The impact of pediatric obesity on biomechanical differences across the gait cycle at three walking speeds.

BACKGROUND: Obesity impacts a child's ability to walk with resulting biomechanical adaptations; however, existing research has not comprehensively compared differences across the gait cycle. We examined differences in lower extremity biomechanics across the gait cycle between children with and without obesity at three walking speeds. METHODS: Full gait cycles of age-matched children with obesity (N = 10; BMI: 25.7 ± 4.2 kg/m2) and without obesity (N = 10; BMI: 17.0 ± 1.9 kg/m2) were analyzed at slow, normal, and fast walking speeds. Main and interaction effects of group and speed across hip, knee, and ankle joint angles and moments in sagittal, frontal, and transverse planes were analyzed using one-dimensional statistical parametric mapping. FINDINGS: Compared to children without obesity, children with obesity had greater hip adduction during mid-stance, while also producing greater hip extensor moments during early stance phase, abductor moments throughout most of stance, and hip external rotator moments during late stance. Children with obesity recorded greater knee flexor, knee extensor and knee internal rotator moments during early stance, and knee external rotator moments in late stance than children without obesity; children with obesity also demonstrated greater ankle plantarflexor moments throughout mid and late stance. Interaction effects existed within joint kinetics data; children with obesity produced greater hip extensor moments at initial contact and toe-off when walking at fast compared to normal walking speed. INTERPRETATION: While few kinematic differences existed between the two groups, children with obesity exhibited greater moments at the hip, knee, and ankle during critical periods of controlling and stabilizing mass.

Workforce perspective on racial and ethnic equity in early childhood autism evaluation and treatment: "The cornerstone of everything we do".

LAY ABSTRACT: Black and non-White Latinx children tend to receive autism diagnoses later in life and with a higher degree of impairment than White children. The purpose of this study was to learn what is currently helping as well as preventing Black and non-White Latinx children from getting access to autism evaluation and services. We held virtual interviews with 26 experts who work with autistic children and their families, including clinical providers, researchers, advocates, and policymakers/government representatives. From these interviews, we identified four themes that have an impact on equity in autism services: (1) who makes up the workforce, (2) workforce capacity and accessibility, (3) workforce payment structure, and (4) changes due to the COVID-19 pandemic. These findings show the need for improved workforce diversity, autism-specific education, payment structures, and additional support for workforce members to avoid burnout. To make childhood autism services more equitable, diversity in recruitment across training levels, cultural awareness, increased autism education for all pediatric providers, and partnerships with caregivers as experts must be prioritized. These investments in the autism workforce will allow professionals in the field to better meet the needs of children and families from Black and non-White Latinx communities and achieve equity in early childhood autism services.

Toxic elements in arctic and sub-arctic brown bears: Blood concentrations of As, Cd, Hg and Pb in relation to diet, age, and human footprint.

Contamination with arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) is a global concern impairing resilience of organisms and ecosystems. Proximity to emission sources increases exposure risk but remoteness does not alleviate it. These toxic elements are transported in atmospheric and oceanic pathways and accumulate in organisms. Mercury accumulates in higher trophic levels. Brown bears (Ursus arctos), which often live in remote areas, are long-lived omnivores, feeding on salmon (Oncorhynchus spp.) and berries (Vaccinium spp.), resources also consumed by humans. We measured blood concentrations of As, Cd, Hg and Pb in bears (n = 72) four years and older in Scandinavia and three national parks in Alaska, USA (Lake Clark, Katmai and Gates of the Arctic) using high-resolution, inductively-coupled plasma sector field mass spectrometry. Age and sex of the bears, as well as the typical population level diet was associated with blood element concentrations using generalized linear regression models. Alaskan bears consuming salmon had higher Hg blood concentrations compared to Scandinavian bears feeding on berries, ants (Formica spp.) and moose (Alces). Cadmium and Pb blood concentrations were higher in Scandinavian bears than in Alaskan bears. Bears using marine food sources, in addition to salmon in Katmai, had higher As blood concentrations than bears in Scandinavia. Blood concentrations of Cd and Pb, as well as for As in female bears increased with age. Arsenic in males and Hg concentrations decreased with age. We detected elevated levels of toxic elements in bears from landscapes that are among the most pristine on the planet. Sources are unknown but anthropogenic emissions are most likely involved. All study areas face upcoming change: Increasing tourism and mining in Alaska and more intensive forestry in Scandinavia, combined with global climate change in both regions. Baseline contaminant concentrations as presented here are important knowledge in our changing world.

Correlating gut microbial membership to brown bear health metrics.

The internal mechanisms responsible for modulating physiological condition, particularly those performed by the gut microbiome (GMB), remain under-explored in wildlife. However, as latitudinal and seasonal shifts in resource availability occur, the myriad micro-ecosystem services facilitated by the GMB may be especially important to wildlife health and resilience. Here, we use brown bears (Ursus arctos) as an ecological model to quantify the relationship between wildlife body condition metrics that are commonly used to assess individual and population-level health and GMB community composition and structure. To achieve these aims, we subsampled brown bear fecal samples collected during United States National Park Service research activities at three National Parks and Preserves (Katmai, Lake Clark, and Gates of the Arctic) and extracted microbial DNA for 16S rRNA amplicon sequencing and microbial taxonomic classification. We analyzed GMB communities using alpha diversity indices, subsequently using Spearman's correlation analysis to examine relationships between alpha diversity and brown bear health metrics. We found no differences in GMB composition among bears with differing body conditions, nor any correlations between alpha diversity and body condition. Our results indicate that GMB composition reflects diverse foraging strategies while allowing brown bears to achieve similar body condition outcomes.

Intrinsic and extrinsic factors influence on an omnivore's gut microbiome.

Gut microbiomes (GMBs), complex communities of microorganisms inhabiting the gastrointestinal tracts of their hosts, perform countless micro-ecosystem services such as facilitating energy uptake and modulating immune responses. While scientists increasingly recognize the role GMBs play in host health, the role of GMBs in wildlife ecology and conservation has yet to be realized fully. Here, we use brown bears (Ursus arctos) as an ecological model to (1) characterize GMB community composition associated with location, season, and reproductive condition of a large omnivore; (2) investigate how both extrinsic and intrinsic factors influence GMB community membership and structure; and (3) quantify differences in GMB communities among different locations, seasons, sex, and reproductive conditions. To achieve these aims, we subsampled brown bear fecal samples collected during United States National Park Service research activities at three National Parks and Preserves (Katmai, Lake Clark, and Gates of the Arctic) and extracted microbial DNA for 16S rRNA amplicon sequencing and microbial taxonomic classification. We analyzed GMB communities using alpha and beta diversity indices, subsequently using linear mixed models to examine relationships between alpha diversity and extrinsic and intrinsic factors. Katmai brown bears hosted the greatest alpha diversity, whereas Gates brown bears hosted the least alpha diversity. Our results indicate that location and diet drive GMB variation, with bears hosting less phylogenetic diversity as park distance inland increases. Monitoring brown bear GMBs could enable managers to quickly detect and assess the impact of environmental perturbations on brown bear health. By integrating macro and micro-ecological perspectives we aim to inform local and landscape-level management decisions to promote long-term brown bear conservation and management.

DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with 131I.

AIM: The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [131I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy. MATERIAL AND METHODS: Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [131I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70% ethanol and stored at - 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs). RESULTS: Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h-1, which is in good agreement with data obtained from external irradiation with γ- or X-rays. CONCLUSION: This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after 131I exposure is comparable to that of external irradiation with γ- or X-rays.

Improved cancer detection in Waldeyer's tonsillar ring by 68Ga-FAPI PET/CT imaging.

PURPOSE: In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [18F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [18F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer's tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer's tonsillar ring, the novel PET tracer [68Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. METHODS: Eight patients with suspicion of a malignant tumor in Waldeyer's tonsillar ring or a CUP syndrome were examined. PET/CT scans with [18F]-FDG and [68Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. RESULTS: Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [18F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [68Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for 18F-FDG and 16.06 ± 6.29 for 68Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [18F]FDG and 3.55 ± 0.47 for [68Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [18F] FDG (p = 0.03). Mean TBRmax for the [68Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [18F]FDG (10.90 vs. 4.11). CONCLUSION: Non-invasive imaging of FAP expression by [68Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [18F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [68Ga]FAPI PET/CT imaging.

Splitting hairs: dietary niche breadth modelling using stable isotope analysis of a sequentially grown tissue.

Stable isotope data from durable, sequentially grown tissues (e.g. hair, claw, and baleen) is commonly used for modelling dietary niche breadth. The use of tissues grown over multiple months to years, however, has the potential to complicate isotopic niche breadth modelling, as time-averaged stable isotope signals from whole tissues may obscure information available from chronologically resolved stable isotope signals in serially sectioned tissues. We determined if whole samples of brown bear guard hair produced different isotopic niche breadth estimates than those produced from subsampled, serially sectioned samples of the same tissue from the same set of individuals. We sampled guard hair from brown bears (Ursus arctos) in four regions of Alaska with disparate biogeographies and dietary resource availability. Whole hair and serially sectioned hair samples were used to produce paired isotopic dietary niche breadth estimates for each region in the SIBER Bayesian model framework in R. Isotopic data from serially sectioned hair consistently produced larger estimates of isotopic dietary niche breadth than isotope data from whole hair samples. Serial sampling captures finer-scale changes in diet and when cumulatively used to estimate isotopic niche breadth, the serially sampled isotope data more fully captures dietary variability and true isotopic niche breadth.

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

BACKGROUND: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. METHODS: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. RESULTS: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults.

BACKGROUND: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. METHODS: 29 cognitively unimpaired old-aged adults (age = 70.03 ±â€¯5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression' (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. RESULTS: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. CONCLUSIONS: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD.

Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018.

All living organisms secrete molecules for intercellular communication. Recent research has revealed that extracellular vesicles (EVs) play an important role in inter-organismal cell-to-cell communication by transporting diverse messenger molecules, including RNA, DNA, lipids and proteins. These discoveries have raised fundamental questions regarding EV biology. How are EVs biosynthesized and loaded with messenger/cargo molecules? How are EVs secreted into the extracellular matrix? What are the EV uptake mechanisms of recipient cells? As EVs are produced by all kind of organisms, from unicellular bacteria and protists, filamentous fungi and oomycetes, to complex multicellular life forms such as plants and animals, basic research in diverse model systems is urgently needed to shed light on the multifaceted biology of EVs and their role in inter-organismal communications. To help catalyse progress in this emerging field, a mini-symposium was held in Munich, Germany in August 2018. This report highlights recent progress and major questions being pursued across a very diverse group of model systems, all united by the question of how EVs contribute to inter-organismal communication.

Nest use dynamics of an undisturbed population of bald eagles.

Management or conservation targets based on demographic rates should be evaluated within the context of expected population dynamics of the species of interest. Wild populations can experience stable, cyclical, or complex dynamics, therefore undisturbed populations can provide background needed to evaluate programmatic success. Many raptor species have recovered from large declines caused by environmental contaminants, making them strong candidates for ongoing efforts to understand population dynamics and ecosystem processes in response to human-caused stressors. Dynamic multistate occupancy models are a useful tool for analyzing species dynamics because they leverage the autocorrelation inherent in long-term monitoring datasets to obtain useful information about the dynamic properties of population or reproductive states. We analyzed a 23-year bald eagle monitoring dataset in a dynamic multistate occupancy modeling framework to assess long-term nest occupancy and reproduction in Lake Clark National Park and Preserve, Alaska. We also used a hierarchical generalized linear model to understand changes in nest productivity in relation to environmental factors. Nests were most likely to remain in the same nesting state between years. Most notably, successful nests were likely to remain in use (either occupied or successful) and had a very low probability of transitioning to an unoccupied state in the following year. There was no apparent trend in the proportion of nests used by eagles through time, and the probability that nests transitioned into or out of the successful state was not influenced by temperature or salmon availability. Productivity was constant over the course of the study, although warm April minimum temperatures were associated with increased chick production. Overall our results demonstrate the expected nesting dynamics of a healthy bald eagle population that is largely free of human disturbance and can be used as a baseline for the expected dynamics for recovering bald eagle populations in the contiguous 48 states.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Biokinetics, dosimetry, and radiation risk in infants after 99mTc-MAG3 scans.

BACKGROUND: Renal scans are among the most frequent exams performed on infants and toddlers. Due to the young age, this patient group can be classified as a high-risk group with a higher probability for developing stochastic radiation effects compared to adults. As there are only limited data on biokinetics and dosimetry in this patient group, the aim of this study was to reassess the dosimetry and the associated radiation risk for infants undergoing 99mTc-MAG3 renal scans based on a retrospective analysis of existing patient data. Consecutive data were collected from 20 patients younger than 20 months (14 males; 6 females) with normal renal function undergoing 99mTc-MAG3 scans. To estimate the patient-specific organ activity, a retrospective calibration was performed based on a set of two 3D-printed infant kidneys filled with known activities. Both phantoms were scanned at different positions along the anteroposterior axis inside a water phantom, providing depth- and size-dependent attenuation correction factors for planar imaging. Time-activity curves were determined by drawing kidney, bladder, and whole-body regions-of-interest for each patient, and subsequently applying the calibration factor for conversion of counts to activity. Patient-specific time-integrated activity coefficients were obtained by integrating the organ-specific time-activity curves. Absorbed and effective dose coefficients for each patient were assessed with OLINDA/EXM for the provided newborn and 1-year-old model. The risk estimation was performed individually for each of the 20 patients with the NCI Radiation Risk Assessment Tool. RESULTS: The mean age of the patients was 7.0 ± 4.5 months, with a weight between 5 and 12 kg and a body size between 60 and 89 cm. The injected activities ranged from 12 to 24 MBq of 99mTc-MAG3. The patients' organ-specific mean absorbed dose coefficients were 0.04 ± 0.03 mGy/MBq for the kidneys and 0.27 ± 0.24 mGy/MBq for the bladder. The mean effective dose coefficient was 0.02 ± 0.02 mSv/MBq. Based on the dosimetry results, an evaluation of the excess lifetime risk for the development of radiation-induced cancer showed that the group of newborns has a risk of 16.8 per 100,000 persons, which is about 12% higher in comparison with the 1-year-old group with 14.7 per 100,000 persons (all values are given as mean plus/minus one standard deviation except otherwise specified). CONCLUSION: In this study, we retrospectively derived new data on biokinetics and dosimetry for infants with normal kidney function after undergoing renal scans with 99mTc-MAG3. In addition, we analyzed the associated age- and gender-specific excess lifetime risk due to ionizing radiation. The radiation-associated stochastic risk increases with the organ doses, taking age- and gender-specific influences into account. Overall, the lifetime radiation risk associated with the 99mTc-MAG3 scans is very low in comparison to the general population risk for developing cancer.

Nasal Nitric Oxide Measurement and a Modified PICADAR Score for the Screening of Primary Ciliary Dyskinesia in Adults with Bronchiectasis.

Background Determining the underlying diagnosis is essential for the targeted and specific treatment of bronchiectasis. Primary ciliary dyskinesia (PCD) is a rare genetic disease, which is characterized by abnormalities in ciliary structure and/or function and which may result in bronchiectasis. The disease is probably underestimated among adults with bronchiectasis due to the fact that extensive diagnostic testing is required and that the recognition of PCD is low. Objective To evaluate a feasible screening algorithm for PCD among adults with bronchiectasis. Methods Data from all patients who presented to our bronchiectasis outpatient clinic from June 2010 until July 2016 were retrospectively analysed from our database. Nasal NO (nNO) and a modified PICADAR score (PrImary CiliAry DyskinesiA Rule) were measured and compared in the two groups of PCD-bronchiectasis and non-PCD-bronchiectasis. Results 185 of 365 patients (75 males, 110 females) had a sufficient measurement of nNO concentration and complete clinical data and were eligible for analysis. The mean (SD) nNO concentration in nL/ml was significant lower in the PCD group compared to the non-PCD group (25 [31] and 227 [112] nL/min, respectively; p < 0.001). A nNO level of 77 nL/min had the best discriminative value to differentiate between the two groups. Patients with PCD had a significant higher modified PIDACAR score than patients without PCD (5 2 and 1 1, respectively [p < 0.001]). Using ROC curve analysis, the modified PICADAR score of 2 had the best discriminative value with a sensitivity of 1.00 and a specificity of 0.89. Conclusions Low nNO concentration and the modified PICADAR score are suitable and cheap screening tests for PCD in adults with bronchiectasis.

In Situ Metabolomics in Cancer by Mass Spectrometry Imaging.

Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies.

Position statement on radiopharmaceutical production for clinical trials.

The EU regulation 536/2014 aims to facilitate the experimental use of diagnostic radiopharmaceuticals in particular for GMP requirements and needs to be applied in EU countries. As definitely clarified by this survey, the application is still far from being completed due to national restrictions that are conflicting with the content of the above EU regulation. Although the nuclear medicine centers are obliged to be compliant with national regulatory, national authorities have to be required to work towards full application of the regulation. On the other hand, an update of 536/2014 that includes therapeutic radiopharmaceuticals would also be beneficial to a rational and safe advance of nuclear medicine.

Small RNAs and extracellular vesicles in filarial nematodes: From nematode development to diagnostics.

Parasitic nematodes have evolved sophisticated mechanisms to communicate with their hosts in order to survive and successfully establish an infection. The transfer of RNA within extracellular vesicles (EVs) has recently been described as a mechanism that could contribute to this communication in filarial nematodes. It has been shown that these EVs are loaded with several types of RNAs, including microRNAs, leading to the hypothesis that parasites could actively use these molecules to manipulate host gene expression and to the exciting prospect that these pathways could result in new diagnostic and therapeutic strategies. Here, we review the literature on the diverse RNAi pathways that operate in nematodes and more specifically our current knowledge of extracellular RNA (exRNA) and EVs derived from filarial nematodes in vitro and within their hosts. We further detail some of the issues and questions related to the capacity of RNA-mediated communication to function in parasite-host interactions and the ability of exRNA to enable us to distinguish and detect different nematode parasites in their hosts.

Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience.

Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression.