservation.
•Use bone histological analysis to provide information on site formation processes•Assess the state of bone preservation and identify the type of degradation processes•Assess the palaeodietary behaviour of extinct giant tortoises•ZooMS collagen fingerprinting successfully separated two extinct tortoise species•ZooMS and stable isotope data combined revealed species-related dietary preferences
The aim of the study was to investigate whether an increased risk of injury occurrence can be determined through frequent anthropometric measurements in elite-standard youth soccer players. Over the ...course of one season, we followed 101 male elite-standard youth soccer players between 11 and 19 years of age. Height and body mass were monitored at monthly measurement intervals and fat percentage was assessed every 3 months by use of the sum of skinfold method. Growth in height (cm), alternations in body mass index (kg/m(2)), fat percentage and fat-free mass index (kg/m(2)) were calculated. Injuries were recorded in accordance with the recommendations of the FIFA Consensus Model for Injury Registration. Odds ratio scores and 95% confidence intervals were calculated using binary logistic regression analyses. The following anthropometric injury risk factors were identified: ≥ 0.6 centimeter growth per month (p=0.03; OR=1.63; 95% CI: 1.06-2.52), ≥ 0.3 kg/m(2) increase of body mass index value per month (p=0.03; OR=1.61; 95% CI: 1.04-2.49) and low fat percentage; i. e., < 7% for players aged 11-16 and < 5% for players over 16 years (p=0.01; OR=1.81; 95% CI: 1.18-2.76). Individual monitoring of anthropometrics provides useful information to determine increased risk of injury occurrence in elite-standard youth soccer.