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Elevated numbers of atherogenic lipoproteins (apoB) predict the incidence of type 2 diabetes (T2D). We reported that this may be mediated via the activation of the NLRP3 inflammasome, as low-density lipoproteins (LDL) induce interleukin-1 beta (IL-1β) secretion from human white adipose tissue (WAT) and macrophages. However, mitigating nutritional approaches remained unknown. We tested whether omega-3 eicosapentaenoic and docosahexaenoic acids (EPA and DHA) treat LDL-induced upregulation of WAT IL-1β-secretion and its relation to T2D risk factors. Twelve-week intervention with EPA and DHA (2.7 g/day, Webber Naturals) abolished baseline group-differences in WAT IL-1β-secretion between subjects with high-apoB (N = 17) and low-apoB (N = 16) separated around median plasma apoB. Post-intervention LDL failed to trigger IL-1β-secretion and inhibited it in lipopolysaccharide-stimulated WAT. Omega-3 supplementation also improved β-cell function and postprandial fat metabolism in association with higher blood EPA and mostly DHA. It also blunted the association of WAT NLRP3 and IL1B expression and IL-1β-secretion with multiple cardiometabolic risk factors including adiposity. Ex vivo, EPA and DHA inhibited WAT IL-1β-secretion in a dose-dependent manner. In conclusion, EPA and DHA treat LDL-induced upregulation of WAT NLRP3 inflammasome/IL-1β pathway and related T2D risk factors. This may aid in the prevention of T2D and related morbidities in subjects with high-apoB. Clinical Trail Registration ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects with High Number of Particles That Carry "Bad Cholesterol" in the Blood – Full Text View - ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Tropical glaciers in the central Andes are vital water resources and crucial climate indicators, currently undergoing rapid retreat. However, understanding their vulnerability to the combined effects of persistent warming, the El Niño and La Niña climate phenomena, and interannual fluctuations remains limited. Here, we automate the mapping of key mass balance parameters on the Quelccaya Ice Cap (QIC) in Peru, one of the largest tropical ice caps. Using Landsat's near-infrared (NIR) band, we analyze snow cover area (SCA) and total area (TA) and calculate the accumulation area ratio (AAR) and equilibrium-line altitude (ELA) over nearly 40 years (1985–2023). Between 1985 and 2022, the QIC lost ∼58 % and ∼37 % of its SCA and TA, respectively. We show that the QIC's reduction in SCA and rise in ELA are exacerbated by El Niño events, which are strongly correlated with the preceding wet season's Oceanic Niño Index (ONI). Further, expansion in the QIC's SCA is observed during all La Niña years, except during the 2021–2022 La Niña. Although this is a singular event, it could indicate a weakened ability for SCA recovery and an accelerated decline in the future, primarily driven by anthropogenic warming. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric emergency department (ED) guidelines emphasize timely identification of delirium. This article updates previous diagnostic accuracy systematic reviews of history, physical examination, laboratory testing, and ED screening instruments for the diagnosis of delirium as well as test–treatment thresholds for ED delirium screening. Methods: We conducted a systematic review to quantify the diagnostic accuracy of approaches to identify delirium. Studies were included if they described adults aged 60 or older evaluated in the ED setting with an index test for delirium compared with an acceptable criterion standard for delirium. Data were extracted and studies were reviewed for risk of bias. When appropriate, we conducted a meta‐analysis and estimated delirium screening thresholds. Results: Full‐text review was performed on 55 studies and 27 were included in the current analysis. No studies were identified exploring the accuracy of findings on history or laboratory analysis. While two studies reported clinicians accurately rule in delirium, clinician gestalt is inadequate to rule out delirium. We report meta‐analysis on three studies that quantified the accuracy of the 4 A's Test (4AT) to rule in (pooled positive likelihood ratio [LR+] 7.5, 95% confidence interval [CI] 2.7–20.7) and rule out (pooled negative likelihood ratio [LR−] 0.18, 95% CI 0.09–0.34) delirium. We also conducted meta‐analysis of two studies that quantified the accuracy of the Abbreviated Mental Test‐4 (AMT‐4) and found that the pooled LR+ (4.3, 95% CI 2.4–7.8) was lower than that observed for the 4AT, but the pooled LR− (0.22, 95% CI 0.05–1) was similar. Based on one study the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) is the superior instrument to rule in delirium. The calculated test threshold is 2% and the treatment threshold is 11%. Conclusions: The quantitative accuracy of history and physical examination to identify ED delirium is virtually unexplored. The 4AT has the largest quantity of ED‐based research. Other screening instruments may more accurately rule in or rule out delirium. If the goal is to rule in delirium then the CAM‐ICU or brief CAM or modified CAM for the ED are superior instruments, although the accuracy of these screening tools are based on single‐center studies. To rule out delirium, the Delirium Triage Screen is superior based on one single‐center study. [ABSTRACT FROM AUTHOR]

We present a three-photon based fluorescence readout method where the strength of the fluorescence scales with the strength of the radio-frequency field being applied. We compare this method to conventional three-photon electromagnetically induced transparency (EIT) and electromagnetically induced absorption (EIA). Our demonstrated three-photon EIA/EIT sensitivity in the collinear three-photon Cesium system is the best reported to date at roughly 30 (same units). The fluorescence is nearly fourfold better in sensitivity compared to EIA/EIT readout. [ABSTRACT FROM AUTHOR]

The number of Arctic glaciers with direct, long-term measurements of mass balance is limited. Here we used satellite-based observations of the glacier snowline altitude (SLA), the location of the transition between snow cover and ice late in the summer, to approximate the position of the equilibrium-line altitude (ELA), a variable important for mass balance assessment and for understanding the response of glaciers to climate change. We mapped the snowline (SL) on a subset of 269 land-terminating glaciers above 60° N latitude in the latest available summer, clear-sky Landsat satellite image between 1984 and 2022. The mean SLA was extracted using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM). We compared the remotely observed SLA observations with available long-term field-based measurements of ELA and with ERA5-Land reanalysis climate data. Over the last 4 decades, Arctic glacier SLAs have risen an average of ∼152 m (3.9±0.4 m yr -1 ; R2=0.74 , p<0.001), with a corresponding summer (June, July, August) temperature shift of +1.2 °C at the glacier locations. This equates to a 127±5 m shift per 1 °C of summer warming. However, we note that the effect of glacier surface thinning could bias our estimates of SLA rise by up to ∼1 m yr -1 , a significant fraction (∼25 %) of the overall rate of change, and thus should be interpreted as a maximum constraint. Along with warming, we observe an overall decrease in snowfall, an increase in rainfall, and a decrease in the total number of days in which the mean daily temperature is less than or equal to 0 °C. Glacier SLA is most strongly correlated with the number of freezing days, emphasizing the dual effect of multi-decadal trends in mean annual temperature on both ablation (increasing melt) and accumulation processes (reducing the number of days in which snow can fall). Although we find evidence for a negative morpho-topographic feedback that occurs as glaciers retreat to higher elevations, we show that more than 50 % of the glaciers studied here could be entirely below the late-summer SLA by 2100, assuming the pace of global warming and the mean rate of SLA rise are maintained. [ABSTRACT FROM AUTHOR]

In this foreword to the Special Issue "Nonlinear dynamics and game-theoretical modeling in economics and finance" we review the contributions in the issue highlighting the economic results and the connections with aspects of dynamic analysis. Indeed, the common theme of the contributions is the focus on system dynamics and the latest analytical techniques. This issue is devoted to celebrating the 70th birthday of Professor Laura Gardini, who inspired a generation of scholars in the study of discrete-time systems and global methods of analysis. [ABSTRACT FROM AUTHOR]

Tropical glaciers are essential water resources in the central Andes as vital water resources and crucial climate indicators, currently undergoing rapid retreat. However, understanding their vulnerability to the combined effects of persistent warming, short-term climate phenomena, and interannual fluctuations remains limited. Here we automate mapping of key mass balance parameters on the Quelccaya Ice Cap (QIC), the world's largest tropical ice cap. Using Landsat's near-infrared (NIR) band, we analyze snow cover area (SCA) and total area (TA) and calculate the Accumulation Area Ratio (AAR) and Equilibrium Line Altitude (ELA) over nearly 40 years (1985–2023). Between 1985 and 2022, the QIC lost ~46 % and ~34 % of its SCA and TA, respectively. We show that the QIC's loss in SCA and rise in ELA are exacerbated by El Niño events, which are strongly correlated to the preceding wet season's Ocean Niño Index (ONI). We observe lower levels of correlation to more recent El Niño events as anthropogenic climatic impacts overwhelm the natural forcing and continue to exacerbate loss at the QIC. [ABSTRACT FROM AUTHOR]

The number of Arctic glaciers with direct, long–term measurements of mass balance is limited. Here we used satellite–based observations of the glacier snowline altitude (SLA), the location of the transition between snow cover and ice late in the summer, to approximate the position of the equilibrium line altitude (ELA)–a parameter important for mass balance assessment and for understanding the response of glaciers to climate change. We mapped the snowline (SL) on a subset of 269 land–terminating glaciers above 60 °N latitude in the latest available summer, clear–sky Landsat satellite image between 1984 and 2022. The mean SLA was extracted using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM). We compare remotely–observed SLA observations with available long–term field–based measurements of ELA and with ERA5–Land reanalysis climate data. Over the last four decades, Arctic glacier SLAs have risen an average of ~152 m (3.9±0.4 m yr–1; R2=0.74, p<0.001), with a corresponding summer (June, July, August) temperature shift of +1.2 °C at the glacier locations. This equates to a 127±5 m shift per 1 °C of summer warming. However, along with warming, we observe an overall decrease in snowfall, an increase in rainfall, and a decrease in the total number of days in which the mean daily temperature is less than or equal to 0 °C. Glacier SLA is most strongly correlated with the number of freezing days, emphasizing the dual effect of multi–decadal trends in mean annual temperature on both ablation (increasing melt) and accumulation processes (reducing the number of days in which snow can fall). Although we find evidence for a negative morpho–topographic feedback that occurs as glaciers retreat to higher elevations, we show that more than 50 % of the glaciers studied here could be entirely below the SLA by 2100, assuming the pace of global warming and the mean rate of SLA rise is maintained. [ABSTRACT FROM AUTHOR]

The number of Arctic glaciers with direct, long-term measurements of mass balance is limited. Here we used satellite-based observations of the glacier snowline altitude (SLA), the location of the transition between snow cover and ice late in the summer, to approximate the position of the equilibrium line altitude (ELA)-a parameter important for mass balance assessment and for understanding the response of glaciers to climate change. We mapped the snowline (SL) on a subset of 269 land-terminating glaciers above 60 °N latitude in the latest available summer, clear-sky Landsat satellite image between 1984 and 2022. The mean SLA was extracted using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM). We compare remotely-observed SLA observations with available long-term field-based measurements of ELA and with ERA5-Land reanalysis climate data. Over the last four decades, Arctic glacier SLAs have risen an average of ~152 m (3.9±0.4 m yr-1; R2=0.74, p<0.001), with a corresponding summer (June, July, August) temperature shift of +1.2 °C at the glacier locations. This equates to a 127±5 m shift per 1 °C of summer warming. However, along with warming, we observe an overall decrease in snowfall, an increase in rainfall, and a decrease in the total number of days in which the mean daily temperature is less than or equal to 0 °C. Glacier SLA is most strongly correlated with the number of freezing days, emphasizing the dual effect of multi-decadal trends in mean annual temperature on both ablation (increasing melt) and accumulation processes (reducing the number of days in which snow can fall). Although we find evidence for a negative morpho-topographic feedback that occurs as glaciers retreat to higher elevations, we show that more than 50% of the glaciers studied here could be entirely below the SLA by 2100, assuming the pace of global warming and the mean rate of SLA rise is maintained. [ABSTRACT FROM AUTHOR]

The remarkable capabilities of generative artificial intelligence and large language models (LLMs) such as ChatGPT have delighted users around the world. Educators have regarded these tools as either a cause for great concern, an opportunity to educate students on cutting-edge technology, or often some combination of the two. Throughout the Fall 2023 semester, we explored the use of ChatGPT (and Bard, among other LLMs) in a graduate level numerical and statistical methods course for PhD-level bioengineers. In this article we share examples of this ChatGPT content, our observations on what worked best in our course, and speculate on how bioengineering students may be best served by this technology in the future. [ABSTRACT FROM AUTHOR]

The genesis of a mature complement of neurons is thought to require, at least in part, precursor cell lineages in which neural progenitors have distinct identities recognized by exclusive expression of one or a few molecular markers. Nevertheless, limited progenitor types distinguished by specific markers and lineal progression through such subclasses cannot easily yield the magnitude of neuronal diversity in most regions of the nervous system. The late Verne Caviness, to whom this edition of Developmental Neuroscience is dedicated, recognized this mismatch. In his pioneering work on the histogenesis of the cerebral cortex, he acknowledged the additional flexibility required to generate multiple classes of cortical projection and interneurons. This flexibility may be accomplished by establishing cell states in which levels rather than binary expression or repression of individual genes vary across each progenitor's shared transcriptome. Such states may reflect local, stochastic signaling via soluble factors or coincidence of cell surface ligand/receptor pairs in subsets of neighboring progenitors. This probabilistic, rather than determined, signaling could modify transcription levels via multiple pathways within an apparently uniform population of progenitors. Progenitor states, therefore, rather than lineal relationships between types may underlie the generation of neuronal diversity in most regions of the nervous system. Moreover, mechanisms that influence variation required for flexible progenitor states may be targets for pathological changes in a broad range of neurodevelopmental disorders, especially those with polygenic origins. [ABSTRACT FROM AUTHOR]

Objective: Specialty care may improve diabetic foot ulcer outcomes. Medically underserved populations receive less specialty care. We aimed to determine the association between specialty care and ulcer progression, major amputation, or death. If a beneficial association is found, increasing access to specialty care might help advance health equity. Research design and methods: We retrospectively analyzed a cohort of Wisconsin and Illinois Medicare patients with diabetic foot ulcers (n = 55,409), stratified by ulcer severity (i.e., early stage, osteomyelitis, or gangrene). Within each stratum, we constructed Kaplan-Meier curves for event-free survival, defining events as: ulcer progression, major amputation, or death. Patients were grouped based on whether they received specialty care from at least one of six disciplines: endocrinology, infectious disease, orthopedic surgery, plastic surgery, podiatry, and vascular surgery. Multivariate Cox proportional hazard models estimated the association between specialty care and event-free survival, adjusting for sociodemographic factors and comorbidities, and stratifying on ulcer severity. Results: Patients who received specialty care had longer event-free survival compared to those who did not (log-rank p<0.001 for all ulcer severity strata). After adjusting, receipt of specialty care, compared to never, remained associated with improved outcomes for all ulcer severities (early stage adjusted hazard ratio 0.34, 95% CI 0.33–0.35, p<0.001; osteomyelitis aHR 0.22, 95% CI 0.20–0.23, p<0.001; gangrene aHR 0.22, 95% CI 0.20–0.24, p<0.001). Conclusions: Specialty care was associated with longer event-free survivals for patients with diabetic foot ulcers. Increased, equitable access to specialty care might improve diabetic foot ulcer outcomes and disparities. [ABSTRACT FROM AUTHOR]

Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for T2D risk factors related to systemic and WAT glucose and fat metabolism. Regulation of the NLRP3 inflammasome was explored using LDL without/with the inflammasome's priming and activation controls (LPS and ATP). LDL induced IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and macrophages. Subjects with high-apoB had higher WAT IL-1β-secretion independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in high-apoB subjects only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, subjects with high-apoB have higher WAT IL-1β-secretion that may explain their risk for T2D and may be related to LDL-induced priming of the NLRP3 inflammasome. ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood—Full Text View—ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Several studies have analyzed the ice margin behavior of the Quelccaya Ice Cap (QIC), Earth's largest tropical ice cap, through the Holocene. However, continuous integration of new information to produce a more cohesive history of the QIC is necessary. Here, the radiocarbon dates of 33 rooted plant specimens collected in situ along the western ice margin between 2002 and 2018 reveal the timing of its past extent as it advanced during the mid‐Holocene. The most recent evaluation of collected specimens indicates that the QIC margin advanced ∼350 m down the Challpacocha Valley between 7.1 and 4.5 ka BP. Past studies of documented ice extent on the western side of the QIC based on a variety of techniques are compiled to create a more comprehensive history of the QIC's behavior throughout the Holocene. Records of documented ice extent, as well as other proxy records, indicate a climate transition ∼5–7 ka BP that created the proper environmental conditions for the expansion of the QIC. Evidence from nearby valleys indicates that the QIC behaved similarly to the documented ice extent in the Challpacocha Valley in response to Holocene climatic fluctuations. The ability to collect the plant specimens and recent analysis of satellite imagery reveals rapid retreat rates of the western outlet glaciers from 1985 to 2020, leaving the western margin of the QIC at its smallest extent since the mid‐Holocene. Plain Language Summary: The area around the Quelccaya Ice Cap (QIC) is unique as wetland plant samples have been found preserved in their growth positions, buried by past advancing ice, whereas the ice typically removes vegetation and soil in its advance down a valley. Using the 14C dates of these plants, we map a 350‐m advance of the ice margin between 7.1 and 4.5 ka BP. Combined with a variety of previous studies involving different methods and records from ice and lacustrine sediment cores, a larger picture of the QIC's behavior comes into view. A largely accepted global climate shift between ∼7 and 5 ka BP occurred in tandem with the QIC's advance. Although the QIC has fluctuated before, at no time has the western margin receded to the current extent since the mid‐Holocene. This is indicated by the exposure of the plants and current margin retreat rates calculated from satellite imagery (1985–2020). Key Points: Mid‐Holocene advance of the Quelccaya Ice Cap (QIC) is documented using 14C dating of in situ vegetation exposed during the recent retreatPlant ages of ∼4.5 to ∼7.1 ka BP provide evidence of a mid‐Holocene climate transition and the QIC ice‐margin expansionAnalysis of satellite imagery from 1985 to 2020 documents a recent rapid retreat (∼20 m/yr) of the QIC margin [ABSTRACT FROM AUTHOR]

Sex-specific differences exist in insulin secretion (ISec) and sensitivity (IS) in humans. However, current fasting indices used to estimate them, such as HOMA and QUICKI, are not sex-specific. We aimed to develop sex-specific models to improve the prediction of ISec and IS by fasting measures in adults with overweight/obesity. A post hoc analysis was conducted on baseline data of two clinical trials completed between 2010 and 2020 (37 men and 61 postmenopausal women, 45–73 years, BMI > 25 kg/m2, without chronic disease). Glucose-induced insulin or C-peptide secretions and IS were measured using gold-standard Botnia-clamps, which is a 1 h intravenous glucose tolerance test followed by a 3 h hyperinsulinemic–euglycemic clamp. Stepwise regression analysis using anthropometric and fasting plasma glucose, insulin, and lipoprotein-related measures was used to predict ISec and IS. First-phase, second-phase and total glucose-induced ISec were predicted by a combination of fasting plasma insulin and apoB without or with plasma glucose, triglyceride, and waist circumference in women (R2 = 0.58–0.69), and by plasma insulin and glucose without or with BMI and cholesterol in men (R2 = 0.41–0.83). Plasma C-peptide, alone in men or followed by glucose in women, predicted C-peptide secretion. IS was predicted by plasma insulin and waist circumference, followed by HDL-C in women (R2 = 0.57) or by glucose in men (R2 = 0.67). The sex-specific models agreed with the Botnia-clamp measurements of ISec and IS more than with HOMA or QUICKI. Sex-specific models incorporating anthropometric and lipoprotein-related parameters allowed better prediction of ISec and IS in subjects with overweight or obesity than current indices that rely on glucose and insulin alone. [ABSTRACT FROM AUTHOR]

Unique identification of optical devices is important for anti-counterfeiting. Physical unclonable functions (PUFs), which use random physical characteristics for authentication, are advantageous over existing optical solutions, such as holograms, due to the inherent asymmetry in their fabrication and reproduction complexity. However, whilst unique, PUFs are potentially vulnerable to replication and simulation. Here we introduce an additional benefit of a small modification to an established model of nanoparticle PUFs by using a second measurement parameter to verify their authenticity. A randomly deposited array of quantum dots is encapsulated in a transparent polymer, forming a tag. Photoluminescence is measured as a function of excitation power to assess uniqueness as well as the intrinsic nonlinear response of the quantum material. This captures a fingerprint, which is non-trivial to clone or simulate. To demonstrate this concept practically, we show that these tags can be read using an unmodified smartphone, with its built-in flash for excitation. This development over constellation-style optical PUFs paves the way for more secure, facile authentication of devices without requiring complex fabrication or characterisation techniques. [ABSTRACT FROM AUTHOR]

Background: Little is known about the content of communication in palliative care telehealth conversations in the dialysis population. Understanding the content and process of these conversations may lead to insights about how palliative care improves quality of life. Methods: We conducted a qualitative analysis of video recordings obtained during a pilot palliative teleconsultation program. We recruited patients receiving dialysis from five facilities affiliated with an academic medical center. Palliative care clinicians conducted teleconsultation using a wall-mounted screen with a camera mounted on a pole and positioned mid-screen in the line of sight to facilitate direct eye contact. Patients used an iPad that was attached to an IV pole positioned next to the dialysis chair. Conversations were coded using a preexisting framework of themes and content from the Serious Illness Conversation Guide (SICG) and revised Edmonton Symptom Assessment System—Renal. Results: We recruited 39 patients to undergo a telepalliative care consultation while receiving dialysis, 34 of whom completed the teleconsultation. Specialty palliative care clinicians (3 physicians and 1 nurse practitioner) conducted 35 visits with 34 patients. Median (interquartile range) duration of conversation was 42 (28–57) minutes. Most frequently discussed content included sources of strength (91%), critical abilities (88%), illness understanding (85%), fears and worries (85%), what family knows (85%), fatigue (77%), and pain (65%). Process features such as summarizing statements (85%) and making a recommendation (82%) were common, whereas connectional silence (56%), and emotion expression (21%) occurred less often. Conclusions: Unscripted palliative care conversations in outpatient dialysis units through telemedicine exhibited many domains recommended by the SICG, with less frequent discussion of symptoms. Emotion expression was uncommon for these conversations that occurred in an open setting. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized primarily by synovial hyperplasia and accumulation of several types of immune infiltrates that promote progressive destruction of the articular structure. Glucocorticoids are often prescribed to treat RA because of their strong anti-inflammatory and immunosuppressive effects. However, their application must be limited to the short-term due to a risk of adverse events. In the present study, we examined the potential combination of low-dose prednisone with gene delivery of an agent of promising and complementary effectiveness in RA, interleukin (IL)-27. IL-27 has been shown to have anti-inflammatory potential, while also acting as an effective bone-normalization agent in prior reports. The present report examined a version of IL-27 targeted at the C-terminus with a short 'peptide L' (pepL, LSLITRL) that binds the interleukin 6 receptor α (IL-6Rα) upregulated during inflammation. By focusing on this targeted form, IL-27pepL or 27pL, we examined whether the anti-inflammatory potential of prednisone (at a relatively low dose and short duration) could be further enhanced in the presence of 27pL as a therapy adjuvant. Our results indicate that 27pL represents a novel tool for use as an adjuvant with current therapeutics, such as prednisone, against inflammatory conditions. [ABSTRACT FROM AUTHOR]

Melanins are a class of biopolymers that are widespread in nature, with diverse origins, compositions, and functions, and their chemical and optoelectronic properties render them potentially useful for application in materials science for various biotechnological applications. For patients with alkaptonuria, the accumulation of homogentisic acid (HGA) in their bodies is associated with the concomitant deposition of pyomelanin, which is a pigment that contains significant amounts of polymerized HGA (polyHGA) in the bodily tissues of the patients. The polymerization of HGA under various different conditions in vitro is investigated using a selection of different analytical chemistry techniques to understand if there may be a correlation between the conditions and pigment deposition in vivo, and their potential for application as green/sustainable and components of electronic devices. [ABSTRACT FROM AUTHOR]

The diffusion of corporate social responsibility is investigated by employing a hybrid evolutionary game where a firm chooses between being either socially responsible, which implies devoting a fraction of its profit to social projects, or non-socially responsible. Consumers prize socially responsible companies by paying a higher reservation price for their products. The hybrid evolutionary framework is characterized by a quantity dynamics that describes the oligopolistic competition given firms' belief about the composition of the industry. At regular intervals of time, this belief is endogenously updated by a retrospective comparison on the profits obtained and on the basis of an evolutionary mechanism. Assuming that firms are Nash players, that is at each instant of time they produce the Nash equilibrium-in-belief quantity, the investigation of the model reveals that an industry homogeneously populated by socially responsible firms is a stable equilibrium when the fraction of profits earmarked for socially responsible activities is sufficiently limited. However, the extra marginal profits of a socially responsible firm are reduced when the number of competitors increases, impeding the diffusion of socially responsible companies. In particular, the trade-off between a higher net margin on sales obtained by socially responsible firms and a lower level of production that reduces the profit gap between a socially responsible firm and the rest of the market shows that an increased size of the industry favors mixed oligopolies. Moreover, imposing the hypothesis of neutrality of CSR activities, the model reveals that being socially responsible is an evolutionarily stable strategy for firms and is convenient for customers. Relaxing the hypothesis of Nash players by introducing boundedly rational firms that decide their level of production according to a partial adjustment toward the best reply, the robustness of these results is confirmed. [ABSTRACT FROM AUTHOR]

We propose an oligopoly model where players can choose between two kinds of behaviors, denoted as cooperative and aggressive, respectively. Each cooperative agent chooses the quantity to produce in order to maximize her own profit as well as the profits of other agents (at least partially), whereas an aggressive player decides the quantity to produce by maximizing his own profit while damaging (at least partially) competitors' profits. At each discrete time, players face a binary choice to select the kind of behavior to adopt, according to a proportional imitation rule, expressed by a replicator equation based on a comparison between accumulated profits. This means that the behavioral decisions are driven by an evolutionary process where fitness is measured in terms of current profits as well as a weighted sum of past gains. The model proposed is expressed by a nonlinear two-dimensional iterated map, whose asymptotic behavior describes the long-run population distribution of cooperative and aggressive agents. We show under which conditions one of the following long-run behaviors prevails: (i) all players choose the same strategy; (ii) both behaviors coexist according to a mixed stationary equilibrium; and (iii) a self-sustained (i.e. endogenous) oscillatory (periodic or chaotic) time pattern occurs. The influence of memory and that of the levels of cooperative/aggressive attitudes on the dynamics are analyzed as well. [ABSTRACT FROM AUTHOR]

In this paper, we analyze a bio-economic model of exploitation of renewable commercial resources. To take into account the typically continuous-time modeling of biological species and, instead, of the specialized harvesting activities, which by its nature cannot change continuously, the resulting dynamic system is of the hybrid type, i.e. continuous for biological variables and discrete for the economic ones. Through a discretization of the continuous variables, the problem is then reformulated by means of a three-dimensional map. Of this map, we study the dynamic properties to understand how economic parameters influence the long-run availability of resources. [ABSTRACT FROM AUTHOR]

Background: Patients receiving dialysis have unmet palliative care needs. Limited access to palliative care is a key barrier to its integration into routine dialysis care. Objective: To determine the feasibility and acceptability of telepalliative care in rural dialysis units. Methods: This was a single-arm pilot clinical trial. The target population was patients with kidney failure receiving outpatient dialysis in a rural U.S. state. Feasibility was measured by one-month completion rate. Acceptability was measured using an adapted telemedicine questionnaire. Results: We recruited 39 patients with mean age 71.2 years to undergo a telepalliative care consultation while receiving dialysis. Four specialty palliative care clinicians (three physicians and one nurse practitioner) conducted the visits. The recruitment rate was 40% (39/96), scheduling rate was 100% (39/39), and one-month completion rate was 77% (30/39). Thirty-six patient participants (14 women and 22 men) completed the baseline survey. Audiovisual aspects of the visit were rated highly. More than 80% reported the visit being at least as good as an in-person visit and 41% felt the teleconsult was better. Eighty-one percent of patients felt the appointment was relevant to them, 58% felt they learned new things about their condition, and 27% reported the appointment changed the way they think about dialysis. Discussion: Telepalliative care is acceptable to patients receiving dialysis and is a feasible approach to integrating palliative care in rural dialysis units. The study was registered with Clinicaltrials.gov (NCT03744117). [ABSTRACT FROM AUTHOR]

The paper studies tax evasion in an evolutionary setting. In addition to standard variables such as the fine individuals may have to pay if found guilty or the probability of being audited, agents' inclination to engage in tax evasion may also be affected by social interactions. Moreover, expected payoffs may include reputational costs or rewards awarded by society after an individual is audited. The paper shows how (i) social norms may play a very important role in defining the long‐run evolution of tax evasion and, consequently, that (ii) policymakers should consider reforms that would increase social awareness and information rather than more (financially and politically) expensive traditional auditing instruments; in addition, (iii) fiscal/auditing policies should be carefully tailored to the particular economic and social setting in place in a country. [ABSTRACT FROM AUTHOR]

Background/Objectives: The number of older adults with complex health needs is growing, and this population experiences disproportionate morbidity and mortality. Interventions led by community health workers (CHWs) can improve clinical outcomes in the general adult population with multimorbidity, but few studies have investigated CHW‐delivered interventions in older adults. Design: We systematically reviewed the impact of CHW interventions on health outcomes among older adults with complex health needs. We searched for English‐language articles from database inception through April 2020 using seven databases. PROSPERO protocol registration CRD42019118761. Setting: Any U.S. or international setting, including clinical and community‐based settings. Participants: Adults aged 60 years or older with complex health needs, defined in this review as multimorbidity, frailty, disability, or high‐utilization. Interventions: Interventions led by a CHW or similar role consistent with the American Public Health Association's definition of CHWs. Measurements: Pre‐defined health outcomes (chronic disease measures, general health measures, treatment adherence, quality of life, or functional measures) as well as qualitative findings. Results: Of 5671 unique records, nine studies met eligibility criteria, including four randomized controlled trials, three quasi‐experimental studies, and two qualitative studies. Target population and intervention characteristics were variable, and studies were generally of low‐to‐moderate methodological quality. Outcomes included mood, functional status and disability, social support, well‐being and quality of life, medication knowledge, and certain health conditions (e.g., falls, cognition). Results were mixed with several studies demonstrating significant effects on mood and function, including one high‐quality RCT, while others noted no significant intervention effects on outcomes. Conclusion: CHW‐led interventions may have benefit for older adults with complex health needs, but additional high‐quality studies are needed to definitively determine the effectiveness of CHW interventions in this population. Integration of CHWs into geriatric clinical settings may be a strategy to deliver evidence‐based interventions and improve clinical outcomes in complex older adults. See related editorial by Thompson et al. [ABSTRACT FROM AUTHOR]

In this paper, the location patterns of Multinational Enterprises are modeled by an evolutionary two-country model in which producing in a developed economy offers strong cost-reducing externalities of within-country spillovers and opting for a developing economy entails cheap labor but also extra operational costs due to the undersupply of public goods. The offshoring process, that is, manufacturing activity outsourced in the developing economy, increases the bargaining power of its workers and, with it, its labor cost. The investigation underlines that an increasing labor-productivity remuneration in the developing economy may spark a reshoring process that depends on the agglomeration and endowment drivers characterizing an industry. The reshoring process can be narrowed by a flexible labor remuneration scheme, with wages indexed to the domestic concentration of manufacturing activity. The presence of sub-optimal location patterns points out the existence of a trade-off between stability and efficiency, which underlines that policy measures designed to make a country a more efficient location are neither sufficient nor necessary for preventing offshoring or ensuring reshoring. [ABSTRACT FROM AUTHOR]

Composition of fatty acids (FAs) in soybean seed is important for the quality and uses of soybean oil. Using gas chromatography, we have measured soybean FAs profiles of 621 soybean accessions (maturity groups I through IV) grown in five different environments; Columbus, OH (2015), Wooster, OH (2014 and 2015), Plymouth, NC (2015), and Urbana, IL (2015). Using publicly available SoySNP50K genotypic data and the FA profiles from this study, a genome-wide association analysis was completed with a compressed mixed linear model to identify 43 genomic regions significantly associated with a fatty acid at a genome wide significance threshold of 5%. Among these regions, one and three novel genomic regions associated with palmitic acid and stearic acid, respectively, were identified across all five environments. Additionally, nine novel environment-specific FA-related genomic regions were discovered providing new insights into the genetics of soybean FAs. Previously reported FA-related loci, such as FATB1a, SACPD-C, and KASIII, were also confirmed in this study. Our results will be useful for future functional studies and marker-assisted breeding for soybean FAs. [ABSTRACT FROM AUTHOR]

Background: LDL‐cholesterol lowering variants that upregulate receptor uptake of LDL, such as in PCSK9 and HMGCR, are associated with diabetes via unclear mechanisms. Activation of the NLRP3 inflammasome/interleukin‐1 beta (IL‐1β) pathway promotes white adipose tissue (WAT) dysfunction and type 2 diabetes (T2D) and is regulated by LDL receptors (LDLR and CD36). We hypothesized that: (a) normocholesterolemic subjects with lower plasma PCSK9, identifying those with higher WAT surface‐expression of LDLR and CD36, have higher activation of WAT NLRP3 inflammasome and T2D risk factors, and; (b) LDL upregulate adipocyte NLRP3 inflammasome and inhibit adipocyte function. Methodology: Post hoc analysis was conducted in 27 overweight/ obese subjects with normal plasma LDL‐C and measures of disposition index (DI during Botnia clamps) and postprandial fat metabolism. WAT was assessed for surface‐expression of LDLR and CD36 (immunohistochemistry), protein expression (immunoblot), IL‐1β secretion (AlphaLISA), and function (3H‐triolein storage). Results: Compared to subjects with higher than median plasma PCSK9, subjects with lower PCSK9 had higher WAT surface‐expression of LDLR (+81%) and CD36 (+36%), WAT IL‐1β secretion (+284%), plasma IL‐1 receptor‐antagonist (+85%), and postprandial hypertriglyceridemia, and lower WAT pro‐IL‐1β protein (−66%), WAT function (−62%), and DI (−28%), without group‐differences in body composition, energy intake or expenditure. Adjusting for WAT LDLR or CD36 eliminated group‐differences in WAT function, DI, and postprandial hypertriglyceridemia. Native LDL inhibited Simpson‐Golabi Behmel‐syndrome (SGBS) adipocyte differentiation and function and increased inflammation. Conclusion: Normocholesterolemic subjects with lower plasma PCSK9 and higher WAT surface‐expression of LDLR and CD36 have higher WAT NLRP3 inflammasome activation and T2D risk factors. This may be due to LDL‐induced inhibition of adipocyte function. [ABSTRACT FROM AUTHOR]

Mesenchephalic and rhombencephalic neural crest cells generate the craniofacial skeleton, special sensory organs, and subsets of cranial sensory receptor neurons. They do so while preserving the anterior-posterior (A-P) identity of their neural tube origins. This organizational principle is paralleled by central nervous system circuits that receive and process information from facial structures whose A-P identity is in register with that in the brain. Prior to morphogenesis of the face and its circuits, however, neural crest cells act as "inductive ambassadors" from distinct regions of the neural tube to induce differentiation of target craniofacial domains and establish an initial interface between the brain and face. At every site of bilateral, non-axial secondary induction, neural crest constitutes all or some of the mesenchymal compartment for non-axial mesenchymal/epithelial (M/E) interactions. Thus, for epithelial domains in the craniofacial primordia, aortic arches, limbs, the spinal cord, and the forebrain (Fb), neural crest-derived mesenchymal cells establish local sources of inductive signaling molecules that drive morphogenesis and cellular differentiation. This common mechanism for building brains, faces, limbs, and hearts, A-P axis specified, neural crest-mediated M/E induction, coordinates differentiation of distal structures, peripheral neurons that provide their sensory or autonomic innervation in some cases, and central neural circuits that regulate their behavioral functions. The essential role of this neural crest-mediated mechanism identifies it as a prime target for pathogenesis in a broad range of neurodevelopmental disorders. Thus, the face and the brain "predict" one another, and this mutual developmental relationship provides a key target for disruption by developmental pathology. [ABSTRACT FROM AUTHOR]

Objective: Human conditions with upregulated receptor uptake of low-density lipoproteins (LDL) are associated with diabetes risk, the reasons for which remain unexplored. LDL induce metabolic dysfunction in murine adipocytes. Thus, it was hypothesized that white adipose tissue (WAT) surface expression of LDL receptor (LDLR) and/or CD36 is associated with WAT and systemic metabolic dysfunction. Whether WAT LDLR and CD36 expression is predicted by plasma lipoprotein-related parameters was also explored.Methods: This was a cross-sectional analysis of 31 nondiabetic adults (BMI > 25 kg/m2 ) assessed for WAT surface expression of LDLR and CD36 (immunohistochemistry), WAT function, WAT and systemic inflammation, postprandial fat metabolism, and insulin resistance (IR; hyperinsulinemic-euglycemic clamp).Results: Fasting WAT surface expression of LDLR and CD36 was negatively associated with WAT function (3 H-triglyceride storage, r = -0.45 and -0.66, respectively) and positively associated with plasma IL-1 receptor antagonist (r = 0.64 and 0.43, respectively). Their expression was suppressed 4 hours postprandially, and reduced LDLR was further associated with IR (M/Iclamp , r = 0.61 women, r = 0.80 men). Plasma apolipoprotein B (apoB)-to-PCSK9 ratio predicted WAT surface expression of LDLR and CD36, WAT dysfunction, WAT NLRP3 inflammasome priming and disrupted cholesterol-sensing genes, and systemic IR independent of sex and body composition.Conclusions: Higher fasting and lower postprandial WAT surface expression of LDLR and CD36 is associated with WAT dysfunction, systemic inflammation, and IR in adults with overweight/obesity, anomalies that are predicted by higher plasma apoB-to-PCSK9 ratio. [ABSTRACT FROM AUTHOR]

In this paper, we propose a unitary formulation for evolutionary oligopoly models with memory. In particular, we consider behavioral rules that are stationary at the Nash equilibria so that we can study the stability of the oligopolistic model with memory with generic strategies for determining quantities. Although the introduction of memory does not affect the local stability properties of equilibria, we show how the presence of memory impacts the global dynamics of the system and how the question about the role of memory does not always provide a clear answer in terms of model complexity. [ABSTRACT FROM AUTHOR]

Background: The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system has become a powerful tool for functional genomics in plants. The RNA-guided nuclease can be used to not only generate precise genomic mutations, but also to manipulate gene expression when present as a deactivated protein (dCas9). Results: In this study, we describe a vector toolkit for analyzing dCas9-mediated activation (CRISPRa) or inactivation (CRISPRi) of gene expression in maize protoplasts. An improved maize protoplast isolation and transfection method is presented, as well as a description of dCas9 vectors to enhance or repress maize gene expression. Conclusions: We anticipate that this maize protoplast toolkit will streamline the analysis of gRNA candidates and facilitate genetic studies of important trait genes in this transformation-recalcitrant plant. [ABSTRACT FROM AUTHOR]

Background: Vitamin A regulates patterning of the pharyngeal arches, cranial nerves, and hindbrain that are essential for feeding and swallowing. In the LgDel mouse model of 22q11.2 deletion syndrome (22q11DS), morphogenesis of multiple structures involved in feeding and swallowing are dysmorphic. We asked whether changes in maternal dietary Vitamin A intake can modify cranial nerve, hindbrain and pharyngeal arch artery development in the embryo as well as lung pathology that can be a sign of aspiration dysphagia in LgDel pups. Methods: Three defined amounts of vitamin A (4, 10, and 16 IU/g) were provided in the maternal diet. Cranial nerve, hindbrain and pharyngeal arch artery development was evaluated in embryos and inflammation in the lungs of pups to determine the impact of altering maternal diet on these phenotypes. Results: Reduced maternal vitamin A intake improved whereas increased intake exacerbated lung inflammation in LgDel pups. These changes were accompanied by increased incidence and/or severity of pharyngeal arch artery and cranial nerve V (CN V) abnormalities in LgDel embryos as well as altered expression of Cyp26b1 in the hindbrain. Conclusions: Our studies demonstrate that variations in maternal vitamin A intake can influence the incidence and severity of phenotypes in a mouse model 22q11.2 deletion syndrome. [ABSTRACT FROM AUTHOR]

There are currently multiple approaches to facilitate gene therapy via intramuscular gene delivery, such as electroporation, viral delivery, or direct DNA injection with or without polymeric carriers. Each of these methods has benefits, but each method also has shortcomings preventing it from being established as the ideal technique. A promising method, ultrasound-mediated gene delivery (or sonodelivery) is inexpensive, widely available, reusable, minimally invasive, and safe. Hurdles to utilizing sonodelivery include choosing from a large variety of conditions, which are often dependent on the equipment and/or research group, and moderate transfection efficiencies when compared to some other gene delivery methods. In this review, we provide a comprehensive look at the breadth of sonodelivery techniques for intramuscular gene delivery and suggest future directions for this continuously evolving field. [ABSTRACT FROM AUTHOR]

All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward—perinatal dysphagia—is often associated with several neurodevelopmental disorders that subsequently alter complex behaviors. Apparently, a broad range of neurodevelopmental pathologic mechanisms also target oropharyngeal and cranial nerve differentiation. These aberrant mechanisms, including altered patterning, progenitor specification, and neurite growth, prefigure dysphagia and may then compromise circuits for additional behavioral capacities. Thus, perinatal dysphagia may be an early indicator of disrupted genetic and developmental programs that compromise neural circuits and yield a broad range of behavioral deficits in neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

As the prevalence of persons with dementia increases, a larger, trained, and skilled healthcare workforce is needed. Attention has been given to models of person-centered care as a standard for dementia care. One promising role to deliver person-centered care is the care coordinator assistant. An inquiry about care coordinator assistant's job satisfaction is reasonable to consider for retention and quality improvement purposes. We evaluated care coordinator assistants' job satisfaction quantitatively and qualitatively. This study was part of a Centers for Medicare & Medicaid Services Health Care Innovation Award to the Indiana University School of Medicine. Sixteen care coordinator assistants, predominately female, African American or Caucasian, college graduates with a mean age of 43.1 years participated. Care coordinator assistants wrote quarterly case reports to share stories, lessons learned, and/or the impact of their job and completed the revised Job Satisfaction Inventory and Job in General scales during the second year of the Centers for Medicare & Medicaid Services award. For the Job Descriptive Index subscales promotion, supervision, and coworkers and Job in General, care coordinator assistants scored similar to normative means. Care coordinator assistants reported significantly higher satisfaction on the work subscale and significantly lower satisfaction on the pay subscale compared to normative data. Care coordinator assistants completed 119 quarterly case reports. Job satisfaction and teamwork were recurring themes in case reports, referenced in 47.1% and 60.5% of case reports, respectively. To address the demands of increasing dementia diagnoses, care coordinator assistants can constitute a compassionate, competent, and satisfied workforce. Training care coordinator assistants to work together in a team to address the needs of persons with dementia and caregivers provides a viable model of workforce development necessary to meet the growing demands of this population. [ABSTRACT FROM AUTHOR]

Disrupted development of oropharyngeal structures as well as cranial nerve and brainstem circuits may lead to feeding and swallowing difficulties in children with 22q11. 2 deletion syndrome (22q11DS). We previously demonstrated aspiration-based dysphagia during early postnatal life in the LgDel mouse model of 22q11DS along with disrupted oropharyngeal morphogenesis and divergent differentiation and function of cranial motor and sensory nerves. We now ask whether feeding and swallowing deficits persist in adult LgDel mice using methods analogous to those used in human patients to evaluate feeding and swallowing dysfunction. Compared to wild-type mice, videofluoroscopic swallow study revealed that LgDel mice have altered feeding and swallowing behaviors, including slower lick rates, longer inter-lick intervals, and longer pharyngeal transit times with liquid consistency. Transoral endoscopic assessment identified minor structural anomalies of the palate and larynx in one-third of the LgDel mice examined. Video surveillance of feeding-related behaviors showed that LgDel mice eat and drink more frequently. Furthermore, LgDel animals engage in another oromotor behavior, grooming, more frequently, implying that divergent craniofacial and cranial nerve structure and function result in altered oromotor coordination. Finally, LgDel mice have significantly increased lung inflammation, a potential sign of aspiration-based dysphagia, consistent with results from our previous studies of early postnatal animals showing aspiration-related lung inflammation. Thus, oromotor dysfunction, feeding, and swallowing difficulties and their consequences persist in the LgDel 22q11DS mouse model. Apparently, postnatal growth and/or neural plasticity does not fully resolve deficits due to anomalous hindbrain, craniofacial, and cranial nerve development that prefigure perinatal dysphagia in 22q11DS. This new recognition of persistent challenges with feeding and swallowing may provide opportunities for improved therapeutic intervention for adolescents and adults with 22q11DS, as well as others with a history of perinatal feeding and swallowing disorders. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Contemporary literature on Symeon the New Theologian often characterizing as a mystic focusing on the mystical theology and visions of fire and light. Topics include describing three different aspects of deification such as the incarnation, the sacraments, and the Church; and opening up participation in the fullness of divine life inaccessible to humans before Christ.