Search

Abstract Background Ordinal tasks are increasingly used to explore preferences for health states. This study aimed to determine the suitability of two ordinal preference elicitation tasks (discrete choice experiments (DCE) and best-worst scaling (BWS)) for use with children and young people to generate health state utility values. The study explored children’s understanding, the relationship between their age and level of understanding, and how many tasks they felt they could complete. Methods Children aged 11–16 years were recruited from a secondary school in South Yorkshire, UK. Participants were asked to ‘think aloud’ as they completed a computer-based survey that contained both DCE and BWS tasks relating to dental caries (tooth decay) health states. Health states involved descriptions of the impact of tooth decay on children’s daily lives. One-to-one semi-structured interviews were then held with participants, with use of a topic guide. Qualitative data were transcribed verbatim and analysed thematically. Results A total of 33 children (12 male, 21 female) participated, comprising 5–6 children from each school year group. Children expressed a preference for BWS and demonstrated a better understanding of these tasks than DCE. There was no clear relationship between children’s level of understanding and age. Children felt they could manage between 8 and 10 BWS tasks comfortably. Conclusion This study suggests that BWS tasks are the most appropriate type of preference elicitation task to value health states for children and young people aged 11–16 years to complete.

Hand preference in non-human primates has been studied extensively with the aim of understanding the evolution of hemispheric asymmetry and hand preferences in humans. However, the focus has been on hand preferences expressed in adulthood, with a surprising lack of studies on hand preferences in infants and changes that occur during the development of other, potentially associated, asymmetries in the brain and behaviour. This paper reports on the development of hand preference for grasping food and taking it to the mouth in common marmosets. It considers the development of other types of behaviour, such as head cocking and anogenital licking, that parallel and might influence the development of hand preferences during the first months of life. It then discusses behavioural differences between left- and right-handed adult marmosets, including response to novel stimuli, social behaviour and cognitive bias. The need to study the development of hand preferences together with the development of these other expressions of cognitive function is highlighted. The question to be addressed by empirical studies is whether hand preference is a downstream manifestation of the development of hemispheric differences in sensory processing and cognition, or whether it is instrumental in the development of functional differences between the hemispheres. Comparison is made to paw preference and associated behaviour in non-primate species.

Abstract Background Caries Impacts and Experiences Questionnaire for Children (CARIES-QC) is a child-centred caries-specific quality of life measure. This study aimed to select, and validate with children, a classification system for a paediatric condition-specific preference-based measure, based on CARIES-QC. Methods First, a provisional classification system for a preference-based measure based on CARIES-QC was identified using Rasch analysis, psychometric testing, involvement of children and parents, and the developer of CARIES-QC. Second, qualitative, semi-structured ‘think aloud’ validation interviews were undertaken with a purposive sample of children with dental caries. The interviewer aimed to identify whether items were considered important and easily understood, whether any were overlapping and if any excluded items should be reintroduced. Interview recordings were transcribed verbatim and thematic analysis conducted. Results Rasch analysis identified poor item spread for the items ‘cross’ and ‘school’. Items relating to eating were correlated and the better performing items were considered for selection. Children expressed some confusion regarding the items ‘school’ and ‘food stuck’. Parent representatives thought that impacts surrounding toothbrushing (‘brushing’) were encompassed by the item ‘hurt’. Five items were selected from CARIES-QC for inclusion in the provisional classification system; ‘hurt’, ‘annoy’, ‘carefully’, ‘kept awake’ and ‘cried’. Validation interviews were conducted with 20 children aged 5–16 years old. Participants thought the questionnaire was straightforward and covered a range of impacts. Children thought an item about certain foods being ‘hard to eat’ was more relevant than one about having to eat more carefully because of their teeth and so the ‘carefully’ item was replaced with ‘hard to eat’. Conclusion Following child-centred modification, the preliminary five-item classification system is considered valid and suitable for use in a valuation survey. The innovative child-centred methods used to both identify and validate the classification system can be applied in the development of other preference-based measures.

There is a high incidence of tobacco use among intravenous opioid drug users. It is well established that opioids and tobacco smoke induce a degree of immune activation, and recent work suggests that the combination of these drugs promotes further activation of the immune system. Our approach involved the treatment of wild-type mice with cigarette smoke (SM) for a period of eight weeks, and the chronic continuous administration of morphine (M) via mini-pumps for the final four weeks. In an effort to examine the responses of CD4+CD25highCD127low regulatory T (Treg) cells, the major immune suppressive cell type, to the combined chronic administration of SM and M, we determined the frequency of these cells in the spleen, lymph nodes and lungs. Flow cytometric analyses showed that SM and M individually, and the combination (SM + M) have differential effects on the numbers of Treg in the spleen, lymph node, and lung. Either SM or M alone increased Treg cell numbers in the spleen, but SM+M did not. Furthermore, SM + M decreased Treg cell numbers in the lymph node and lung. We then performed RNA-Seq on Treg cells from mice treated with SM, M, or SM + M, and we found that the S + M induced a number of significant changes in the transcriptome, that were not as apparent following treatment with either SM or M alone. This included an activation of TWEAK, PI3K/AKT and OXPHOS pathways and a shift to Th17 immunity. Our results have provided novel insights on tissue Treg cell changes, which we suggest are the result of transcriptomic reprogramming induced by SM, M, and SM + M, respectively. We believe these results may lead to the identification of novel therapeutic targets for suppressing smoke and opioid induced Treg cell impairment.

The application of diffusion theory and Monte Carlo lidar radiative transfer simulations presented in Part I of this series of study suggests that snow depth can be derived from the first-, second- and third-order moments of the lidar backscattering pathlength distribution. These methods are now applied to the satellite ICESat-2 lidar measurements over the Arctic sea ice and land surfaces of Northern Hemisphere. Over the Arctic sea ice, the ICESat-2 retrieved snow depths agree well with co-located IceBridge snow radar measured values with a root-mean-square (RMS) difference of 7.8 cm or 29.2% of the mean snow depth. The terrestrial snow depths derived from ICESat-2 show drastic spatial variation of the snowpack along ICESat-2 ground tracks over the Northern Hemisphere, which are consistent with the University of Arizona (UA) and Canadian Meteorological Centre (CMC) gridded daily snow products. The RMS difference in snow depths between ICESat-2 and UA gridded daily snow products is 14 cm, or 28% of the mean UA snow depth. To better understand these results, we also discuss the possible sources of errors in ICESat-2 derived snow depths, including surface roughness within the laser footprint, atmospheric forward scattering, solar background noise, and detector dark current. Simulation results indicate that the snow depth errors would be less than 5 cm if the standard deviation of pulse spreading due to surface roughness is within 50 cm. Our results demonstrate that the ICESat-2 lidar measurements can be used to reliably derive snow depth, which is a critical geophysical parameter for cryosphere studies including sea ice thickness estimation and also provides important constraints in the modeling of terrestrial hydrological processes.

Snow is a crucial element in the Earth’s system, but snow depth and mass are very challenging to be measured globally. Here, we provide the theoretical foundation for deriving snow depth directly from space-borne lidar (ICESat-2) snow multiple scattering measurements for the first time. First, based on the Monte Carlo lidar radiative transfer simulations of ICESat-2 measurements of 532-nm laser light propagation in snow, we find that the lidar backscattering path length follows Gamma distribution. Next, we derive three simple analytical equations to compute snow depth from the average, second-, and third-order moments of the distribution. As a preliminary application, these relations are then used to retrieve snow depth over the Antarctic ice sheet and the Arctic sea ice using the ICESat-2 lidar multiple scattering measurements. The robustness of this snow depth technique is demonstrated by the agreement of snow depth computed from the three derived relations using both modeled data and ICESat-2 observations.

Background:. Patient expectations before cubital tunnel release (CuTR), a common procedure that leads to incomplete symptom resolution for many patients, are unclear. Study purposes included (1) describing preoperative patient expectations, and (2) identifying factors affecting expectations. Methods:. Included patients underwent isolated unilateral CuTR between 2015 and 2021 at a single tertiary academic medical center. Expectations regarding the level of symptomatic improvement were queried preoperatively. Univariate and multivariable binary logistic regression was performed to determine factors associated with expecting great improvement. Results:. Of the 92 included patients, 43 (47%) patients expected great improvement, whereas 27 (29%), four (4%), and five patients (5%) expected some, little, and no improvement, respectively. The remainder (14%) had no expectations. Multivariable modeling demonstrated that retired or unemployed/disabled work status, and commercial insurance status (versus Medicare or Medicaid) were associated with lower expectations independent of the surgeon, surgical technique, revision versus primary CuTR, preoperative atrophy or constant numbness, diabetes, and all studied demographic factors, including social deprivation. Conclusions:. Roughly half of the patients expect great relief, and a third expect lesser degrees of relief, following CuTR. Preoperative expectations are significantly higher in patients with Medicaid and Medicare insurance, representing an opportunity for education, given the association between public insurance payer status and worse health outcomes in general. Age, BMI, preoperative atrophy and/or numbness, and the presence of medical comorbidities do not influence expectations but have been shown to yield worse outcomes or influence need for revision CuTR, representing an opportunity for intervention to align patient and surgeon expectations.

Summary Objective Left ventricular mass (LVM) is a clinical prognostic indicator of cardiovascular disease. Left ventricular mass is associated with body size (body mass index [BMI], weight, and body surface area [BSA]). This study examined if the association between body size (weight, BMI, and BSA) and LVM is influenced by body composition and cardiorespiratory fitness in adults who are overweight or obese. Methods This study included cross‐sectional baseline data from a randomized clinical trial. Participants included 379 adults (age, 45.6 ± 7.9 y) who were overweight or obese (BMI, 32.4 ± 3.8 kg·m−2). Measures included weight, height, BMI, BSA, body composition, cardiorespiratory fitness, and LVM by cardiac magnetic resonance imaging (CMR). Results Left ventricular mass was positively associated with weight, BMI, BSA, and fitness (P < .0001) and inversely associated with percent body fat (P < .0001). Stepwise multiple regression models showed that body fatness was inversely associated and cardiorespiratory fitness was positively associated with LVM even after considering weight, BMI, or BSA in the analyses. Conclusions These cross‐sectional findings support that in adults who are overweight or obese but otherwise relatively healthy, LVM is associated with both body composition and cardiorespiratory fitness. This may indicate the need to reduce body fatness and improve fitness for patients with obesity to enhance cardiovascular structure and function.

This erratum corrects measurements of the prompt and secondary (from-b).

We analyze the rest-frame near-UV and optical nebular spectra of three z > 7 galaxies from the Early Release Observations taken with the Near-Infrared Spectrograph (NIRSpec) on the James Webb Space Telescope (JWST). These three high- z galaxies show the detection of several strong emission nebular lines, including the temperature-sensitive [O iii ] λ 4363 line, allowing us to directly determine the nebular conditions and abundances for O/H, C/O, and Ne/O. We derive O/H abundances and ionization parameters that are generally consistent with other recent analyses. We analyze the mass–metallicity relationship (i.e., slope) and its redshift evolution by comparing between the three z > 7 galaxies and local star-forming galaxies. We also detect the C iii ] λλ 1907, 1909 emission in a z > 8 galaxy from which we determine the most distant C/O abundance to date. This valuable detection of log(C/O) = −0.83 ± 0.38 provides the first test of C/O redshift evolution out to high redshift. For neon, we use the high-ionization [Ne iii ] λ 3869 line to measure the first Ne/O abundances at z > 7, finding no evolution in this α -element ratio. We explore the tentative detection of [Fe ii ] and [Fe iii ] lines in a z > 8 galaxy, which would indicate a rapid buildup of metals. Importantly, we demonstrate that properly flux-calibrated and higher-S/N spectra are crucial to robustly determine the abundance pattern in z > 7 galaxies with NIRSpec/JWST.

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) requires that several clinical criteria are met, and often relies on the identification of rare hemophagocytic cells in the bone marrow. Given the challenge in making the diagnosis, additional signs of immune dysregulation in the bone marrow would have practical clinical use in cases where overt hemophagocytosis is not seen. We present here a case of secondary HLH in a patient with autoimmune hemolysis ultimately diagnosed as Evans syndrome that initially presented with profound dyserythropoeisis in both the peripheral blood and bone marrow. We also explore an association between dyserythropoeisis and HLH in a series of cases previously seen at our institution.

Results from the successful solenoid-free plasma startup using the method of transient coaxial helicity injection (transient CHI) in the QUEST spherical tokamak (ST) are reported. Unlike previous applications of CHI on HIT-II and on NSTX which required two toroidal insulating breaks to the vacuum vessel, QUEST uses a first of its kind, floating single biased electrode configuration, which does not use such a vacuum break. Instead, the CHI electrode is simply insulated from the outer lower divertor plate support structure. This configuration is much more suitable for implementation in a fusion reactor than the previous configurations. Transient CHI generated toroidal currents of 135 kA were obtained. The toroidal current during the formation of a closed flux configuration was over 50 kA. These results bode well for the application of transient CHI in a new generation of compact high-field STs and tokamaks in which the space for the central solenoid is very restricted.

Studying the galaxies responsible for reionization is often conducted through local reionization-era analogs; however, many of these local analogs are too massive to be representative of the low-mass star-forming galaxies that are thought to play a dominant role in reionization. The local, low-mass dwarf starburst galaxy Pox 186 is one such system with physical conditions representative of a reionization-era starburst galaxy. We present deep ultraviolet (UV) spectroscopy of Pox 186 to study its stellar population and ionization conditions and to compare these conditions to other local starburst galaxies. The new Cosmic Origins Spectrograph data are combined with archival observations to cover ∼1150–2000 Å and allow for an assessment of Pox 186's stellar population, the relative enrichment of C and O, and the escape of ionizing photons. We detect significant Ly α and low-ionization state absorption features, indicative of previously undetected neutral gas in Pox 186. The C/O relative abundance, log(C/O) = −0.62 ± 0.02, is consistent with other low-metallicity dwarf galaxies and suggests a comparable star formation history in these systems. We compare UV line ratios in Pox 186 to those of dwarf galaxies and photoionization models, and we find excellent agreement for the ratios utilizing the intense C iii ], O iii ], and double-peaked C iv lines. However, the UV and optical He ii emission is faint and distinguishes Pox 186 from other local starburst dwarf galaxies. We explore mechanisms that could produce faint He ii , which have implications for the low-mass reionization-era galaxies that may have similar ionization conditions.

Abstract Background The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e.,

Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.

Ultrasonic guided waves offer a convenient and practical approach to structural health monitoring and non-destructive evaluation. A key property of guided waves is the fully defined relationship between central frequency and propagation characteristics (phase velocity, group velocity and wavenumber)—which is described using dispersion curves. For many guided wave-based strategies, accurate dispersion curve information is invaluable, such as group velocity for localisation. From experimental observations of dispersion curves, a system identification procedure can be used to determine the governing material properties. As well as returning an estimated value, it is useful to determine the distribution of these properties based on measured data. A method of simulating samples from these distributions is to use the iterative Markov-Chain Monte Carlo (MCMC) procedure, which allows for freedom in the shape of the posterior. In this work, a scanning-laser Doppler vibrometer is used to record the propagation of Lamb waves in a unidirectional-glass-fibre composite plate, and dispersion curve data for various propagation angles are extracted. Using these measured dispersion curve data, the MCMC sampling procedure is performed to provide a Bayesian approach to determining the dispersion curve information for an arbitrary plate. The distribution of the material properties at each angle is discussed, including the inferred confidence in the predicted parameters. The percentage errors of the estimated values for the parameters were 10–15 points larger when using the most likely estimates, as opposed to calculating from the posterior distributions, highlighting the advantages of using a probabilistic approach.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, it is first demonstrated that advanced biomaterials can be leveraged to boost the effectiveness of SARS‐CoV‐2 protein subunit vaccines. Additionally, it is reported that oxygen is a powerful immunological co‐adjuvant and has an ability to further potentiate vaccine potency. In preclinical studies, mice immunized with an oxygen‐generating coronavirus disease 2019 (COVID‐19) cryogel‐based vaccine (O2‐CryogelVAX) exhibit a robust Th1 and Th2 immune response, leading to a sustained production of highly effective neutralizing antibodies against the virus. Even with a single immunization, O2‐CryogelVAX achieves high antibody titers within 21 days, and both binding and neutralizing antibody levels are further increased after a second dose. Engineering a potent vaccine system that generates sufficient neutralizing antibodies after one dose is a preferred strategy amid vaccine shortage. The data suggest that this platform is a promising technology to reinforce vaccine‐driven immunostimulation and is applicable to current and emerging infectious diseases.

Background:. Carpal tunnel release (CTR) is common, yet patient treatment expectations remain unclear. The primary purpose was to describe patient expectations before CTR. Secondarily, we aimed to identify factors influencing expectations. Methods:. Included patients underwent unilateral or bilateral CTR between 2015 and 2017 at a single academic center. Expectations regarding the level of relief/improvement were queried. Area deprivation index (ADI) was used to measure social deprivation. Univariate and multivariable logistic regression identified factors associated with expecting great relief/improvement. Results:. Of 307 included patients, mean age was 54 ± 16 years and 63% were women. Patients most commonly expected great (58%) or some (23%) relief/improvement. Few patients expected little (3%) or no (4%) relief/improvement, and 13% had no expectations. In the multivariable analysis, male sex, lower social deprivation, and lower BMI were associated with expecting great relief/improvement. Age, surgical technique (open versus endoscopic), use of the operating room versus procedure room, and preoperative factors (constant numbness, weakness/atrophy, duration of symptoms, and QuickDASH) were not associated with expectations. Conclusions:. Most patients expect some to great improvement after CTR. This was independent of several factors with a known association with worse outcomes (advanced age, atrophy/weakness, and constant numbness). Male sex was associated with the expectation of great improvement, in which superior outcomes relative to females have not been borne out in the literature. These findings highlight patient counseling opportunities. The observed association between social deprivation and expectations warrants further investigation, as the socioeconomically disadvantaged experience worse healthcare outcomes in general.

Optimal migration theory is a framework used to evaluate trade-offs associated with migratory strategies. Two strategies frequently considered by migration theory are time minimizing, whereby migration is completed as quickly as possible, and energy minimizing, whereby migration is completed as energetically efficiently as possible. Despite extensive literature dedicated to generating analytical predictions about these migratory strategies, identifying appropriate study systems to empirically test predictions is difficult. Theoretical predictions that compare migratory strategies are qualitative, and empirical tests require that both time-minimizers and energy-minimizers are present in the same population; spring migrating silver-haired (Lasionycteris noctivagans) and hoary bats (Lasiurus cinereus) provide such a system. As both species mate in the fall, spring-migrating males are thought to be energy-minimizers while females benefit from early arrival to summering grounds, and are thought to be time-minimizers. Thermoregulatory expression also varies between species during spring migration, as female silver-haired bats and males of both species use torpor while female hoary bats, which implant embryos earlier, are thought to avoid torpor use which would delay pregnancy. Based on optimal migration theory, we predicted that female silver-haired bats and hoary bats would have increased fuel loads relative to males and the difference between fuel loads of male and female hoary bats would be greater than the difference between male and female silver-haired bats. We also predicted that females of both species would have a greater stopover foraging proclivity and/or assimilate nutrients at a greater rate than males. We then empirically tested our predictions using quantitative magnetic resonance to measure fuel load, δ13C isotope breath signature analysis to assess foraging, and 13C–labeled glycine to provide an indicator of nutrient assimilation rate. Optimal migration theory predictions of fuel load were supported, but field observations did not support the predicted refueling mechanisms, and alternatively suggested a reliance on increased fuel loads via carry-over effects. This research is the first to validate a migration theory prediction in a system of both time and energy minimizers and uses novel methodological approaches to uncover underlying mechanisms of migratory stopover use.

Bifidobacterium animalislactis

OBJECTIVES:. Unbiased global metabolomic profiling has not been used to identify distinct subclasses in patients with early sepsis and sepsis-associated acute respiratory distress syndrome. In this study, we examined whether the plasma metabolome reflects systemic illness in early sepsis and in acute respiratory distress syndrome. DESIGN:. Plasma metabolites were measured in subjects with early sepsis. SETTING:. Patients were admitted from the emergency department to the ICU in a plasma sample collected within 24 hours of ICU admission. Metabolic profiling of 970 metabolites was performed by Metabolon (Durham, NC). Hierarchical clustering and partial least squares discriminant clustering were used to identify distinct clusters among patients with early sepsis and sepsis-associated acute respiratory distress syndrome. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among critically ill patients with early sepsis (n = 197), three metabolically distinct subgroups were identified, with metabolic subtype driven by plasma lipids. Group 1, with 45 subjects (23% of cohort), had increased 60-day mortality (odds ratio, 2; 95% CI, 0.99–4.0; p = 0.04 for group 1 vs all others). This group also had higher rates of vasopressor-dependent shock, acute kidney injury, and met Berlin acute respiratory distress syndrome criteria more often (all p < 0.05). Conversely, metabolic group 3, with 76 subjects (39% of cohort), had the lowest risk of 60-day mortality (odds ratio, 0.44; 95% CI, 0.22–0.86; p = 0.01) and lower rates of organ dysfunction as reflected in a lower Simplified Acute Physiology Score II (p < 0.001). In contrast, global metabolomic profiling did not separate patient with early sepsis with moderate-to-severe acute respiratory distress syndrome (n = 78) from those with sepsis without acute respiratory distress syndrome (n = 75). CONCLUSIONS:. Plasma metabolomic profiling in patients with early sepsis identified three metabolically distinct groups that were characterized by different plasma lipid profiles, distinct clinical phenotypes, and 60-day mortality. Plasma metabolites did not distinguish patients with early sepsis who developed acute respiratory distress syndrome from those who did not.

Weight loss maintenance can be difficult and ultimately unsuccessful, due to psychological, behavioural, social, and physiological influences. The present study investigated three strategies with the potential to improve weight maintenance success: daily weighing, missing an occasional meal, habitually changing high energy foods. The principal aim was to gain an understanding of attitudes to these strategies in participants who had recent experience of weight loss attempts, with or without maintenance. This was a qualitative study involving semi-structured interviews, with 20 participants aged 18–67 (twelve females), analysed using thematic analysis. Most participants disliked daily weighing and missing an occasional meal for long-term maintenance and were concerned about potential negative effects on mental health. All participants had experience of habitual changes to high energy foods and regarded this strategy as obvious and straightforward. Replacement of high energy foods was favoured over elimination. Participants preferred strategies that felt flexible, “normal” and intuitive and disliked those that were thought to have a negative impact on mental health. Further investigation is needed on whether concerns regarding mental health are well founded and, if not, how the strategies can be made more acceptable and useful.

CD4+ regulatory T cells (Tregs) respond to environmental cues to permit or suppress inflammation, and atherosclerosis weakens Treg suppression and promotes plasticity. However, the effects of smoking plus morphine (SM + M) on Treg plasticity remain unknown. To determine whether SM + M promotes Treg plasticity to T helper 17 (Th17) cells, we analyzed the RNA sequencing data from SM, M, and SM + M treated Tregs and performed knowledge-based and IPA analysis. We demonstrated that (1) SM + M, M, and SM upregulated the transcripts of cytokines, chemokines, and clusters of differentiation (CDs) and modulated the transcripts of kinases and phosphatases in Tregs; (2) SM + M, M, and SM upregulated the transcripts of immunometabolism genes, trained immunity genes, and histone modification enzymes; (3) SM + M increased the transcripts of Th17 transcription factor (TF) RORC and Tfh factor CXCR5 in Tregs; M increased the transcripts of T helper cell 1 (Th1) TF RUNX3 and Th1-Th9 receptor CXCR3; and SM inhibited Treg TGIF1 transcript; (4) six genes upregulated in SM + M Tregs were matched with the top-ranked Th17 pathogenic genes; and 57, 39 genes upregulated in SM + M Tregs were matched with groups II and group III Th17 pathogenic genes, respectively; (5) SM + M upregulated the transcripts of 70 IPA-TFs, 11 iTregs-specific TFs, and 4 iTregs-Th17 shared TFs; and (6) SM + M, M, and SM downregulated Treg suppression TF Rel (c-Rel); and 35 SM + M downregulated genes were overlapped with Rel−/− Treg downregulated genes. These results provide novel insights on the roles of SM + M in reprogramming Treg transcriptomes and Treg plasticity to Th17 cells and novel targets for future therapeutic interventions involving immunosuppression in atherosclerotic cardiovascular diseases, autoimmune diseases, transplantation, and cancers.

Nectarines are perishable fruits grown in Southern Europe, valued for their sensorial properties. Chilling is used in the supply chain for Northern European consumers, while Southern European consumers can access fresh, locally grown fruit or cold-stored supermarket fruit. Cold storage and fruit ripening affect texture and flavour. Here a consumer survey and hedonic testing compared the appreciation of nectarines (cv. Big Top) in Italy and at two UK sites (n = 359). Fruit was at the commercial harvest stage, or stored at 1 °C or 5 °C for seven days, then sampled after two days’ (Italy and one UK site) or four days’ (second UK site) ambient recovery. In the consumer survey, the most important factors involved in purchase decision were ripeness, texture, colour, taste and price. Named varieties were more important to Italian than UK respondents, whilst ripeness, price, taste, blemishes, aroma, and ‘best before date’ were more important in the UK. In sensory analyses, fruits at the commercial harvest stage were preferred to those stored at 1 °C. Preference for the 5 °C stored peaches depended on recovery time. Distinct clusters of peach sensorial attributes were positively or negatively linked to hedonic rating. Factors important in purchase decisions did not affect hedonic rating in the tasting.

Cold storage is used to extend peach commercial life, but can affect quality. Quality changes are assessed through the content of nutritionally relevant compounds, aroma, physical characters and/or sensorially. Here, six peach and nectarine cultivars were sampled at commercial harvest and after 7 days of 1 °C storage. A trained panel was used to evaluate sensorial characters, while carotenoids, phenolics, vitamin C, total sugars, and qualitative traits including firmness, titrable acidity and soluble solid content were integrated with volatile organic compound (VOC) analysis previously reported. The different analyses reveal interesting patterns of correlation, and the six cultivars responded differently to cold storage. Sensory parameters were correlated with 64 VOCs and seven intrinsic characters. Acidity, firmness, and 10 VOCs were strongly negatively correlated with harmony and sweetness, but positively correlated with bitterness, astringency, and crunchiness. In contrast, Brix, b-carotene, and six VOCs were positively correlated with harmony and sweetness.

Although plasma electrolyte levels are quickly and precisely regulated in the mammalian cardiovascular system, even small transient changes in K+, Na+, Ca2+, and/or Mg2+ can significantly alter physiological responses in the heart, blood vessels, and intrinsic (intracardiac) autonomic nervous system. We have used mathematical models of the human atrial action potential (AP) to explore the electrophysiological mechanisms that underlie changes in resting potential (Vr) and the AP following decreases in plasma K+, [K+]o, that were selected to mimic clinical hypokalemia. Such changes may be associated with arrhythmias and are commonly encountered in patients (i) in therapy for hypertension and heart failure; (ii) undergoing renal dialysis; (iii) with any disease with acid-base imbalance; or (iv) post-operatively. Our study emphasizes clinically-relevant hypokalemic conditions, corresponding to [K+]o reductions of approximately 1.5 mM from the normal value of 4 to 4.5 mM. We show how the resulting electrophysiological responses in human atrial myocytes progress within two distinct time frames:(i) Immediately after [K+]o is reduced, the K+-sensing mechanism of the background inward rectifier current (IK1) responds. Specifically, its highly non-linear current-voltage relationship changes significantly as judged by the voltage dependence of its region of outward current. This rapidly alters, and sometimes even depolarizes, Vr and can also markedly prolong the final repolarization phase of the AP, thus modulating excitability and refractoriness.(ii) A second much slower electrophysiological response (developing 5–10 minutes after [K+]o is reduced) results from alterations in the intracellular electrolyte balance. A progressive shift in intracellular [Na+]i causes a change in the outward electrogenic current generated by the Na+/K+ pump, thereby modifying Vr and AP repolarization and changing the human atrial electrophysiological substrate.In this study, these two effects were investigated quantitatively, using seven published models of the human atrial AP. This highlighted the important role of IK1 rectification when analyzing both the mechanisms by which [K+]o regulates Vr and how the AP waveform may contribute to “trigger” mechanisms within the proarrhythmic substrate. Our simulations complement and extend previous studies aimed at understanding key factors by which decreases in [K+]o can produce effects that are known to promote atrial arrhythmias in human hearts.

E2F transcription factors are key components of the RB/E2F pathway that, through the action of cyclin-dependent kinases, regulates cell cycle progression in both plants and animals. Moreover, plant and animal E2Fs have also been shown to regulate other cellular functions in addition to cell proliferation. Based on structural and functional features, they can be divided into different classes that have been shown to act as activators or repressors of E2F-dependent genes. Among the first plant E2F factors to be reported, we previously described DcE2F1, an activating E2F which is expressed in cycling carrot (Daucus carota) cells. In this study, we describe the identification of the additional members of the E2F/DP family of D. carota, which includes four typical E2Fs, three atypical E2F/DEL genes, and three related DP genes. Expression analyses of the carrot E2F and DP genes reveal distinctive patterns and suggest that the functions of some of them are not necessarily linked to cell proliferation. DcE2F1 was previously shown to transactivate an E2F-responsive promoter in transient assays but the functional role of this protein in planta was not defined. Sequence comparisons indicate that DcE2F1 could be an ortholog of the AtE2FA factor of Arabidopsis thaliana. Moreover, ectopic expression of the DcE2F1 cDNA in transgenic Arabidopsis plants is able to upregulate AtE2FB and promotes cell proliferation, giving rise to polycotyly with low frequency, effects that are highly similar to those observed when over-expressing AtE2FA. These results indicate that DcE2F1 is involved in the control of cell proliferation and plays important roles in the regulation of embryo and plant development.

Background: Monocyte subsets in humans, i.e., classical (CM), intermediate (IM), and non-classical monocytes (NCM), are thought to differentially contribute to the pathogenesis of atherosclerosis, the leading cause of cardiovascular disease (CVD). However, the association between monocyte subsets and cardiometabolic disorders and CVD is not well-understood. Thus, the aim of the current systematic review and meta-analysis was to evaluate recent findings from clinical studies that examined the association between the distribution of monocyte subsets in subjects with cardiometabolic disorders and CVD compared to healthy controls.Methods: Articles were systematically searched in CINAHL, PubMed and Cochrane Library. Articles were independently screened and selected by two reviewers. Studies that reported the percentage of each monocyte subset were included in the systematic review and meta-analysis. For the meta-analysis, a random-effects model was used to generate pooled standardized mean differences (SMD) between subjects with cardiometabolic disorders and healthy controls.Results: A total of 1,693 articles were screened and 27 studies were selected for qualitative analyses. Among them, six studies were included in the meta-analysis. In total, sample size ranged from 22 to 135 and mean or median age from 22 to 70 years old. We found studies that reported higher percentage and number of IM and/or NCM in subjects with cardiometabolic disorders (9 out of 13 studies) and in subjects with CVD (11 out of 15 studies) compared to healthy controls. In the meta-analysis, the percentage of CM was lower [SMD = −1.21; 95% CI (−1.92, −0.50); P = 0.0009; I2 = 91%] and the percentage of IM [SMD = 0.56; 95% CI (0.23, 0.88); P = 0.0008; I2 = 65%] and NCM [SMD = 1.39; 95% CI (0.59, 2.19); P = 0.0007; I2 = 93%] were higher in subjects with cardiometabolic disorders compared to healthy controls.Conclusions: Individuals with cardiometabolic disorders and CVD may have a higher percentage of IM and NCM than healthy controls. Future studies are needed to evaluate the cause and biological significance of this potential altered distribution of monocyte subsets.

Introduction: Regional differences in activation rates may contribute to the electrical substrates that maintain atrial fibrillation (AF), and estimating them non-invasively may help guide ablation or select anti-arrhythmic medications. We tested whether non-invasive assessment of regional AF rate accurately represents intracardiac recordings.Methods: In 47 patients with AF (27 persistent, age 63 ± 13 years) we performed 57-lead non-invasive Electrocardiographic Imaging (ECGI) in AF, simultaneously with 64-pole intracardiac signals of both atria. ECGI was reconstructed by Tikhonov regularization. We constructed personalized 3D AF rate distribution maps by Dominant Frequency (DF) analysis from intracardiac and non-invasive recordings.Results: Raw intracardiac and non-invasive DF differed substantially, by 0.54 Hz [0.13 – 1.37] across bi-atrial regions (R2 = 0.11). Filtering by high spectral organization reduced this difference to 0.10 Hz (cycle length difference of 1 – 11 ms) [0.03 – 0.42] for patient-level comparisons (R2 = 0.62), and 0.19 Hz [0.03 – 0.59] and 0.20 Hz [0.04 – 0.61] for median and highest DF, respectively. Non-invasive and highest DF predicted acute ablation success (p = 0.04).Conclusion: Non-invasive estimation of atrial activation rates is feasible and, when filtered by high spectral organization, provide a moderate estimate of intracardiac recording rates in AF. Non-invasive technology could be an effective tool to identify patients who may respond to AF ablation for personalized therapy.

Objectives: Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders of connective tissue that cause skeletal fragility and extra-skeletal manifestations. Classically, four different types of OI were distinguished. Type 5 OI was added due to its distinct clinical and radiographic features. In 2012, two independent groups identified a recurrent heterozygous c.-14C>T mutation in IFITM5 as the responsible genetic change for this type of OI. To our knowledge, cervical kyphosis has not been identified in the literature as a finding in type 5 OI patients. This is a retrospective review of a cohort of patients with type 5 OI and a description of associated cervical spine deformity. Methods: After institutional review board approval, a retrospective review identified 13 patients with type 5 OI. Clinical, radiologic, and genetic data from 2002 to 2020 were reviewed. Results: We identified 13 patients with clinical diagnosis of type 5 OI. Twelve had molecular confirmation and the classic IFITM5, c.14C>T gene mutation was identified. The remaining individual did not undergo genetic testing. Dentinogenesis imperfecta was observed in one patient, while blue sclerae or hearing loss were not present. All patients had at least one fracture and four underwent intramedullary rodding. Radiologic features included subphyseal metaphyseal radiodense line in 12/13 patients (92%), interosseous membrane calcification in seven of 13 patients (54%) (more commonly noted in the upper extremities), and hypertrophic callus in six of 13 patients (46%). Thoracolumbar spinal deformities were seen in six of 13 patients (46%) with two of these individuals requiring surgery. Cervical kyphosis was noted in nine of 13 individuals (69%) ranging in age from 3 months to 22 years. Anterior wedging of the cervical vertebral bodies was noted in the absence of any fractures. Six of nine individuals demonstrated listhesis of C2-C3 or C3-C4 segment. Magnetic resonance imaging studies were performed and reviewed in patients with cervical kyphosis and subluxation; three patients showed narrowing of spinal canal without cervical cord compression and one asymptomatic patient showed impingement of the spinal cord. Conclusions: Cervical kyphosis appears to be a common feature of type 5 OI. It can be a presenting and apparently life-long association and does not appear to be caused by vertebral body fractures. Evaluation for cervical kyphosis should be performed in patients with a suspected or confirmed diagnosis of type 5 OI. Furthermore, if cervical kyphosis is noted in an individual with OI, type 5 OI should be considered.Level of evidence: IV.