Preventive and restorative alternatives to caries by irradiation: a scoping review.

PURPOSE: This study is to conduct a comprehensive scoping review to map scientific evidence and clarify concepts regarding the commonly recommended preventive and restorative dental treatments for patients diagnosed with head and neck cancer (HNC) and subjected to radiotherapy. MATERIAL AND METHODS: This systematic scoping review was performed under the PRISMA-ScR guidelines. The study's experimental design was registered in the Open Science Framework. In vitro studies that evaluated preventive and restorative dental treatment over 50 Gy radiation doses were included. The search was conducted in November 2023 in five electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase) without language or date restriction. A search strategy was applied based on keywords, MeSh terms, or synonyms. A descriptive analysis was conducted. RESULTS: A total of 49 studies, out of 3679 original articles identified, were included and reviewed. Of the included studies, three evaluated saliva stimulants and 35 evaluated fluoride-based preventive materials: gel (n = 18) toothpaste (n = 11) mouth rinse (n = 8) and varnish (n = 5) while 14 evaluated restorative materials: resin composite (n = 12) glass ionomer cement (n = 6) and amalgam (n = 1) Of those studies, 36 were clinical trials and 13 were in vitro studies. CONCLUSION: Fluoride gel was the most frequently recommended preventive material for preventing radiation caries with supportive clinical evidence. Resin composite and glass ionomer were the most frequently used restorative materials, respectively. However, there is not yet clinical evidence to support the use of resin composite in irradiated teeth.

Effects of simulation-based flipped classroom in developing head and neck examination skills in dental students.

OBJECTIVES: To evaluate the effectiveness of a simulation-based flipped classroom in developing dental students' head and neck examination skills. METHODS: Second-year dental students (n = 118) participated in a simulation-based flipped classroom experience. A pre-class recorded lecture and video were posted online one week before the simulation date. In class, students completed a pre-quiz assessing pre-class coursework understanding of head and neck examination content. Then, students attended a question-and-answer session before the patient simulation. A formative assessment of head and neck examination simulation on a patient in the clinic was completed. Lastly, students completed an in-class post-quiz assessing understanding of head and neck examination content after the simulation, classroom simulation discussion, and open-response survey. RESULTS: Student post-quiz scores were significantly higher than pre-quiz scores, with an average improvement of 4.8 ± 7.2 percentage points. There was no difference between male and female improvement in scores. Student survey responses indicated that students liked combining simulation and flipped classroom methodology, flexibility with their schedules, learning at their pace, and opportunities for a deeper level of learning. Students reported wanting more practice sessions for their technical skills and more accessibility to faculty. CONCLUSIONS: According to this study's results, students had significantly higher post-quiz scores than pre-quiz scores and reported positive perceptions of this combined teaching technique. A simulation-based flipped classroom might be an effective teaching approach for developing head and neck examination skills that can be applied at other dental facilities with potentially similar results.

Effect of educational intervention on computer-aided-design and computer-aided-manufacturing technology to preclinical dental students.

INTRODUCTION: This study evaluated the effectiveness of a video presentation instruction compared to the prevailing traditional lecture provided in the preclinical classroom when introducing computer-aided design/computer-aided manufacturing (CAD/CAM) technology. MATERIALS AND METHODS: This study was conducted as a controlled educational trial (single-blind) on 120 first-year dental students. Students were assigned to two learning groups: the control (n = 60, traditional lecture) and the intervention (n = 60, video presentation). Both groups completed a self-efficacy scale (SES) survey before instruction. Then, the intervention group actively participated in a one-session video presentation while the control group was given a traditional lecture. After the presentations, student knowledge was assessed with a hands-on simulated exercise that was scored out of 60 points. At last, students completed a post-instruction student perception and attitude (SPA) survey. Inferential hypothesis testing was conducted with two-sample t-tests, and significance was defined as p ≤ .05. RESULTS: There were no significant differences in the student pre-instruction SES scores between the control and intervention groups. After the video learning, CAD/CAM knowledge application during the hands-on simulated exercise showed significantly higher results in the intervention group as the assessment scores from the intervention group averaged 13.6 ± 2.0 points higher than the control group (p < .001). The results from the post-instruction SPA survey showed no statistically significant difference between groups. CONCLUSION: With the video presentation technique, our first-year dental students were able to greatly enhance their CAD/CAM application skills. The results from this study could be applied at other dental educational institutions with potential similar outcomes.

Filtered back projection vs. iterative reconstruction for CBCT: effects on image noise and processing time.

OBJECTIVES: To assess the effect of standard filtered back projection (FBP) and iterative reconstruction (IR) methods on CBCT image noise and processing time (PT), acquired with various acquisition parameters with and without metal artefact reduction (MAR). METHODS: CBCT scans using the Midmark EIOS unit of a human mandible embedded in soft tissue equivalent material with and without the presence of an implant at mandibular first molar region were acquired at various acquisition settings (milliamperages [4mA-14mA], FOV [5 × 5, 6 × 8, 9 × 10 cm], and resolutions [low, standard, high] and reconstructed using standard FBP and IR, and with and without MAR. The processing time was recorded for each reconstruction. ImageJ was used to analyze specific axial images. Radial transaxial fiducial lines were created relative to the implant site. Standard deviations of the gray density values (image noise) were calculated at fixed distances on the fiducial lines on the buccal and lingual aspects at specific axial levels, and mean values for FBP and IR were compared using paired t-tests. Significance was defined as p < 0.05. RESULTS: The overall mean for image noise (± SD) for FBP was 198.65 ± 55.58 and 99.84 ± 16.28 for IR. IR significantly decreased image noise compared to FBP at all acquisition parameters (p < 0.05). Noise reduction among different scanning protocols ranged between 29.7% (5 × 5 cm FOV) and 58.1% (5mA). IR increased processing time by an average of 35.1 s. CONCLUSIONS: IR significantly reduces CBCT image noise compared to standard FBP without substantially increasing processing time.

Dynamic growth QTL action in diverse light environments: characterization of light regime-specific and stable QTL in Arabidopsis.

Plant growth is a complex process affected by a multitude of genetic and environmental factors and their interactions. To identify genetic factors influencing plant performance under different environmental conditions, vegetative growth was assessed in Arabidopsis thaliana cultivated under constant or fluctuating light intensities, using high-throughput phenotyping and genome-wide association studies. Daily automated non-invasive phenotyping of a collection of 382 Arabidopsis accessions provided growth data during developmental progression under different light regimes at high temporal resolution. Quantitative trait loci (QTL) for projected leaf area, relative growth rate, and PSII operating efficiency detected under the two light regimes were predominantly condition-specific and displayed distinct temporal activity patterns, with active phases ranging from 2 d to 9 d. Eighteen protein-coding genes and one miRNA gene were identified as potential candidate genes at 10 QTL regions consistently found under both light regimes. Expression patterns of three candidate genes affecting projected leaf area were analysed in time-series experiments in accessions with contrasting vegetative leaf growth. These observations highlight the importance of considering both environmental and temporal patterns of QTL/allele actions and emphasize the need for detailed time-resolved analyses under diverse well-defined environmental conditions to effectively unravel the complex and stage-specific contributions of genes affecting plant growth processes.

Dynamics of Maize Vegetative Growth and Drought Adaptability Using Image-Based Phenotyping Under Controlled Conditions.

Changes in climate are likely to have a negative impact on water availability and soil fertility in many maize-growing agricultural areas. The development of high-throughput phenotyping platforms provides a new prospect for dissecting the dynamic complex plant traits such as abiotic stress tolerance into simple components. The growth phenotypes of 20 maize (Zea mays L.) inbred lines were monitored in a non-invasive way under control, nitrogen, and water limitation as well as under combined nitrogen and water stress using an automated phenotyping system in greenhouse conditions. Thirteen biomass-related and morphophysiological traits were extracted from RGB images acquired at 33 time points covering developmental stages from leaf count 5 at the first imaging date to leaf count 10-13 at the final harvest. For these traits, genetic differences were identified and dynamic developmental trends during different maize growth stages were analyzed. The difference between control and water stress was detectable 3-10 days after the beginning of stress depending on the genotype, while the effect of limited nitrogen supply only induced subtle phenotypic effects. Phenotypic traits showed different response dynamics as well as multiple and changing interaction patterns with stress progression. The estimated biovolume, leaf area index, and color ratios were found to be stress-responsive at different stages of drought stress progression and thereby represent valuable reference indicators in the selection of drought-adaptive genotypes. Furthermore, genotypes could be grouped according to two typical growth dynamic patterns in water stress treatments by c-means clustering analysis. Inbred lines with high drought adaptability across time and development were identified and could serve as a basis for designing novel genotypes with desired, stage-specific growth phenotypes under water stress through pyramiding. Drought recovery potential may play an equal role as drought tolerance in plant drought adaptation.

The Development and Implementation of Preventive Medicine Resident Rotations in a Shelter Serving Asylum-Seekers at the US-Mexico Border.

Asylum-seekers present to the US-Mexico border with a variety of acute health needs. In December 2018, the County of San Diego Health and Human Services Agency partnered with the University of California, San Diego to provide health screenings to asylum-seekers at a humanitarian shelter administered by Jewish Family Services. The assessments screened for communicable diseases and acute conditions. Preventive medicine residents in the HRSA-funded UCSD-SDSU (University of California, San Diego-San Diego State University) Residency were trained to become an integral part of the program. Training included cultural competency, public health interface, protocol development and implementation, interdisciplinary teamwork, and quality improvement. Over 18 months, nearly 20000 asylum-seekers were screened, which allowed for the detection of an imported influenza outbreak and prevented any major public health incidents or medical errors. This health screening program for asylum-seekers provided an important experience for preventive medicine trainees. In turn, preventive medicine and other trainees were valuable contributors to the program.

Temporal dynamics of QTL effects on vegetative growth in Arabidopsis thaliana.

We assessed early vegetative growth in a population of 382 accessions of Arabidopsis thaliana using automated non-invasive high-throughput phenotyping. All accessions were imaged daily from 7 d to 18 d after sowing in three independent experiments and genotyped using the Affymetrix 250k SNP array. Projected leaf area (PLA) was derived from image analysis and used to calculate relative growth rates (RGRs). In addition, initial seed size was determined. The generated datasets were used jointly for a genome-wide association study that identified 238 marker-trait associations (MTAs) individually explaining up to 8% of the total phenotypic variation. Co-localization of MTAs occurred at 33 genomic positions. At 21 of these positions, sequential co-localization of MTAs for 2-9 consecutive days was observed. The detected MTAs for PLA and RGR could be grouped according to their temporal expression patterns, emphasizing that temporal variation of MTA action can be observed even during the vegetative growth phase, a period of continuous formation and enlargement of seemingly similar rosette leaves. This indicates that causal genes may be differentially expressed in successive periods. Analyses of the temporal dynamics of biological processes are needed to gain important insight into the molecular mechanisms of growth-controlling processes in plants.

Image Phenotyping of Spring Barley (Hordeum vulgare L.) RIL Population Under Drought: Selection of Traits and Biological Interpretation.

Image-based phenotyping is a non-invasive method that permits the dynamic evaluation of plant features during growth, which is especially important for understanding plant adaptation and temporal dynamics of responses to environmental cues such as water deficit or drought. The aim of the present study was to use high-throughput imaging in order to assess the variation and dynamics of growth and development during drought in a spring barley population and to investigate associations between traits measured in time and yield-related traits measured after harvesting. Plant material covered recombinant inbred line population derived from a cross between European and Syrian cultivars. After placing the plants on the platform (28th day after sowing), drought stress was applied for 2 weeks. Top and side cameras were used to capture images daily that covered the visible range of the light spectrum, fluorescence signals, and the near infrared spectrum. The image processing provided 376 traits that were subjected to analysis. After 32 days of image phenotyping, the plants were cultivated in the greenhouse under optimal watering conditions until ripening, when several architecture and yield-related traits were measured. The applied data analysis approach, based on the clustering of image-derived traits into groups according to time profiles of statistical and genetic parameters, permitted to select traits representative for inference from the experiment. In particular, drought effects for 27 traits related to convex hull geometry, texture, proportion of brown pixels and chlorophyll intensity were found to be highly correlated with drought effects for spike traits and thousand grain weight.

Inducible aging in Hydra oligactis implicates sexual reproduction, loss of stem cells, and genome maintenance as major pathways.

Freshwater polyps of the genus Hydra do not age. However, temperature stress induces aging and a shift from reproduction by asexual budding to sexual gamete production in a cold-sensitive (CS) strain of H. oligactis. We sequenced the transcriptome of a male CS strain before and after this life history shift and compared changes in gene expression relative to those seen in a cold-resistant (CR) strain that does not undergo a life history shift in response to altered temperature. We found that the switch from non-aging asexual reproduction to aging and sexual reproduction involves upregulation of genes not only involved in gametogenesis but also genes involved in cellular senescence, apoptosis, and DNA repair accompanied by a downregulation of genes involved in stem cell maintenance. These results suggest that aging is a byproduct of sexual reproduction-associated cellular reprogramming and underscore the power of these H. oligactis strains to identify intrinsic mechanisms of aging.

mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging.

Cerebrovascular dysfunction and cognitive decline are highly prevalent in aging, but the mechanisms underlying these impairments are unclear. Cerebral blood flow decreases with aging and is one of the earliest events in the pathogenesis of Alzheimer's disease (AD). We have previously shown that the mechanistic/mammalian target of rapamycin (mTOR) drives disease progression in mouse models of AD and in models of cognitive impairment associated with atherosclerosis, closely recapitulating vascular cognitive impairment. In the present studies, we sought to determine whether mTOR plays a role in cerebrovascular dysfunction and cognitive decline during normative aging in rats. Using behavioral tools and MRI-based functional imaging, together with biochemical and immunohistochemical approaches, we demonstrate that chronic mTOR attenuation with rapamycin ameliorates deficits in learning and memory, prevents neurovascular uncoupling, and restores cerebral perfusion in aged rats. Additionally, morphometric and biochemical analyses of hippocampus and cortex revealed that mTOR drives age-related declines in synaptic and vascular density during aging. These data indicate that in addition to mediating AD-like cognitive and cerebrovascular deficits in models of AD and atherosclerosis, mTOR drives cerebrovascular, neuronal, and cognitive deficits associated with normative aging. Thus, inhibitors of mTOR may have potential to treat age-related cerebrovascular dysfunction and cognitive decline. Since treatment of age-related cerebrovascular dysfunction in older adults is expected to prevent further deterioration of cerebral perfusion, recently identified as a biomarker for the very early (preclinical) stages of AD, mTOR attenuation may potentially block the initiation and progression of AD.

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra.

Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within 3 months. This phenotype is not observed in the cold-resistant strain Ho_CR To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduced in aging Ho_CS but sustained in non-aging Ho_CR We also identified a deficient autophagy in Ho_CS epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly inducible autophagy flux upon proteasome inhibition. In the non-aging H. vulgaris animals, the blockade of autophagy by knocking down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.

Image-Derived Traits Related to Mid-Season Growth Performance of Maize Under Nitrogen and Water Stress.

Phenotypic measurements under controlled cultivation conditions are essential to gain a mechanistic understanding of plant responses to environmental impacts and thus for knowledge-based improvement of their performance under natural field conditions. Twenty maize inbred lines (ILs) were phenotyped in response to two levels of water and nitrogen supply (control and stress) and combined nitrogen and water deficit. Over a course of 5 weeks (from about 4-leaf stage to the beginning of the reproductive stage), maize phenology and growth were monitored by using a high-throughput phenotyping platform for daily acquisition of images in different spectral ranges. The focus of the present study is on the measurements taken at the time of maximum water stress (for traits that reflect plant physiological properties) and at the end of the experiment (for traits that reflect plant architectural and biomass-related traits). Twenty-five phenotypic traits extracted from the digital image data that support biological interpretation of plant growth were selected for their predictive value for mid-season shoot biomass accumulation. Measured fresh and dry weights after harvest were used to calculate various indices (water-use efficiency, physiological nitrogen-use efficiency, specific plant weight) and to establish correlations with image-derived phenotypic features. Also, score indices based on dry weight were used to identify contrasting ILs in terms of productivity and tolerance to stress, and their means for image-derived and manually measured traits were compared. Color-related traits appear to be indicative of plant performance and photosystem II operating efficiency might be an importance physiological parameter of biomass accumulation, particularly under severe stress conditions. Also, genotypes showing greater leaf area may be better adapted to abiotic stress conditions.

Genetic diversity for nitrogen use efficiency in Arabidopsis thaliana.

MAIN CONCLUSION: The plasticity of plant growth response to differing nitrate availability renders the identification of biomarkers difficult, but allows access to genetic factors as tools to modulate root systems to a wide range of soil conditions. Nitrogen availability is a major determinant of crop yield. While the application of fertiliser substantially increases the yield on poor soils, it also causes nitrate pollution of water resources and high costs for farmers. Increasing nitrogen use efficiency in crop plants is a necessary step to implement low-input agricultural systems. We exploited the genetic diversity present in the worldwide Arabidopsis thaliana population to study adaptive growth patterns and changes in gene expression associated with chronic low nitrate stress, to identify biomarkers associated with good plant performance under low nitrate availability. Arabidopsis accessions were grown on agar plates with limited and sufficient supply of nitrate to measure root system architecture as well as shoot and root fresh weight. Differential gene expression was determined using Affymetrix ATH1 arrays. We show that the response to differing nitrate availability is highly variable in Arabidopsis accessions. Analyses of vegetative shoot growth and root system architecture identified accession-specific reaction modes to cope with limited nitrate availability. Transcription and epigenetic factors were identified as important players in the adaption to limited nitrogen in a global gene expression analysis. Five nitrate-responsive genes emerged as possible biomarkers for NUE in Arabidopsis. The plasticity of plant growth in response to differing nitrate availability in the substrate renders the identification of morphological and molecular features as biomarkers difficult, but at the same time allows access to a multitude of genetic factors which can be used as tools to modulate and adjust root systems to a wide range of soil conditions.

Lifelong reduction in complex IV induces tissue-specific metabolic effects but does not reduce lifespan or healthspan in mice.

Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1-/- mice. The lack of deleterious phenotypes in Surf1-/- mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1-/- vs. Surf1+/+ mice despite substantial decreases in COX activity (22%-87% across tissues). Dietary restriction (DR) increased median lifespan in both Surf1+/+ and Surf1-/- mice (36% and 19%, respectively). We measured gene expression, metabolites, and targeted expression of key metabolic proteins in adipose tissue, liver, and brain in Surf1+/+ and Surf1-/- mice. Gene expression was differentially regulated in a tissue-specific manner. Many proteins and metabolites are downregulated in Surf1-/- adipose tissue and reversed by DR, while in brain, most metabolites that changed were elevated in Surf1-/- mice. Finally, mitochondrial unfolded protein response (UPRmt )-associated proteins were not uniformly altered by age or genotype, suggesting the UPRmt is not a key player in aging or in response to reduced COX activity. While the changes in gene expression and metabolism may represent compensatory responses to mitochondrial stress, the important outcome of this study is that lifespan and healthspan are not compromised in Surf1-/- mice, suggesting that not all mitochondrial deficiencies are a critical determinant of lifespan.

Sex Differences in Aging: Genomic Instability.

Aging is characterized by decreasing physiological integration, reduced function, loss of resilience, and increased risk of death. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist. While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal. Among fruit flies, nematodes, and mice, sex differences in lifespan vary depending on strain and treatment. In this review, we focus on sex differences in age-related alterations in DNA damage and mutation rates, telomere attrition, epigenetics, and nuclear architecture. We find that robust sex differences exist, eg, the higher incidence of DNA damage in men compared to women, but sex differences are not often conserved between species. For most mechanisms reviewed here, there are insufficient data to make a clear determination regarding the impact of sex, largely because sex differences have not been analyzed. Overall, our findings reveal an urgent need for well-designed studies that explicitly examine sex differences in molecular drivers of aging.

Sco2 deficient mice develop increased adiposity and insulin resistance.

Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex IV) in the mitochondrial respiratory electron chain. Mutations in genes responsible for the assembly of COX are associated with Leigh syndrome, cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in humans. Previous studies have shown that mice lacking the COX assembly protein Surf1 (Surf1-/- mice) paradoxically show a number of beneficial metabolic phenotypes including increased insulin sensitivity, upregulation of mitochondrial biogenesis, induction of stress response pathways and increased lifespan. To determine whether these effects are specific to the Surf1 mutation or a more general effect of reduced COX activity, we asked whether a different mutation causing reduced COX activity would have similar molecular and physiologic changes. Sco2 knock-in/knock-out (KI/KO) mice in which one allele of the Sco2 gene that encodes a copper chaperone required for COX activity is deleted and the second allele is mutated, have previously been shown to be viable despite a 30-60% reduction in COX activity. In contrast to the Surf1-/- mice, we show that Sco2 KI/KO mice have increased fat mass, associated with reduced ß-oxidation and increased adipogenesis markers, reduced insulin receptor beta (IR-ß levels in adipose tissue, reduced muscle glucose transporter 4 (Glut4) levels and a impaired response to the insulin tolerance test consistent with insulin resistance. COX activity and protein are reduced approximately 50% in adipose tissue from the Sco2 KI/KO mice. Consistent with the increase in adipose tissue mass, the Sco2 KI/KO mice also show increased hepatosteatosis, elevated serum and liver triglyceride and increased serum cholesterol levels compared to wild-type controls. In contrast to the Surf1-/- mice, which show increased mitochondrial number, upregulation of the mitochondrial unfolded protein response (UPRMT) pathway and no significant change in mitochondrial respiration in several tissues, Sco2 KI/KO mice do not upregulate the UPRMT, and tissue oxygen consumption and levels of several proteins involved in mitochondrial function are reduced in adipose tissue compared to wild type mice. Thus, the metabolic effects of the Sco2 and Surf1-/- mutations are opposite, despite comparable changes in COX activity, illuminating the complex impact of mitochondrial dysfunction on physiology and pointing to an important role for complex IV in regulating metabolism.

Impact of tofacitinib treatment on human B-cells in vitro and in vivo.

B-cells are pivotal to the pathogenesis of rheumatoid arthritis and tofacitinib, a JAK inhibitor, is effective and safe in its treatment. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain. Despite extensive data on T-lymphocytes, the impact of tofacitinib on B-lymphocytes is poorly understood. In this study we assessed the effect of tofacitinib on B-lymphocyte differentiation and function. Tofacitinib treatment strongly impaired in vitro plasmablast development, immunoglobulin secretion and induction of B-cell fate determining transcription factors, Blimp-1, Xbp-1, and IRF-4, in naïve B-cells. Interestingly, class switch and activation-induced cytidine deaminase (AICDA) induction was only slightly reduced in activated naïve B-cells. The effect of tofacitinib on plasmablast formation, immunoglobulin secretion and proliferation was less profound, when peripheral blood B-cells, including not only naïve but also memory B-cells, were stimulated. In line with these in vitro results, the relative distribution of B-cell populations remained stable in tofacitinib treated patients. Nevertheless, a temporary increase in absolute B-cell numbers was observed 6-8 weeks after start of treatment. In addition, B-cells isolated from tofacitinib treated patients responded rapidly to in vitro activation. We demonstrate that tofacitinib has a direct impact on human naïve B-lymphocytes, independently from its effect on T-lymphocytes, by impairing their development into plasmablasts and immunoglobulin secretion. The major effect of tofacitinib on naïve B-lymphocyte development points to the potential inability of tofacitinib-treated patients to respond to novel antigens, and suggests planning vaccination strategies prior to tofacitinib treatment.

A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated.

Lifespan provides a discrete metric that is intuitively appealing and the assumption has been that healthspan is extended concomitant with lifespan. Medicine has been more successful at extending life than preserving health during aging. Interventions that extend lifespan in model organisms do not always result in a corresponding increase in healthspan, suggesting that lifespan and healthspan may be uncoupled. To understand how interventions that extend life affect healthspan, we need measures that distinguish between young and old animals. Here we measured age-related changes in healthspan in male and female C57BL/6JNia mice assessed at 4 distinct ages (4 months, 20 months, 28 months and 32 months). Correlations between health parameters and age varied. Some parameters show consistent patterns with age across studies and in both sexes, others changed in one sex only and others showed no significant differences in mice of different ages. Few correlations existed among health assays, suggesting that physiological function in domains we assessed change independently in aging mice. With one exception, health parameters were not significantly associated with an increased probability of premature death. Our results show the need for more robust measures of murine health and suggest a potential disconnect between health and lifespan in mice.

Quantitative monitoring of Arabidopsis thaliana growth and development using high-throughput plant phenotyping.

With the implementation of novel automated, high throughput methods and facilities in the last years, plant phenomics has developed into a highly interdisciplinary research domain integrating biology, engineering and bioinformatics. Here we present a dataset of a non-invasive high throughput plant phenotyping experiment, which uses image- and image analysis- based approaches to monitor the growth and development of 484 Arabidopsis thaliana plants (thale cress). The result is a comprehensive dataset of images and extracted phenotypical features. Such datasets require detailed documentation, standardized description of experimental metadata as well as sustainable data storage and publication in order to ensure the reproducibility of experiments, data reuse and comparability among the scientific community. Therefore the here presented dataset has been annotated using the standardized ISA-Tab format and considering the recently published recommendations for the semantical description of plant phenotyping experiments.