Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults, a randomized, parallel arm, double-blind, placebo-controlled, pilot study.

Objectives: Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to determine tolerability and safety of KE ingestion in older adults. Design: Randomized, placebo-controlled, double-blinded, parallel-arm trial, with a 12-week intervention period ( NCT05585762 ). Setting: General community, Northern California, USA. Participants: Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n=30) were randomized and n=23 (M= 14, F=9) completed the protocol. Intervention: Participants were randomly allocated to consume either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil. Measurements: Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events. Results: There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n =2 (14.3% [90% CI = 2.6 - 38.5]); PLA n=1 (7.1% [90% CI = 0.4 - 29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 - 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group. Conclusions: This KE was safe and well-tolerated in healthy older adults. These results provide a foundation for use of KEs in aging research. Highlights: Ketones esters induce ketosis without dietary changes and may target aging biologyStudies of ketone esters were limited in duration and focused on younger adultsWe found ketone esters were safe and tolerable for 12 weeks in healthy older adults.

A randomized open-label, observational study of the novel ketone ester, bis octanoyl (R)-1,3-butanediol, and its acute effect on ß-hydroxybutyrate and glucose concentrations in healthy older adults.

Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel ketone ester (KE) ingredient which increases blood beta-hydroxybutyrate (BHB) concentrations rapidly after ingestion. KE is hypothesized to have beneficial metabolic effects on health and performance, especially in older adults. Whilst many studies have investigated the ketogenic effect of KE in young adults, they have not been studied in an exclusively older adult population, for whom age-related differences in body composition and metabolism may alter the effects. This randomized, observational, open-label study in healthy older adults (n = 30, 50% male, age = 76.5 years, BMI = 25.2 kg/m2) aimed to elucidate acute tolerance, blood BHB and blood glucose concentrations for 4 hours following consumption of either 12.5 or 25 g of BO-BD formulated firstly as a ready-to-drink beverage (n = 30), then as a re-constituted powder (n = 21), taken with a standard meal. Both serving sizes and formulations of BO-BD were well tolerated, and increased blood BHB, inducing nutritional ketosis (≥ 0.5mM) that lasted until the end of the study. Ketosis was dose responsive; peak BHB concentration (Cmax) and incremental area under the curve (iAUC) were significantly greater with 25 g compared to 12.5 g of BO-BD in both formulations. There were no significant differences in Cmax or iAUC between formulations. Blood glucose increased in all conditions following the meal; there were no consistent significant differences in glucose response between conditions. These results demonstrate that both powder and beverage formulations of the novel KE, BO-BD, induce ketosis in healthy older adults, facilitating future research on functional effects of this ingredient in aging.

Peripheral HMGB1 is linked to O3 pathology of disease-associated astrocytes and amyloid.

INTRODUCTION: Ozone (O3) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung-brain axis is implicated in O3-associated glial and amyloid pathobiology; however, the role of disease-associated astrocytes (DAAs) in this process remains unknown. METHODS: The O3-induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics. Hmgb1fl/fl LysM-Cre+ mice were used to assess the role of peripheral myeloid cell high mobility group box 1 (HMGB1). RESULTS: O3 increased astrocyte and plaque numbers, impeded the astrocyte proteomic response to plaque deposition, augmented the DAA transcriptional fingerprint, increased astrocyte-microglia contact, and reduced bronchoalveolar lavage immune cell HMGB1 expression in 5xFAD mice. O3-exposed Hmgb1fl/fl LysM-Cre+ mice exhibited dysregulated DAA mRNA markers. DISCUSSION: Astrocytes and peripheral myeloid cells are critical lung-brain axis interactors. HMGB1 loss in peripheral myeloid cells regulates the O3-induced DAA phenotype. These findings demonstrate a mechanism and potential intervention target for air pollution-induced AD pathobiology. HIGHLIGHTS: Astrocytes are part of the lung-brain axis, regulating how air pollution affects plaque pathology. Ozone (O3) astrocyte effects are associated with increased plaques and modified by plaque localization. O3 uniquely disrupts the astrocyte transcriptomic and proteomic disease-associated astrocyte (DAA) phenotype in plaque associated astrocytes (PAA). O3 changes the PAA cell contact with microglia and cell-cell communication gene expression. Peripheral myeloid cell high mobility group box 1 regulates O3-induced transcriptomic changes in the DAA phenotype.

Stabilizing effect of an elbow orthosis with an adjustable hinge axis after lateral collateral ligament injury: A biomechanical study.

Background: Current commercial elbow braces have a straight hinge that does not account for the native carrying angle of the elbow. The objective of this study was to determine the effectiveness of a custom-designed hinged elbow orthosis (HEO) with variable valgus angulations in stabilizing a lateral collateral ligament (LCL) deficient elbow. Methods: Eight cadaveric upper extremities were mounted in an elbow motion simulator in the abducted varus gravity-loaded position. The specimens were examined before and after simulated LCL injury and then with the addition of the custom-designed HEO with 0°, 10°, and 20° of valgus angulation. Kinematic data were recorded using an electromagnetic tracking system. Results: The LCL injured state with or without the brace resulted in significant increases in varus angulation of the elbow compared to the intact state in both pronation and supination (P < 0.05). There were no significant differences in varus-valgus angulation or ulnohumeral rotation between any of the brace angles and the LCL injured state with the forearm pronated and supinated. Discussion: The custom-designed HEO did not provide any additional stability to the LCL injured elbow. The varus arm position should be avoided during the rehabilitation of an LCL injured elbow even when an HEO is used.

Blood flow restriction training does not negatively alter the mechanical strength or histomorphology of uninjured equine superficial digital flexor tendons.

BACKGROUND: Low load exercise training with blood flow restriction (BFR) has become increasingly used by human physical therapists to prescribe controlled exercise following orthopaedic injury; its effects on the equine superficial digital flexor tendon (SDFT), however, are unknown. OBJECTIVE: To investigate outcomes of pressure specific BFR walking exercise on uninjured equine SDFT biomechanics and histomorphology. STUDY DESIGN: Controlled in vivo experiment. METHODS: Four forelimbs of four horses were exposed to 40 BFR-walk sessions (10-min interval walking) on a treadmill over a 56-day study period with their contralateral forelimbs serving as untreated controls. Similarly, four forelimbs of four control horses were exposed to 40 sham cuff walk sessions. On study Day 56, all horses (n = 8) were humanely euthanised and forelimb SDFTs underwent non-destructive biomechanical testing and corresponding histomorphological analysis. Significance in biomechanical parameters between treatment groups was analysed using a mixed-effects ANOVA with Tukey's post-hoc tests. RESULTS: Statistically significant differences in SDFT stiffness for both first (p = 0.02) and last cycles (p = 0.03) were appreciated within the BFR treated group only, with BFR exposed forelimbs being significantly stiffer than the contralateral unexposed forelimbs. When normalised to cross-sectional area, no significant differences were appreciated among treatment groups in elastic modulus for the first (p = 0.5) or last cycles (p = 0.4). No histological differences were appreciated among treatment groups according to Bonar, Movin, or musculotendinous junction evaluation criteria. MAIN LIMITATIONS: Short-term comparisons were performed in a small sample population without correlation to performance outcome measures. Optimal occlusion percentages and walk protocols remain unknown. CONCLUSIONS: This study demonstrated no negative impact of BFR on mechanical strength of the equine SDFT; however, evidence suggests that BFR results in increased tendon stiffness based on biomechanical testing and subsequent calculations. No consistent detrimental histomorphological changes were seen.

CONTEXTO: Exercício de baixa carga com restrição do fluxo sanguíneo (RFS) tem sido cada vez mais utilizado por fisioterapeutas humanos para tratar lesões ortopédicas. Porém, seus efeitos no tendão flexor digital superficial (TFDS) de equinos não é conhecida. OBJETIVOS: O objetivo deste estudo foi investigar o efeito de específicas pressões com RFS durante o passo em cavalos sem lesão no TFDS, por meio de histologia e análise biomecânica. DELINEAMENTO DO ESTUDO: Estudo controlado. MÉTODOS: Quatro membros torácicos de quatro cavalos foram expostos a 40 sessões de RFS durante o passo (10 minutos de caminhada intervalada), ao longo de 56 dias. O membro contralateral foi utilizado como controle. Da mesma forma, quatro membros de quatro cavalos controle foram expostos a 40 sessões simuladas de caminhada com torniquete. No dia 56, todos os cavalos (n = 8) foram eutanasiados, e os TFDS foram submetidos a testes biomecânicos não destrutivos e análise histológica. A significância dos parâmetros biomecânicos entre tratamentos foi analisada utilizando ANOVA de efeitos mistos, seguida pelo teste de Tukey. RESULTADOS: A rigidez do TFDS foi estatisticamente diferente nos primeiros (p = 0.02) e últimos (p = 0.03) ciclos no grupo submetido à RFS, sendo os membros tratados significativamente mais rígidos do que os membros contralaterais não expostos ao tratamento. Quando normalizado para a área transversal, não foi observada diferença significativa entre os grupos de tratamento no módulo de elasticidade para os primeiros (p = 0.5) e últimos (p = 0.4) ciclos. Não foram identificadas diferenças histológicas nos diferentes tipos de tratamento, de acordo com os critérios de avaliação Bonar, Movin e de junção musculo­tendínea. PRINCIPAIS LIMITAÇÕES: Comparações de curto prazo foram realizadas em uma amostra pequena da população, sem correlação com medidas de resultados de desempenho. As porcentagens ideais de oclusão e os protocolos de caminhada permanecem desconhecidos. CONCLUSÕES: Este estudo não demonstrou impacto negativo do RFS na resistência mecânica do TFDS equino; no entanto, as evidências sugerem que a RFS resulta em aumento da rigidez do tendão com base em testes biomecânicos e cálculos subsequentes. Nenhuma alteração histológica prejudicial consistente foi observada.

Passive high explosive neutron inspection (PHENIX): a new method to confirm the presence or absence of high explosives for nuclear treaty verification.

Advanced instruments and methods need to be developed now to create a technical basis to support the negotiation of future nuclear arms control treaties. One new capability that is anticipated is the ability to confirm either the declared presence or declared absence of high explosive (HE) material in the presence of special nuclear material (SNM). Towards this goal, Passive HE Neutron Inspection (PHENIX) has been developed and demonstrated as a method for confirming the presence or absence of HE in the presence of plutonium. The method exploits the inherent presence of neutrons associated with the decay of plutonium as an internal probe source for performing prompt gamma-ray neutron activation analysis (PGNAA), searching for the presence of HE as revealed by the emission of characteristic gamma rays following neutron absorption in hydrogen and nitrogen which are building blocks of present-day, military-grade HE. Tests using stoichiometrically-correct hemishells of mock HE with plutonium show that a system can be expected to positively confirm the presence or absence of these signatures, supporting determination of HE presence or absence with Pu, in a few hours. To protect other potentially sensitive gamma-ray signatures from a treaty accountable item, an analog information barrier has been conceptualized and tested which physically prevents the collection of gamma-ray spectral data outside of user selected energy windows strategically chosen to view only narrow spectral regions corresponding to the hydrogen (2223.2 keV) and nitrogen (9807.2 keV, 10,318.2 keV, and 10,829.2 keV) PGNAA signatures.

Pragmatic Approach to In Situ Simulation to Identify Latent Safety Threats Before Moving to a Newly Built ICU.

OBJECTIVES: Transitions to new care environments may have unexpected consequences that threaten patient safety. We undertook a quality improvement project using in situ simulation to learn the new patient care environment and expose latent safety threats before transitioning patients to a newly built adult ICU. DESIGN: Descriptive review of a patient safety initiative. SETTING: A newly built 24-bed neurocritical care unit at a tertiary care academic medical center. SUBJECTS: Care providers working in neurocritical care unit. INTERVENTIONS: We implemented a pragmatic three-stage in situ simulation program to learn a new patient care environment, transitioning patients from an open bay unit to a newly built private room-based ICU. The project tested the safety and efficiency of new workflows created by new patient- and family-centric features of the unit. We used standardized patients and high-fidelity mannequins to simulate patient scenarios, with "test" patients created through all electronic databases. Relevant personnel from clinical and nonclinical services participated in simulations and/or observed scenarios. We held a debriefing after each stage and scenario to identify safety threats and other concerns. Additional feedback was obtained via a written survey sent to all participants. We prospectively surveyed for missed latent safety threats for 2 years following the simulation and fixed issues as they arose. MEASUREMENTS AND MAIN RESULTS: We identified and addressed 70 latent safety threats, including issues concerning physical environment, infection prevention, patient workflow, and informatics before the move into the new unit. We also developed an orientation manual that highlighted new physical and functional features of the ICU and best practices gleaned from the simulations. All participants agreed or strongly agreed that simulations were beneficial. Two-year follow-up revealed only two missed latent safety threats. CONCLUSIONS: In situ simulation effectively identifies latent safety threats surrounding the transition to new ICUs and should be considered before moving into new units.

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.

Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. Here, we define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. While islets from the majority of donors exhibited the expected relative response magnitudes, with glucose being highest, amino acid moderate, and fatty acid small, 9% of islets stimulated with amino acid and 8% of islets stimulated with fatty acids had larger responses compared with high glucose. We leveraged this insulin response heterogeneity and used transcriptomics and proteomics to identify molecular correlates of specific nutrient responsiveness, as well as those proteins and mRNAs altered in type 2 diabetes. We also examine nutrient-responsiveness in stem cell-derived islet clusters and observe that they have dysregulated fuel sensitivity, which is a hallmark of functionally immature cells. Our study now represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people's islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition. ONE-SENTENCE SUMMARY: Deep phenotyping and multi-omics reveal individualized nutrient-specific insulin secretion propensity.

Confronting the Nursing Profession's Workforce Challenges: Embracing Iceberg Demographics.

U.S. Supreme Court rulings on reproductive rights and affirmative action inadvertently present the nursing profession with a propitious opportunity to capitalize on the nation's rich mosaic of iceberg demographic identities-inherited and acquired traits that may not be visibly apparent-to address imminent challenges such as worker shortages and other perplexities within the workplace milieu.

Web-based multi-omics integration using the Analyst software suite.

The growing number of multi-omics studies demands clear conceptual workflows coupled with easy-to-use software tools to facilitate data analysis and interpretation. This protocol covers three key components involved in multi-omics analysis, including single-omics data analysis, knowledge-driven integration using biological networks and data-driven integration through joint dimensionality reduction. Using the dataset from a recent multi-omics study of human pancreatic islet tissue and plasma samples, the first section introduces how to perform transcriptomics/proteomics data analysis using ExpressAnalyst and lipidomics data analysis using MetaboAnalyst. On the basis of significant features detected in these workflows, the second section demonstrates how to perform knowledge-driven integration using OmicsNet. The last section illustrates how to perform data-driven integration from the normalized omics data and metadata using OmicsAnalyst. The complete protocol can be executed in ~2 h. Compared with other available options for multi-omics integration, the Analyst software suite described in this protocol enables researchers to perform a wide range of omics data analysis tasks via a user-friendly web interface.

Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet.

BACKGROUND: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult. RESULTS: Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPß for methylated motifs and the preference of c-Myc for unmethylated E-box motifs. CONCLUSIONS: Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications.

Photobiomodulation Therapy Plus Usual Care Is Better than Usual Care Alone for Plantar Fasciitis: A Randomized Controlled Trial.

Background: Plantar fasciitis (PF) results in pain-related disability and excessive healthcare costs. Photobiomodulation therapy (PBMT) has shown promise for decreasing both pain and disability related to PF. Purpose: The purpose was to assess the clinical impact of PBMT on pain and function in people with PF. Study Design: Prospective, randomized controlled clinical trial. Methods: A convenience sample of adults with PF were randomly assigned to one of three groups: (1) usual care, (2) usual care plus nine doses of PBMT with 25W output power over three weeks, or (3) usual care plus nine doses of PBMT with 10W output power over three weeks. Both 10W and 25W PBMT participants received the same total dose (10J/cm2) by utilizing a simple area equation. Pain (with Defense and Veterans Pain Rating Scale) and function (by Foot and Ankle Ability Measure) were measured at baseline, weeks 3, and 6 for all groups, and at 13 and 26 weeks for PBMT groups. Results: PBMT groups experienced a reduction in pain over the first three weeks (from an average of 4.5 to 2.8) after which their pain levels remained mostly constant, while the UC group experienced a smaller reduction in pain (from an average of 4 to 3.8). The effects on pain were not different between PBMT groups. PBMT in both treatment groups also improved function more than the UC group, again with the improvement occurring within the first three weeks. Conclusions: Pain and function improved during the three weeks of PBMT plus UC and remained stable over the following three weeks. Improvements sustained through six months in the PBMT plus UC groups. Level of Evidence: Level II- RCT or Prospective Comparative Study.

CLINICAL AND HISTOPATHOLOGIC OCULAR FINDINGS IN AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS).

Cownose rays (Rhinoptera bonasus) are susceptible to ocular disease with their prominent globes, but despite being popular animals housed in aquaria, there is little published information about their normal ocular anatomy and common pathologic ocular findings. A total of 63 live cownose rays (CNR) from three unrelated, separately housed groups had ocular examinations, and 5 adult rays were selected for ocular ultrasound. All examinations were performed out of the water, and most without anesthesia. Clinical findings were described, categorized, and scored by severity. Sixty-two of 63 rays (123 eyes) had clinical abnormalities, including 110 eyes with corneal pathology (mild = 76, moderate/severe = 34) and 74 eyes with intraocular pathology (mild = 44, moderate/severe = 30). Grey-to-white corneal opacities were the most common pathology (n = 58 rays/100 eyes) followed by cataracts (n = 41 rays/58 eyes), then persistent (or dysplastic) pupillary membranes (n = 14 rays/15 eyes). Most pathologic findings appeared inactive, but one aquarium had several CNR with active ocular pathology. There was a significant association between the diagnosis of moderate/severe corneal and intraocular pathology with age (P = 0.008 and P = 0.014, respectively) and weight (P = 0.001 and P = 0.039, respectively), as well as moderate/severe corneal pathology and group sampled (P = 0.03). There were no other significant variables identified. Additionally, histopathology of 14 eyes (11 rays) from two different facilities were examined, with keratitis (n = 8) and uveitis (n = 2) as the most common lesions. This study shows a high prevalence of pathologic ocular findings in cownose ray eyes with heavier adults more likely to be affected than lighter juveniles. Comprehensive ocular evaluation is important in this species and serial ocular exams and future studies should be pursued to monitor ocular disease progression and better understand possible etiologies.

INTRAOCULAR PRESSURES OF AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS) WITH NORMAL AND ABNORMAL OPHTHALMIC EXAMS.

Cownose rays (Rhinoptera bonasus) are common elasmobranchs in zoos and aquaria; however, there is a lack of published information regarding ocular findings in this species. Intraocular pressure (IOP) was measured in a total of 52 cownose rays (Rhinoptera bonasus) from two unrelated aquaria (n = 22 from A1, n = 30 from A2) using a TonoVet rebound tonometer on two settings (dog = D, and unidentified species = P) as part of a full ophthalmologic examination. Adult (n = 38) and juvenile (n = 14) rays were sampled out of water briefly in sternal recumbency. Intraocular pressure (mean ± SD [range]) in the D setting (9.10 ± 2.57 [4-18] mmHg) was higher than the P setting (5.21 ± 2.32 [0-12] mmHg) (P<0.001). Statistical analysis revealed no difference in IOP between right and left eyes, and no correlation between body weight and IOP. No differences in IOP between sex, age group, and location were identified in either setting. However, a significant difference was observed between levels of severity of corneal disease in IOP D setting (P=0.006) and P setting (P=0.024), and levels of severity of intraocular disease in IOP D setting (P=0.034) only. This study provides baseline IOP values using rebound tonometry in aquarium-housed cownose rays with apparent corneal and intraocular lesions and reveals that the D setting may be more sensitive in identifying IOP changes in eyes with intraocular disease.

Using natural language processing to increase prediction and reduce subgroup differences in personnel selection decisions.

The purpose of this research is to demonstrate how using natural language processing (NLP) on narrative application data can improve prediction and reduce racial subgroup differences in scores used for selection decisions compared to mental ability test scores and numeric application data. We posit there is uncaptured and job-related constructs that can be gleaned from applicant text data using NLP. We test our hypotheses in an operational context across four samples (total N = 1,828) to predict selection into Officer Training School in the U.S. Air Force. Boards of three senior officers make selection decisions using a highly structured rating process based on mental ability tests, numeric application information (e.g., number of past jobs, college grades), and narrative application information (e.g., past job duties, achievements, interests, statements of objectives). Results showed that NLP scores of the narrative application generally (a) predict Board scores when combined with test scores and numeric application information at a level of correlation equivalent to the correlation between human raters (.60), (b) add incremental prediction of Board scores beyond mental ability tests and numeric application information, and (c) reduce subgroup differences between racial minorities and nonracial minorities in Board scores compared to mental ability tests and numeric application information. Moreover, NLP scores predict (a) job (training) performance, (b) job (training) performance beyond mental ability tests and numeric application information, and (c) even job (training) performance beyond Board scores. Scoring of narrative application data using NLP shows promise in addressing the validity-adverse impact dilemma in selection. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The effect of acute and 14-day exogenous ketone supplementation on glycemic control in adults with type 2 diabetes: two randomized controlled trials.

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.

White Americans' blame attributions and empathy towards Black victims of police violence: How pejorative stereotypes 'engulf the field'.

We examined the dynamics of minority-directed police violence by considering how our White participants' empathy for Black victims may be influenced by critical intragroup differences related to racial stereotyping. Although the role of stereotyping in reactions to Black Americans accused of crime is well-established, we explore the influence of pejorative Black stereotypes on reactions to Black victims of police violence. Specifically, we investigated the roles of individual differences in the endorsement of the Black criminal stereotype among White observers and manipulated the crime-unrelated stereotypicality (i.e. stereotypical, counterstereotypical) of Black victims of police violence. White US MTurk participants read about a White policeman shooting a Black man (Study 1, n = 140) or sexually assaulting a Black woman (Study 2, n = 166). Across both studies, strong stereotype endorsers reported relatively low empathy for stereotypical victims, mediated by greater blame towards those victims. This finding demonstrates the relevance of heretofore untested motivated reasoning processes in the outgroup empathy deficits literature. Weak stereotype endorsers showed relatively high empathy and low victim blame regardless of Black victim stereotypicality, indicating limited sensitivity to outgroup member suffering is not inevitable. We consider the practical implications of the findings for policing and for citizenship education.

Stemless reverse humeral component neck-shaft angle has an influence on initial fixation.

BACKGROUND: Stemless anatomic humeral components are commonly used and are an accepted alternative to traditional stemmed implants in patients with good bone quality. Presently, little literature exists on the design and implantation parameters that influence primary time-zero fixation of stemless reverse humeral implants. Accordingly, this finite element analysis study assessed the surgical implantation variable of neck-shaft angle, and its effect on the primary time-zero fixation of reversed stemless humeral implants. METHODS: Eight computed tomography-derived humeral finite element models were used to examine a generic stemless humeral implant at varying neck-shaft angles of 130°, 135°, 140°, 145°, and 150°. Four loading scenarios (30° shoulder abduction with neutral forearm rotation, 30° shoulder abduction with forearm supination, a head-height lifting motion, and a single-handed steering motion) were employed. Implantation inclinations were compared based on the maximum bone-implant interface distraction detected after loading. RESULTS: The implant-bone distraction was greatest in the 130° neck-shaft angle implantation cases. All implant loading scenarios elicited significantly lower micromotion magnitudes when neck-shaft angle was increased (P = .0001). With every 5° increase in neck-shaft angle, there was an average 17% reduction in bone-implant distraction. CONCLUSIONS: The neck-shaft angle of implantation for a stemless reverse humeral component is a modifiable parameter that appears to influence time-zero implant stability. Lower, more varus, neck-shaft angles increase bone-implant distractions with simulated activities of daily living. It is therefore suggested that humeral head osteotomies at a higher neck-shaft angle may be beneficial to maximize stemless humeral component stability.