Engineering a dysbiotic biofilm model for testing root caries interventions through microbial modulation.

BACKGROUND: This study aimed to engineer and optimise a dysbiotic biofilm model to develop in vitro root caries for investigating microbial modulation strategies. The model involved growing complex biofilms from a saliva inoculum collected from four volunteers using two strategies. In the first strategy ("pre-treatment strategy"), bovine root slabs were used, and two natural compounds were incorporated at time 0 of the 10-day biofilm experiment, which included sucrose cycles mimicking the cariogenic environment. In the second strategy ("post-treatment strategy"), mature biofilms were grown in a modified Calgary biofilm device coated with collagen and hydroxyapatite for 7 days and then were exposed to the same natural compounds. The metatranscriptome of each biofilm was then determined and analysed. Collagenase activity was examined, and the biofilms and dentine were imaged using confocal and scanning electron microscopy (SEM). Mineral loss and lesion formation were confirmed through micro-computed tomography (µ-CT). RESULTS: The pH confirmed the cariogenic condition. In the metatranscriptome, we achieved a biofilm compositional complexity, showing a great diversity of the metabolically active microbiome in both pre- and post-treatment strategies, including reads mapped to microorganisms other than bacteria, such as archaea and viruses. Carbohydrate esterases had increased expression in the post-treated biofilms and in samples without sugar cycles, while glucosyltransferases were highly expressed in the presence of sucrose cycles. Enrichment for functions related to nitrogen compound metabolism and organic cyclic component metabolism in groups without sucrose compared to the sucrose-treated group. Pre-treatment of the roots with cranberry reduced microbial viability and gelatinase (but not collagenase) activity (p < 0.05). SEM images showed the complexity of biofilms was maintained, with a thick extracellular polysaccharides layer. CONCLUSIONS: This root caries model was optimized to produce complex cariogenic biofilms and root caries-like lesions, and could be used to test microbial modulation in vitro. Pre-treatments before biofilm development and cariogenic challenges were more effective than post-treatments. The clinical significance lies in the potential to apply the findings to develop varnish products for post-professional tooth prophylaxis, aiming at implementing a strategy for dysbiosis reversal in translational research. Video Abstract.

Calcium-Based Imaging of the Spine at Dual-Layer CT and Evaluation of Vertebral Fractures in Multiple Myeloma.

PURPOSE: To evaluate the prediction of vertebral fractures in plasma cell dyscrasias using dual-layer CT (DLCT) with quantitative assessment of conventional CT image data (CI), calcium suppressed image data (CaSupp), and calculation of virtual calcium-only (VCa) image data. MATERIAL AND METHODS: Patients (n = 81) with the diagnosis of a plasma cell dyscrasia and whole-body DLCT at the time of diagnosis and follow-up were retrospectively enrolled. CI, CaSupp25, and CaSupp100 were quantitatively analyzed using regions of interest in the lumbar vertebral bodies and fractured vertebral bodies on baseline or follow-up imaging. VCa were calculated by subtraction (CaSupp100-CaSupp25), delineating bone only. Logistic regression analyses were performed to assess the possibility of imminent spine fractures. RESULTS: In 24 patients, new vertebral fractures were observed in the follow-up imaging. The possibility of new vertebral fractures was significant for baseline assessment of CT numbers in CI, CaSupp25, and VCa (p = 0.01, respectively), with a higher risk for new fractures in the case of lower CT numbers in CI (Odds ratio = [0.969; 0.994]) and VCa (Odds ratio = [0.978; 0.995]) and in the case of higher CT numbers in CaSupp 25 (Odds ratio 1.015 [1.006; 1.026]). Direct model comparisons implied that CT numbers in CaSupp 25 and VCa might show better fracture prediction than those in CI (R2 = 0.18 both vs. 0.15; AICc = 91.95, 91.79 vs. 93.62), suggesting cut-off values for CI at 103 HU (sensitivity: 54.2%; specificity: 82.5; AUC: 0.69), for VCa at 129 HU (sensitivity: 41.7%; specificity: 94.7; AUC: 0.72). CONCLUSIONS: Quantitative assessment with CaSupp and calculation of VCa is feasible to predict the vertebral fracture risk in MM patients. DLCT may prove useful in detecting imminent fractures.

Rho-dependent transcriptional switches regulate the bacterial response to cold shock.

Binding of the bacterial Rho helicase to nascent transcripts triggers Rho-dependent transcription termination (RDTT) in response to cellular signals that modulate mRNA structure and accessibility of Rho utilization (Rut) sites. Despite the impact of temperature on RNA structure, RDTT was never linked to the bacterial response to temperature shifts. We show that Rho is a central player in the cold-shock response (CSR), challenging the current view that CSR is primarily a posttranscriptional program. We identify Rut sites in 5'-untranslated regions of key CSR genes/operons (cspA, cspB, cspG, and nsrR-rnr-yjfHI) that trigger premature RDTT at 37°C but not at 15°C. High concentrations of RNA chaperone CspA or nucleotide changes in the cspA mRNA leader reduce RDTT efficiency, revealing how RNA restructuring directs Rho to activate CSR genes during the cold shock and to silence them during cold acclimation. These findings establish a paradigm for how RNA thermosensors can modulate gene expression.

Defect-Driven MoS2 Nanosheets toward Enhanced Sensing Sensitivity.

In this study, S-deficient MoS2 was prepared using proton irradiation and then applied as sensing materials for the detection of NO2 gas. First, bulk MoS2 was treated by ultrasonics to produce 2D nanosheets of MoS2, which were subsequently bombarded by a flux of high-energy protons, resulting in the appearance of structural defects throughout MoS2. The proton fluxes were adjusted to different densities of 1 × 1011, 1 × 1012, 1 × 1013, and 1 × 1014 ions/cm2. The effects of proton irradiation on the defects, also referred to as atomic vacancies, were systematically investigated using Raman measurements to locate the E1 2g and A1g modes and X-ray photoelectron spectroscopy to determine the binding energy of Mo 3d and S 2p orbitals. It was revealed that the density of proton irradiation greatly affects the degree of S atom vacancies in irradiated MoS2, while also enhancing the n-type semiconducting behaviors of MoS2. The vacancy-rich MoS2 was then demonstrated to exhibit a higher response to NO2 gas compared to that of nonirradiated MoS2, showing a 4-fold increase in response within a concentration range from 1 to 20 ppm. These results could pave the way for new approaches to fabricating sensing materials.

Pectin as a Biomaterial in Regenerative Endodontics-Assessing Biocompatibility and Antibacterial Efficacy against Common Endodontic Pathogens: An In Vitro Study.

Regenerative endodontics (REP) is a new clinical modality aiming to regenerate damaged soft and hard dental tissues, allowing for root completion in young adults' teeth. Effective disinfection is crucial for REP success, but commonly used antimicrobials often harm the niche dental pulp stem cells (DPSCs). To our knowledge, this is the first study to explore the biocompatibility and antimicrobial potential of pectin as a potential natural intracanal medicament for REPs. Low methoxyl commercial citrus pectin (LM) (pectin CU701, Herbstreith&Fox.de) was used in all experiments. The pectin's antibacterial activity against single species biofilms (E. faecalis and F. nucleatum) was assessed using growth curves. The pectin's antimicrobial effect against mature dual-species biofilm was also evaluated using confocal laser scanning microscopy (CLSM) after 30 min and 7 days of treatment. The DPSC biocompatibility with 2% and 4% w/v of the pectin coatings was evaluated using live/dead staining, LDH, and WST-1 assays. Pectin showed a concentration-dependent inhibitory effect against single-species biofilms (E. faecalis and F. nucleatum) but failed to disrupt dual-species biofilm. Pectin at 2% w/v concentration proved to be biocompatible with the HDPSCs. However, 4% w/v pectin reduced both the viability and proliferation of the DPSCs. Low concentration (2% w/v) pectin was biocompatible with the DPSCs and showed an antimicrobial effect against single-species biofilms. This suggests the potential for using pectin as an injectable hydrogel for clinical applications in regenerative endodontics.

Feasibility of Reduced Iodine Loads for Vascular Assessment Prior to Transcatheter Aortic Valve Implantation (TAVI) Using Spectral Detector CT.

Reduced iodine loads for computed tomography (CT)-based vascular assessment prior to transcatheter aortic valve implantation (TAVI) may be feasible in conjunction with a spectral detector CT scanner. This prospective single-center study considered 100 consecutive patients clinically referred for pre-TAVI CT. They were examined on a dual-layer detector CT scanner to obtain an ECG-gated cardiac scan and a non-ECG-gated aortoiliofemoral scan. Either a standard contrast media (SCM) protocol using 80 mL Iohexol 350 mgI/mL (iodine load: 28 gI) or a body-mass-index adjusted reduced contrast media (RCM) protocol using 40-70 mL Iohexol 350 mgI/mL (iodine load: 14-24.5 gI) were employed. Conventional images and virtual monoenergetic images at 40-80 keV were reconstructed. A threshold of 250 HU was set for sufficient attenuation along the arterial access pathway. A qualitative assessment used a five-point Likert scale. Sufficient attenuation in the thoracic aorta was observed for all patients in both groups using conventional images. In the abdominal, iliac, and femoral segments, sufficient attenuation was observed for the majority of patients when using virtual monoenergetic images (SCM: 96-100% of patients, RCM: 88-94%) without statistical difference between both groups. Segments with attenuation measurements below the threshold remained qualitatively assessable as well. Likert scores were 'excellent' for virtual monoenergetic images 50 keV and 55 keV in both groups (RCM: 1.2-1.4, SCM: 1.2-1.3). With diagnostic image quality maintained, it can be concluded that reduced iodine loads of 14-24.5 gI are feasible for pre-TAVI vascular assessment on a spectral detector CT scanner.

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial.

BACKGROUND: Inflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients. METHODS: This study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines. RESULTS: During the study's follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1ß, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients. CONCLUSION: AD-MSCs represent a potential intervention to prevent age-related inflammation in patients. TRIAL REGISTRATION: ClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020.

Botulinum toxin A injection for post-stroke upper limb spasticity and rehabilitation practices from centers across Asian countries.

Purpose: Describe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings. Methods: Subgroup analysis of a prospective, observational study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described. Results: Overall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (p < 0.001). The majority (96.1%) of Asian patients were rated as having improved. Conclusion: In the Asian treatment setting, BoNT-A demonstrated a clinically significant effect on goal attainment for the real-life management of upper limb spasticity following stroke.

BMI-Adapted Double Low-Dose Dual-Source Aortic CT for Endoleak Detection after Endovascular Repair: A Prospective Intra-Individual Diagnostic Accuracy Study.

PURPOSE: To assess the diagnostic accuracy of BMI-adapted, low-radiation and low-iodine dose, dual-source aortic CT for endoleak detection in non-obese and obese patients following endovascular aortic repair. METHODS: In this prospective single-center study, patients referred for follow-up CT after endovascular repair with a history of at least one standard triphasic (native, arterial and delayed phase) routine CT protocol were enrolled. Patients were divided into two groups and allocated to a BMI-adapted (group A, BMI < 30 kg/m2; group B, BMI ≥ 30 kg/m2) double low-dose CT (DLCT) protocol comprising single-energy arterial and dual-energy delayed phase series with virtual non-contrast (VNC) reconstructions. An in-patient comparison of the DLCT and routine CT protocol as reference standard was performed regarding differences in diagnostic accuracy, radiation dose, and image quality. RESULTS: Seventy-five patients were included in the study (mean age 73 ± 8 years, 63 (84%) male). Endoleaks were diagnosed in 20 (26.7%) patients, 11 of 53 (20.8%) in group A and 9 of 22 (40.9%) in group B. Two radiologists achieved an overall diagnostic accuracy of 98.7% and 97.3% for endoleak detection, with 100% in group A and 95.5% and 90.9% in group B. All examinations were diagnostic. The DLCT protocol reduced the effective dose from 10.0 ± 3.6 mSv to 6.1 ± 1.5 mSv (p < 0.001) and the total iodine dose from 31.5 g to 14.5 g in group A and to 17.4 g in group B. CONCLUSION: Optimized double low-dose dual-source aortic CT with VNC, arterial and delayed phase images demonstrated high diagnostic accuracy for endoleak detection and significant radiation and iodine dose reductions in both obese and non-obese patients compared to the reference standard of triple phase, standard radiation and iodine dose aortic CT.

Exploring fishers' pro-environmental behavioral intention and support for policies to combat marine litter in Vietnam.

This study applies Value-Belief-Norm (VBN) theory to investigate fishers' pro-environmental behavioral intention and their support for policies to reduce marine litter. While pro-environmental behavioral intention is often associated with personal environmental intention at the household level, policy support represents their support for government action at the political level. Therefore, we examine whether fishers are willing to engage in both of these dimensions. Data from 369 Vietnamese fishers are analyzed using structural equation modeling with FIMIX-PLS and PLS-POS. The results show that the sequence of values, beliefs, and personal norms can explain the fishers' pro-environmental behavioral intention and their support for policies addressing marine litter. Two segments of the fishers are detected from the sample with different perspectives of engagement intention. Fishers in segment 1 placed great emphasis on the consequences of marine litter on fishing activities as a motivator for their responsible actions. Meanwhile, fishers in segment 2 express pro-environmental engagement intention driven by the concern about responsibility and moral obligation. A binary logistic regression indicates that the risks of marine litter on fishing activity can provide the explanations for the differences between them. Our findings highlight both fishers' pro-environmental behavior and policy support as important strategies for dealing with marine litter in fisheries. If implemented simultaneously, they hold promise to alleviate the environmental and economic impact of marine litter in Vietnam.

The antimicrobial activity of theobromine against cariogenic microbes: an in vitro pilot study.

OBJECTIVE: This pilot study aimed to compare the antimicrobial effect of theobromine, sodium fluoride, and a theobromine-sodium fluoride combination against the following caries-associated bacteria: Streptococcus mutans and Actinomyces naeslundii. METHODOLOGY: Antimicrobial susceptibility was tested via the broth microdilution method, with suspensions cultured on each microbe's respective selective media. Shapiro-Wilk's was completed and all the data showed normality (p > 0.05), and One-way ANOVA was applied to infer the significant differences in the viable counts between the groups. RESULTS: All experimental conditions for both S. mutans and A. naeslundii groups resulted in a significantly lower bacterial abundance in comparison to the control medium, without any active antimicrobial agent (p < 0.001). There was no significant difference in viable count between the theobromine, fluoride, or combination groups against either microbe (p > 0.05). CONCLUSION: Theobromine's antimicrobial activity against S. mutans and A. naeslundii was found similar to that of fluoride, whether used independently or in combination. Further testing of theobromine is necessary to assess its role as an alternative anticaries agent.

Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

Sweet Orange Juice Processing By-Product Extracts: A Caries Management Alternative to Chlorhexidine.

Dental caries is one of the most prevalent chronic diseases globally in both children and adults. This study investigated the potential of industrial sweet orange waste extracts (ISOWE) as a substitute for chlorhexidine (CHX) in managing dental caries. First, the cytotoxicity of ISOWE (40, 80, 120 mg/mL) and CHX (0.1 and 0.2%) on buccal epithelial cells was determined. ISOWE exhibited no overall toxicity, whereas CHX strongly affected cell viability. The combination of ISOWE and CHX significantly enhanced cell proliferation compared to CHX alone. Next, the antimicrobial efficacy of ISOWE, CHX, and their combination was assessed against a 7-day complex biofilm model inoculated with oral samples from human volunteers. CHX exhibited indiscriminate antimicrobial action, affecting both pathogenic and health-associated oral microorganisms. ISOWE demonstrated lower antimicrobial efficacy than CHX but showed enhanced efficacy against pathogenic species while preserving the oral microbiome's balance. When applied to a cariogenic biofilm, the combined treatment of ISOWE with 0.1% CHX showed similar efficacy to 0.2% CHX treatment alone. Overall, the findings suggest that ISOWE is a promising natural anti-cariogenic agent with lower toxicity and enhanced selectivity for pathogenic species compared to CHX.

Hub genes and pathways related to caries-free dental biofilm: clinical metatranscriptomic study.

OBJECTIVE: This study aimed to evaluate the microbial functional profile of biofilms related to caries-free (CF, n = 6) and caries-arrested (CI, n = 3) compared to caries-active (CA, n = 5) individuals. MATERIALS AND METHODS: A metatranscriptomic was performed in supragingival biofilm from different clinical conditions related to caries or health. Total RNA was extracted and cDNAs were obtained and sequenced (Illumina HiSeq3000). Trimmed data (SortMeRNA) were submitted to the SqueezeMeta pipeline in the co-assembly mode for functional analysis and further differential gene expression analysis (DESeq2) and weighted gene co-expression network analysis (WCGNA) to explore and identify gene modules related to these clinical conditions. RESULTS: A total of 5303 genes were found in the metatranscriptomic analysis. A co-expression network identified the most relevant modules strongly related to specific caries status. Correlation coefficients were calculated between the eigengene modules and the clinical conditions (CA, CI, and CF) discriminating multiple modules. CA and CI showed weak correlation coefficient strength across the modules, while the CF condition presented a very strong positive correlation coefficient (r = 0.9, p value = 4 × 10-9). Pearson's test was applied to further analyze the module membership and gene significance in CF conditions, and the most relevant were HSPA1s-K03283, Epr- K13277, and SLC1A-K05613. Gene Ontology (GO) shows important bioprocesses, such as two-component system, fructose and mannose metabolism, pentose and glucuronate interconversions, and flagellar assembly (p-adjust < 0.05). The ability to use different carbohydrates, integrate multiple signals, swarm, and bacteriocin production are significant metabolic advantages in the oral environment related to CF. CONCLUSIONS: A distinct functional health profile could be found in CF, where co-occurring genes can act in different pathways at the same time. Genes HSPA1s, Epr, and SLC1A may be appointed as potential biomarkers for caries-free biofilms. CLINICAL RELEVANCE: Potential biomarkers for caries-free biofilms could contribute to the knowledge of caries prevention and control.

Biofilm dysbiosis and caries activity: a surface or an individual issue?

OBJECTIVE: This study aimed to analyze the functional profile of supragingival biofilm from sound (CAs), active (CAa), and inactive (CAi) enamel caries lesions from caries-active individuals to provide insights into the diversity of biological processes regarding biofilm dysbiosis. METHODOLOGY: A metatranscriptome analysis was performed in biofilm samples collected from five caries-active individuals. Total RNA was extracted, and the microbial cDNAs were obtained and sequenced (Illumina HiSeq3000). Trimmed data were submitted to the SqueezeMeta pipeline in the co-assembly mode for functional analysis and further differential gene expression analysis (DESeq2). RESULTS: Bioinformatics analysis of mRNAs revealed a similar functional profile related to all analyzed conditions (CAa, CAi, and CAs). However, active and inactive surfaces share up-regulated genes (gtsA; qrtT; tqsA; pimB; EPHX1) related to virulence traits that were not overrepresented in sound surfaces. From a functional perspective, what matters most is the individual carious status rather than the surface condition. Therefore, pooling samples from various sites can be carried out using naturally developed oral biofilms but should preferably include carious surfaces. CONCLUSION: Metatranscriptome data from subjects with caries activity have shown that biofilms from sound, arrested, and active lesions are similar in composition and function.

Acid tolerance of Lactobacillus spp. on root carious lesions: A complex and multifaceted response.

Lactobacillus spp. are acidogenic and aciduric bacteria and are among the main cariogenic microorganisms associated with the carious process. OBJECTIVE: This study aimed to identify genes involved in the acid-tolerance of Lactobacillus spp. and potential functions attributed to these genes within the metatranscriptome of sound root surfaces and carious root surfaces. DESIGN: Genomic libraries were built from mRNA isolated from the biofilm samples (10 from sound root and 9 from carious root using Illumina HiSeq 2500). Reads generated by RNA-seq were mapped against 162 oral microbial genomes and genes potentially related to acid tolerance were manually extracted from the Lactobacillus spp. genomes using L. paracasei ATCC 344 as reference genome. The R package DESeq2 was used to calculate the level of differential gene expression between those two clinical conditions. RESULTS: Fifteen Lactobacillus spp. genomes were identified and a total of 653 acid tolerance genes were overexpressed in carious root surfaces. Multiple functions, as translation, ribosomal structure and biogenesis, transport of nucleotides and amino acids, are involved in Lactobacillus spp. acid tolerance. Species-specific functions also seem to be related to the fitness of Lactobacillus spp. in acidified environments such as that of the cariogenic biofilm associated with carious root lesions. CONCLUSIONS: The response of Lactobacillus spp. to an acidic environment is complex and multifaceted. This finding suggests several possible avenues for further research into the adaptive mechanisms of these bacteria.

Metal Artifact Reduction in Photon-Counting Detector CT: Quantitative Evaluation of Artifact Reduction Techniques.

OBJECTIVES: With the introduction of clinical photon-counting detector computed tomography (PCD-CT) and its novel reconstruction techniques, a quantitative investigation of different acquisition and reconstruction settings is necessary to optimize clinical acquisition protocols for metal artifact reduction. MATERIALS AND METHODS: A multienergy phantom was scanned on a clinical dual-source PCD-CT (NAEOTOM Alpha; Siemens Healthcare GmbH) with 4 different central inserts: water-equivalent plastic, aluminum, steel, and titanium. Acquisitions were performed at 120 kVp and 140 kVp (CTDIvol 10 mGy) and reconstructed as virtual monoenergetic images (VMIs; 110-150 keV), as T3D, and with the standard reconstruction "none" (70 keV VMI) using different reconstruction kernels (Br36, Br56) and with as well as without iterative metal artifact reduction (iMAR). Metal artifacts were quantified, calculating relative percentages of metal artifacts. Mean CT numbers of an adjacent water-equivalent insert and different tissue-equivalent inserts were evaluated, and eccentricity of metal rods was measured. Repeated-measures analysis of variance was performed for statistical analysis. RESULTS: Metal artifacts were most prevalent for the steel insert (12.6% average artifacts), followed by titanium (4.2%) and aluminum (1.0%). The strongest metal artifact reduction was noted for iMAR (with iMAR: 1.4%, without iMAR: 10.5%; P < 0.001) or VMI (VMI: 110 keV 2.6% to 150 keV 3.3%, T3D: 11.0%, and none: 16.0%; P < 0.001) individually, with best results when combining iMAR and VMI at 110 keV (1.2%). Changing acquisition tube potential (120 kV: 6.6%, 140 kV: 5.2%; P = 0.33) or reconstruction kernel (Br36: 5.5%, Br56: 6.4%; P = 0.17) was less effective. Mean CT numbers and standard deviations were significantly affected by iMAR (with iMAR: -3.0 ± 21.5 HU, without iMAR: -8.5 ± 24.3 HU; P < 0.001), VMI (VMI: 110 keV -3.6 ± 21.6 HU to 150 keV -1.4 ± 21.2 HU, T3D: -11.7 ± 23.8 HU, and none: -16.9 ± 29.8 HU; P < 0.001), tube potential (120 kV: -4.7 ± 22.8 HU, 140 kV: -6.8 ± 23.0 HU; P = 0.03), and reconstruction kernel (Br36: -5.5 ± 14.2 HU, Br56: -6.8 ± 23.0 HU; P < 0.001). Both iMAR and VMI improved quantitative CT number accuracy and metal rod eccentricity for the steel rod, but iMAR was of limited effectiveness for the aluminum rod. CONCLUSIONS: For metal artifact reduction in PCD-CT, a combination of iMAR and VMI at 110 keV demonstrated the strongest artifact reduction of the evaluated options, whereas the impact of reconstruction kernel and tube potential was limited.

Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.

Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using physical working capacity (power output) at a heart rate of 150 beats/min (PWC150) as an indicator of submaximal exercise capacity in subjects of the HERITAGE Family Study, we have undertaken multi-omics and in silico explorations of the underlying biology of PWC150 and its response to 20 wk of endurance training. Our goal was to illuminate the biological processes and identify panels of genes associated with human variability in intrinsic PWC150 (iPWC150) and its trainability (dPWC150). Our bioinformatics approach was based on a combination of genome-wide association, skeletal muscle gene expression, and plasma proteomics and metabolomics experiments. Genes, proteins, and metabolites showing significant associations with iPWC150 or dPWC150 were further queried for the enrichment of biological pathways. We compared genotype-phenotype associations of emerging candidate genes with reported functional consequences of gene knockouts in mouse models. We investigated the associations between DNA variants and multiple muscle and cardiovascular phenotypes measured in HERITAGE subjects. Two panels of prioritized genes of biological relevance to iPWC150 (13 genes) and dPWC150 (6 genes) were identified, supporting the hypothesis that genes and pathways associated with iPWC150 are different from those underlying dPWC150. Finally, the functions of these genes and pathways suggested that human variation in submaximal exercise capacity is mainly driven by skeletal muscle morphology and metabolism and red blood cell oxygen-carrying capacity.NEW & NOTEWORTHY Multi-omics and in silico explorations of the genes and underlying biology of submaximal exercise capacity and its response to 20 wk of endurance training were undertaken. Prioritized genes were identified: 13 genes for variation in submaximal exercise capacity in the sedentary state and 5 genes for the response level to endurance training, with no overlap between them. Genes and pathways associated with submaximal exercise capacity in the sedentary state are different from those underlying trainability.

Light Enhancement of Green Up-Conversion Emission from Er-Doped Silica Microspheres by Carbon Quantum Dot Coatings.

Combination of high quality cavity such as glass microsphere and emitting nano-particle coating layers can create novel strongly emitting devices. Herein, we demonstrate an erbium-doped silica microsphere coated by dual-emission carbon quantum dots, which have the sizes of 3-5 nm, emitting green up-conversion with narrow line-width green light at wavelength of 537 nm. The dual-emission carbon quantum dots fabricated by hydrothermal process and have luminescent emission wavelengths in the range of 410-550 nm. The carbon quantum dot coated erbium silica microsphere is pumped at wavelength of 976 nm through the optical fibre on which microsphere attached on the tip. The dual-emission carbon quantum dot layers attributed to the strong green up-conversion light enhancement similar coated noble metallic thin films, however the light enhancement from dual-emission carbon quantum dot coated erbium silica microsphere depended on the thickness of coating layers. This result is useful for making visible emitting micro-devices and photonic integrated circuits.