The OPAQUE1/DISCORDIA2 myosin XI is required for phragmoplast guidance during asymmetric cell division in maize.

Formative asymmetric divisions produce cells with different fates and are critical for development. We show the maize (Zea mays) myosin XI protein, OPAQUE1 (O1), is necessary for asymmetric divisions during maize stomatal development. We analyzed stomatal precursor cells before and during asymmetric division to determine why o1 mutants have abnormal division planes. Cell polarization and nuclear positioning occur normally in the o1 mutant, and the future site of division is correctly specified. The defect in o1 becomes apparent during late cytokinesis, when the phragmoplast forms the nascent cell plate. Initial phragmoplast guidance in o1 is normal; however, as phragmoplast expansion continues o1 phragmoplasts become misguided. To understand how O1 contributes to phragmoplast guidance, we identified O1-interacting proteins. Maize kinesins related to the Arabidopsis thaliana division site markers PHRAGMOPLAST ORIENTING KINESINs (POKs), which are also required for correct phragmoplast guidance, physically interact with O1. We propose that different myosins are important at multiple steps of phragmoplast expansion, and the O1 actin motor and POK-like microtubule motors work together to ensure correct late-stage phragmoplast guidance.

Early activation of cellular stress and death pathways caused by cytoplasmic TDP-43 in the rNLS8 mouse model of ALS and FTD.

TAR DNA binding protein 43 (TDP-43) pathology is a key feature of over 95% of amyotrophic lateral sclerosis (ALS) and nearly half of frontotemporal dementia (FTD) cases. The pathogenic mechanisms of TDP-43 dysfunction are poorly understood, however, activation of cell stress pathways may contribute to pathogenesis. We, therefore, sought to identify which cell stress components are critical for driving disease onset and neurodegeneration in ALS and FTD. We studied the rNLS8 transgenic mouse model, which expresses human TDP-43 with a genetically-ablated nuclear localisation sequence within neurons of the brain and spinal cord resulting in cytoplasmic TDP-43 pathology and progressive motor dysfunction. Amongst numerous cell stress-related biological pathways profiled using qPCR arrays, several critical integrated stress response (ISR) effectors, including CCAAT/enhancer-binding homologous protein (Chop/Ddit3) and activating transcription factor 4 (Atf4), were upregulated in the cortex of rNLS8 mice prior to disease onset. This was accompanied by early up-regulation of anti-apoptotic gene Bcl2 and diverse pro-apoptotic genes including BH3-interacting domain death agonist (Bid). However, pro-apoptotic signalling predominated after onset of motor phenotypes. Notably, pro-apoptotic cleaved caspase-3 protein was elevated in the cortex of rNLS8 mice at later disease stages, suggesting that downstream activation of apoptosis drives neurodegeneration following failure of early protective responses. Unexpectedly, suppression of Chop in the brain and spinal cord using antisense oligonucleotide-mediated silencing had no effect on overall TDP-43 pathology or disease phenotypes in rNLS8 mice. Cytoplasmic TDP-43 accumulation therefore causes very early activation of ISR and both anti- and pro-apoptotic signalling that switches to predominant pro-apoptotic activation later in disease. These findings suggest that precise temporal modulation of cell stress and death pathways may be beneficial to protect against neurodegeneration in ALS and FTD.

Microrheology reveals microscale viscosity gradients in planktonic systems.

Microbial activity in planktonic systems creates a dynamic and heterogeneous microscale seascape that harbors a diverse community of microorganisms and ecological interactions of global significance. In recent decades great effort has been put into understanding this complex system, particularly focusing on the role of chemical patchiness, while overlooking a physical parameter that governs microbial life and is affected by biological activity: viscosity. Here we reveal spatial heterogeneity of viscosity in planktonic systems by using microrheological techniques that allow measurement of viscosity at length scales relevant to microorganisms. We show the viscous nature and the spatial extent of the phycosphere, the region surrounding phytoplankton. In ∼45% of the phytoplankton cells analyzed we detected increases in viscosity that extended up to 30 µm away from the cell with up to 40 times the viscosity of seawater. We also show how these gradients of viscosity can be amplified around a lysing phytoplankton cell as its viscous contents leak away. Finally, we report conservative estimates of viscosity inside marine aggregates, hotspots of microbial activity, more than an order of magnitude higher than in seawater. Since the diffusivities of dissolved molecules, particles, and microorganisms are inversely related to viscosity, microheterogeneity in viscosity alters the microscale distribution of microorganisms and their resources, with pervasive implications for the functioning of the planktonic ecosystem. Increasing viscosities impacts ecological interactions and processes, such as nutrient uptake, chemotaxis, and particle encounter, that occur at the microscale but influence carbon and nutrient cycles at a global scale.

Fully angularly resolved 3D microrheology with optical tweezers.

Microrheology with optical tweezers (MOT) is an all-optical technique that allows the user to investigate a materials' viscoelastic properties at microscopic scales, and is particularly useful for those materials that feature complex microstructures, such as biological samples. MOT is increasingly being employed alongside 3D imaging systems and particle tracking methods to generate maps showing not only how properties may vary between different points in a sample but also how at a single point the viscoelastic properties may vary with direction. However, due to the diffraction limited shape of focussed beams, optical traps are inherently anisotropic in 3D. This can result in a significant overestimation of the fluids' viscosity in certain directions. As such, the rheological properties can only be accurately probed along directions parallel or perpendicular to the axis of trap beam propagation. In this work, a new analytical method is demonstrated to overcome this potential artefact. This is achieved by performing principal component analysis on 3D MOT data to characterise the trap, and then identify the frequency range over which trap anisotropy influences the data. This approach is initially applied to simulated data for a Newtonian fluid where the trap anisotropy induced maximum error in viscosity is reduced from ~ 150% to less than 6%. The effectiveness of the method is corroborated by experimental MOT measurements performed with water and gelatine solutions, thus confirming that the microrheology of a fluid can be extracted reliably across a wide frequency range and in any arbitrary direction. This work opens the door to fully spatially and angularly resolved 3D mapping of the rheological properties of soft materials over a broad frequency range.

Lipid emulsion structure, digestion behavior, physiology, and health: a scoping review and future directions.

Research investigating the effects of the food matrix on health is needed to untangle many unresolved questions in nutritional science. Emulsion structure plays a fundamental role in this inquiry; however, the effects of oil-in-water emulsion structure on broad metabolic, physiological, and health-related outcomes have not been comprehensively reviewed. This systematic scoping review targets this gap and examines methodological considerations for the field of relating food structure and health. MEDLINE, Web of Science, and CAB Direct were searched from inception to December 2022, returning 3106 articles, 52 of which were eligible for inclusion. Many investigated emulsion lipid droplet size and/or gastric colloidal stability and their relation to postprandial weight-loss-related outcomes. The present review also identifies numerous novel relationships between emulsion structures and health-related outcomes. "Omics" endpoints present an exciting avenue for more comprehensive analysis in this area, yet interpretation remains difficult. Identifying valid surrogate biomarkers for long-term outcomes and disease risk will be a turning point for food structure research, leading to breakthroughs in the pace and utility of research that generates advancements in health. The review's findings and recommendations aim to support new hypotheses, future trial design, and evidence-based emulsion design for improved health and well-being.

Factors associated with return of home oral fluid kits by suspected cases of measles, cohort study, London and South East of England, 2016-2018.

A testing rate for measles above 80% is required by the WHO European Region Measles Elimination strategy to verify elimination. To comply with this rate, we explored factors associated with the return of oral fluid kits (OFK) by suspected measles cases. We described the cases and conducted a mixed-effects analysis to assess the relationship between socio-demographic and public health management characteristics and the likelihood of returning an OFK to the reference laboratory. Of 3,929 cases who were sent a postal OFK, 2,513 (67%) returned the kit. Adjusting for confounding, registration with a general practitioner (GP) (aOR:1.48, 95%CI:1.23-1.76) and living in a less deprived area (aOR:1.35, 95%CI:1.04-1.74) were associated with an increased likelihood of returning the OFK. The odds of returning the OFK also increased if the HPT contacted the parents/guardians of all cases prior to sending the kit and confirmed their address (aOR:2.01, 95%CI:1.17-3.42). Cases notified by a hospital (aOR:1.94, 95%CI:1.31-2.87) or GP (aOR:1.52; 95%CI:1.06-2.16) also had higher odds of returning the OFK. HPTs may want to consider these factors when managing suspected cases of measles since this may help in increasing the testing rates to the WHO-recommended level.

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.

In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to drug resistance. Candidate drug discovery in AML requires advanced synthetic platforms to improve our understanding of the impact of mechanical cues on drug sensitivity in AML. By use of a synthetic, self-assembling peptide hydrogel (SAPH) of modifiable stiffness and composition, a 3D model of the bone marrow niche to screen repurposed FDA-approved drugs has been developed and utilized. AML cell proliferation was dependent on SAPH stiffness, which was optimized to facilitate colony growth. Three candidate FDA-approved drugs were initially screened against the THP-1 cell line and mAF9 primary cells in liquid culture, and EC50 values were used to inform drug sensitivity assays in the peptide hydrogel models. Salinomycin demonstrated efficacy in both an 'early-stage' model in which treatment was added shortly after initiation of AML cell encapsulation, and an 'established' model in which time-encapsulated cells had started to form colonies. Sensitivity to Vidofludimus treatment was not observed in the hydrogel models, and Atorvastatin demonstrated increased sensitivity in the 'established' compared to the 'early-stage' model. AML patient samples were equally sensitive to Salinomycin in the 3D hydrogels and partially sensitive to Atorvastatin. Together, this confirms that AML cell sensitivity is drug- and context-specific and that advanced synthetic platforms for higher throughput are valuable tools for pre-clinical evaluation of candidate anti-AML drugs.

The associations between life events and person-centered personality consistency.

OBJECTIVE: Few environments reliably influence mean-level and rank-order changes in personality-perhaps because personality development needs to be examined through an individualized, person-centered lens. METHODS: The current study used Bayesian multilevel linear models to examine the association between 16 life events and changes in person-centered, Big Five personality consistency across 4 to 10 waves of data using four datasets (N = 24,491). RESULTS: Selection effects were found for events such as marriage, (un)employment, retirement, and volunteering, whereas between-person effects for slopes were found for events such as beginning formal education, employment, and retirement. Within-person changes were often small and emerged inconsistently across datasets but, when present, were brief and negative in direction, suggesting life events can serve as a short-term disruption to the personality system. However, there were many individual differences around event-related trajectories. CONCLUSION: Our results highlight that the effects of life events depend on how personality and its changes are quantified-with these findings underscoring the utility of a person-centered approach as it can capture the full range of these idiosyncrasies. Overall, these findings suggest that life events are associated with a range of idiosyncratic effects and can serve as a short-term, destabilizing shock to one's personality system.

Identifying barriers to utilization of a medication access program among referred patients surveyed after discharge from an acute care hospital.

BACKGROUND: For uninsured residents of select counties in North Carolina, the Cumberland County Medication Access Program (CCMAP) provides prescriptions at no cost. Uninsured patients hospitalized at Cape Fear Valley Medical Center are referred to CCMAP at discharge by Cape Fear Valley Health System employees, primarily coordination of care personnel and outpatient pharmacy personnel. The purpose of this study was to describe the most frequently reported utilization barriers among surveyed patients referred to CCMAP after discharge from Cape Fear Valley Medical Center. METHODS: This was a single-center, survey-based, descriptive research study. Referring Cape Fear Valley Health System employees collected the medical record number of patients referred to CCMAP at discharge between October 22, 2020 and December 31, 2020. These patients were contacted via a research team member by telephone at least 30 days after discharge to voluntarily participate in a survey regarding their ability to receive prescriptions from CCMAP after discharge. Patient-reported utilization barriers and demographics were recorded. A similar survey was voluntarily completed by referring health system employees. Employee-reported utilization barriers were collected to identify discrepancies in perceived utilization barriers among discharged patients and referring health system employees. RESULTS: There were 69 patients referred to CCMAP at discharge by outpatient pharmacy personnel. A total of 17 patients met inclusion criteria and completed the survey. Of these, 35.29% of the patients reported their greatest utilization barrier to be uncertainty about how to apply for CCMAP. In addition, 25 surveys were completed by referring outpatient pharmacy personnel. Of these, 56% of the participants reported they believe the greatest utilization barrier to be patient uncertainty about how to apply for CCMAP. CONCLUSIONS: Uninsured patients discharged from Cape Fear Valley Medical Center could benefit from increased assistance with completing CCMAP applications and enrollment with the program before discharge to improve continuity of care.

Riluzole does not ameliorate disease caused by cytoplasmic TDP-43 in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS, and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43 kDa (TDP-43), and understanding the effects of riluzole in models that closely recapitulate TDP-43 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in female transgenic mice that inducibly express nuclear localisation sequence (NLS)-deficient human TDP-43 in neurons (NEFH-tTA/tetO-hTDP-43ΔNLS, 'rNLS8', mice). Riluzole treatment from the first day of hTDP-43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP-43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8 mice, riluzole did not ameliorate this disease-associated molecular phenotype. Likewise, riluzole did not alter the disease-associated atrophy of hindlimb muscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late-stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre-type changes reminiscent of ALS in female rNLS8 mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways related to accumulation of TDP-43 pathology may be needed to develop better treatments for ALS.

Splicing factor proline and glutamine rich intron retention, reduced expression and aggregate formation are pathological features of amyotrophic lateral sclerosis.

AIM: Splicing factor proline and glutamine rich (SFPQ) is an RNA-DNA binding protein that is dysregulated in Alzheimer's disease and frontotemporal dementia. Dysregulation of SFPQ, specifically increased intron retention and nuclear depletion, has been linked to several genetic subtypes of amyotrophic lateral sclerosis (ALS), suggesting that SFPQ pathology may be a common feature of this heterogeneous disease. Our study aimed to investigate this hypothesis by providing the first comprehensive assessment of SFPQ pathology in large ALS case-control cohorts. METHODS: We examined SFPQ at the RNA, protein and DNA levels. SFPQ RNA expression and intron retention were examined using RNA-sequencing and quantitative PCR. SFPQ protein expression was assessed by immunoblotting and immunofluorescent staining. At the DNA level, SFPQ was examined for genetic variation novel to ALS patients. RESULTS: At the RNA level, retention of SFPQ intron nine was significantly increased in ALS patients' motor cortex. In addition, SFPQ RNA expression was significantly reduced in the central nervous system, but not blood, of patients. At the protein level, neither nuclear depletion nor reduced expression of SFPQ was found to be a consistent feature of spinal motor neurons. However, SFPQ-positive ubiquitinated protein aggregates were observed in patients' spinal motor neurons. At the DNA level, our genetic screen identified two novel and two rare SFPQ sequence variants not previously reported in the literature. CONCLUSIONS: Our findings confirm dysregulation of SFPQ as a pathological feature of the central nervous system of ALS patients and indicate that investigation of the functional consequences of this pathology will provide insight into ALS biology.

Effect of pH and heat treatment conditions on physicochemical and acid gelation properties of liquid milk protein concentrate.

Milk protein concentrates (MPC) are typically dried high-protein powders with functional and nutritional properties that can be tailored through modification of processing conditions, including temperature, pH, filtration, and drying. However, the effects of processing conditions on the structure-function properties of liquid MPC (fluid ultrafiltered milk), specifically, are understudied. In this report, the pH of liquid MPC [13% protein (70% protein DM basis), pH 6.7] was adjusted to 6.5 or 6.9, and samples at pH 6.5, 6.7, and 6.9 were subjected to heat treatment at either 85°C for 5 min or 125°C for 15 s. Sodium dodecyl sulfate PAGE was used to determine the distribution of caseins and denatured whey proteins in the soluble and micellar phases, and HPLC was used to quantify native whey proteins as a measure of denaturation, based on the processing conditions. Both heat treatments resulted in substantial whey protein denaturation at each pH, with ß-lactoglobulin denatured more extensively than α-lactalbumin. Changes in liquid MPC physicochemical properties were monitored at d 1, 5, and 8 during storage at 4°C. Viscosity increased after heat treatment and also over time, regardless of pH and heating conditions, suggesting the role of whey protein denaturation and aggregation, and their interactions with casein micelles. The MPC samples processed at pH 6.9 had a significantly higher viscosity than those heated at pH 6.5 or 6.7, for both temperature and time conditions; and samples processed at 85°C for 5 min had higher viscosity than those heated at 125°C for 15 s. Particle size analysis indicated the presence of larger particles after 5 and 8 d of MPC storage after heating at pH 6.9. Acid-induced gelation of the liquid MPC led to significantly higher gel firmness after processing at 85°C for 5 min, compared with 125°C for 15 s. Also, gels made from MPC adjusted to pH 6.5 had higher storage moduli, with both time and temperature combinations, demonstrating the role of pH-dependent association of denatured whey proteins with casein micelles in gel network formation. These findings enable a better understanding of the processing factors contributing to structural and functional properties of liquid MPC and can be helpful in tailoring milk protein ingredient functionality for a variety of food products.

Impact of health system protocol on patient qualification for influenza point-of-care testing.

BACKGROUND: Point-of-care testing (POCT) is a service that community pharmacies are implementing to increase patient access to care. Many pharmacies develop protocols with physicians to maximize patient qualification for POCT, while maintaining patient safety. OBJECTIVE: To determine the number of patients seen for influenza in the emergency department (ED) during the 2018-2019 season who would qualify for protocol-driven influenza testing. METHODS: This was a retrospective review of medical records. Patients seen in this 92 bed ED, level III trauma center between October 1, 2018 and May 1, 2019 were included if their age was older than 11 years or younger than 71 years with an influenza-related diagnosis. Patients were excluded if they were pregnant or breastfeeding, were allergic to oseltamivir, were recently diagnosed with pneumonia, or recently received a live influenza vaccine. Patient information collected included: sex, age, height, weight, pulse, blood pressure, respiratory rate, temperature, oxygen saturation, mental status, symptoms, time since onset of symptoms, immune system status, and history of respiratory illness or respiratory disease. These data points were used to determine eligibility for POCT based on a prespecified protocol that included criteria such as vital signs, symptom presentation, and other health conditions. The primary end point was the number of patients eligible for institutional protocol-driven POCT. RESULTS: There were 1955 ED visits with a primary diagnosis of influenza; 451 were eligible for study inclusion, and 49 (11%) qualified for POCT. The most common reason that patients did not qualify was temperature. If required temperature had been removed from the protocol, 155 patients (34%) would have qualified for POCT. CONCLUSION: On the basis of the institutional protocol, a small proportion of patients qualified for POCT. Without the protocol temperature requirement, the number of patients who qualified for POCT would have greatly increased. This study identified opportunities for improvement in the institutional protocol. Future research is needed to reassess the number of patients who qualify once revisions are made.

Emulsion Droplet Crystallinity Attenuates Short-Term Satiety in Healthy Adult Males: A Randomized, Double-Blinded, Crossover, Acute Meal Study.

BACKGROUND: The influence of triacylglycerol (TAG) physical properties on satiety remains poorly understood. OBJECTIVES: The objective was to investigate if and how TAG digestion and absorption, modulated only by differences in TAG crystallinity, would differentially affect short-term satiety in healthy men. METHODS: We tempered 500 mL 10% palm stearin oil-in-water emulsions such that the lipid droplets were either undercooled liquid (LE) or partially crystalline solid (SE). Fifteen healthy men (mean ± SD age: 27.5 ± 5.7 y; BMI: 24.1 ± 2.5 kg/m2; fasting TAG: 0.9 ± 0.3 mmol/L) consumed each beverage at two 6-h study visits separated by ≥6 d after an overnight fast, along with 1500 mg acetaminophen suspended in water. The participants characterized the emulsion sensory properties, completed satiety visual analog scale ratings, and had serial blood samples collected for 6-h analysis of plasma peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, leptin, glucose-dependent insulinotropic polypeptide (GIP), insulin, and acetaminophen (for assessing gastric emptying). Repeated-measures ANOVAs and 2-tailed paired t tests were used to analyze the changes from baseline and incremental area under the curve (iAUC) values, respectively. RESULTS: With consumption of LE compared with SE, there was a 358% higher fullness (P = 0.015) and a 103% lower average appetite (P = 0.041) score, along with higher iAUC values for PYY (P = 0.011) and GLP-1 (P = 0.028) (103% and 66% higher, respectively), but not for ghrelin (P = 0.39), based on change from baseline values. Acetaminophen response trended toward significance (P = 0.08) and was 15% higher with LE. SE was rated as 44% thicker (P = 0.034) and 24% creamier (P = 0.05) than LE. CONCLUSIONS: The suppression of TAG digestion by the presence of partially crystalline lipid droplets blunted the appetite-suppressing effects of an oil-in-water emulsion.This trial was registered at clinicaltrials.gov as NCT03990246.

Emulsion Droplet Crystallinity Attenuates Postprandial Plasma Triacylglycerol Responses in Healthy Men: A Randomized Double-Blind Crossover Acute Meal Study.

BACKGROUND: The presence of triacylglycerol (TAG) cystallinity is assumed to influence digestibility and postprandial lipemia (PPL), although studies to date are limited. OBJECTIVE: This study aimed to investigate whether the presence of solid fat compared with undercooled liquid oil, specifically, plays a role in determining PPL by comparing emulsion droplets differing only in terms of physical state. METHODS: Ten percent palm stearin and 0.4% sorbitan monostearate emulsions were tempered to contain identically sized, charged, and shaped (spherical) undercooled liquid (LE) compared with partially crystalline solid (SE; mean ± SEM: 33.2% ± 0.03% solid fat at 37°C) droplets. Fifteen healthy fasting adult men (mean ± SD age: 27.5 ± 5.7 y; BMI: 24.1 ± 2.5 kg/m2) consumed 500 mL of each emulsion on separate occasions and plasma TAG concentrations, particle size of the plasma chylomicron-rich fraction (CMRF), and fatty acid (FA) composition of the CMRF-TAG were serially determined in a 6-h postprandial randomized double-blind crossover acute meal study. Changes from baseline values were analyzed by repeated-measures ANOVA. RESULTS: An earlier (2 compared with 3 h, P < 0.05) significant rise, a 39.9% higher mean postprandial TAG change from baseline (P = 0.08), and higher peak concentration (mean ± SEM: 1.47 ± 0.19 compared with 1.20 ± 0.15 mmol/L, P = 0.04) and iAUC (1.95 ± 0.39 compared with 1.45 ± 0.31 mmol/L × h, P = 0.03) values were observed for LE compared with SE. The compositions of the CMRF-TAG FAs shifted toward those of the ingested palm stearin by 4 h but did not differ between SE and LE (P = 0.90). Nor were there differences in postprandial changes in CMRF particle size (P = 0.79) or nonesterified FAs (P = 0.72) based on lipid physical state. CONCLUSIONS: Despite their identical compositions and colloidal properties, differences in lipid absorption were observed between SE and LE in healthy adult men. This is direct evidence that TAG physical state contributes to PPL, with the presence of solid fat having an attenuating influence.This trial was registered at clinicaltrials.gov as NCT03515590.

Role of Amino Acids in Blood Glucose Changes in Young Adults Consuming Cereal with Milks Varying in Casein and Whey Concentrations and Their Ratio.

BACKGROUND: Increasing the total protein content and reducing the casein to whey ratio in milks consumed with breakfast cereal reduce postprandial blood glucose (BG). OBJECTIVES: We aimed to explore associations between plasma amino acids (AAs), BG, and glucoregulatory hormones. METHODS: In this repeated-measures design, 12 healthy adults consumed cereal (58 g) and milks (250 mL) with 3.1 wt% or high 9.3 wt% protein concentrations and with casein to whey ratios of either 80:20 or 40:60. Blood was collected at 0, 30, 60, 120, 140, 170, and 200 min for measurement of the primary outcome, BG, and for the exploratory outcomes such as plasma AA, gastric emptying, insulin (INS), and glucoregulatory hormones. Measures were made prior to and after an ad libitum lunch at 120 min. Exploratory correlations were conducted to determine associations between outcomes. RESULTS: Pre-lunch plasma AA groups [total (TAA), essential (EAA), BCAA, and nonessential (NEAA)] were higher after 9.3 wt% than 3.1 wt% milks by 12.7%, 21.4%, 20.9%, and 7.6%, respectively (P ≤ 0.05), while post-lunch AA groups were higher by 10.9%, 19.8%, 18.8%, and 6.0%, respectively (P ≤ 0.05). Except for NEAA, pre-lunch AAs were higher after 40:60 than 80:20 ratio milks by 4.5%, 8.3%, and 9.3% (P ≤ 0.05). When pooled by all treatments, pre-lunch AA groups associated negatively with BG (r/ρ ≥ -0.45, P ≤ 0.05), but post-lunch only TAA and NEAA correlated (r ≥ -0.37, P < 0.05). Pre-lunch BG was inversely associated with Leu, Ile, Lys, Met, Thr, Cys-Cys, Asn, and Gln (r/ρ ≥ -0.46, P ≤ 0.05), but post-lunch, only with Thr, Ala, and Gly (r ≥ -0.50, P ≤ 0.05). Pre-lunch associations between AA groups and INS were not found. CONCLUSIONS: Protein concentration and the ratio of casein to whey in milks consumed at breakfast with cereal affect plasma AA concentrations and their associations with decreased BG. The decrease in BG could be explained by INS-independent mechanisms. This trial was registered at www.clinicaltrials.gov as NCT02471092.

Acute whole apple consumption did not influence postprandial lipaemia: a randomised crossover trial.

Whole apples are a source of pectin and polyphenols, both of which show potential to modulate postprandial lipaemia (PPL). The present study aimed to explore the effects of whole apple consumption on PPL, as a risk factor for CVD, in generally healthy but overweight and obese adults. A randomised, crossover acute meal trial was conducted with seventeen women and nine men (mean BMI of 34·1 (sem 0·2) kg/m2). Blood samples were collected for 6 h after participants consumed an oral fat tolerance test meal that provided 1 g fat/kg body weight and 1500 mg acetaminophen per meal for estimating gastric emptying, with and without three whole raw Gala apples (approximately 200 g). Plasma TAG (with peak postprandial concentration as the primary outcome), apoB48, chylomicron-rich fraction particle size and fatty acid composition, glucose, insulin and acetaminophen were analysed. Differences between with and without apples were identified by ANCOVA. Apple consumption did not alter postprandial TAG response, chylomicron properties, glucose or acetaminophen (P > 0·05), but did lead to a higher apoB48 peak concentration and exaggerated insulin between 20 and 180 min (P < 0·05). Overall, as a complex food matrix, apples did not modulate postprandial TAG when consumed with a high-fat meal in overweight and obese adults, but did stimulate insulin secretion, potentially contributing to an increased TAG-rich lipoprotein production.

Consumption of whole purple and regular wheat modestly improves metabolic markers in adults with elevated high-sensitivity C-reactive protein: a randomised, single-blind parallel-arm study.

Whole-grain wheat, in particular coloured varieties, may have health benefits in adults with chronic metabolic disease risk factors. Twenty-nine overweight and obese adults with chronic inflammation (high-sensitivity C-reactive protein) > 1·0 mg/l) replaced four daily servings of refined grain food products with bran-enriched purple or regular whole-wheat convenience bars (approximately 41-45 g fibre, daily) for 8 weeks in a randomised, single-blind parallel-arm study where body weight was maintained. Anthropometrics, blood markers of inflammation, oxidative stress, and lipaemia and metabolites of anthocyanins and phenolic acids were compared at days 1, 29 and 57 using repeated-measures ANOVA within groups and ANCOVA between groups at day 57, with day 1 as a covariate. A significant reduction in IL-6 and increase in adiponectin were observed within the purple wheat (PW) group. TNF-α was lowered in both groups and ferulic acid concentration increased in the regular wheat (RW) group. Comparing between wheats, only plasma TNF-α and glucose differed significantly (P < 0·05), that is, TNF-α and glucose decreased with RW and PW, respectively. Consumption of PW or RW products showed potential to improve plasma markers of inflammation and oxidative stress in participants with evidence of chronic inflammation, with modest differences observed based on type of wheat.

Expansion of pharmacist practice in oral oncolytic therapy with a collaborative practice agreement.

INTRODUCTION: Collaborative practice agreements have been utilized to expand pharmacist roles and improve patient care outcomes. A need to reduce the time providers spend reviewing oral oncolytic prescriptions for therapy continuation or dose adjustments was identified in the oncology clinics of a community health system. A collaborative practice agreement was created to decrease turnaround time for processing oral oncolytic prescriptions, improve provider satisfaction, and decrease patient prescription costs. METHODS: A three-month pilot was initiated to evaluate feasibility and provider satisfaction by comparing two provider groups. An additional three months of data were collected post-collaborative practice agreement implementation to evaluate impact. Primary endpoints included: interventions, turnaround time, and patient cost savings. A survey was conducted to determine provider satisfaction. RESULTS: The mean turnaround time for pharmacist interventions in the pilot group (n = 54) was 7 min, compared to 3311 min in the control group (n = 87), which was statistically significant (p < 0.0001). Two interventions in the pilot group resulted in patient cost savings due to dose rounding by a pharmacist. The mean turnaround time of the post-collaborative practice agreement group (n = 197) was 6 min, which was statistically significant when compared to the control group (p < 0.0001). CONCLUSION: Turnaround time was significantly shorter for prescriptions in the pilot and post-collaborative practice agreement groups compared to the control group. Provider satisfaction increased as the collaborative practice agreement resulted in less time reviewing oral oncolytic prescriptions. Patient costs were also reduced during the pilot phase due to dose rounding by pharmacists.

High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice.

Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD). HFHSD-fed mice rapidly exhibited metabolic alterations, including obesity, hyperleptinemia, physical inactivity, glucose intolerance, peripheral insulin resistance, fasting hyperglycemia, ectopic lipid deposition, and bone deterioration. Prolonged exposure to HFHSD resulted in morbid obesity, ectopic triglyceride deposition in liver and muscle, extensive bone loss, sarcopenia, hyperinsulinemia, and impaired short-term memory. Although many of these defects are typically associated with aging, HFHSD did not alter telomere length in white blood cells, indicating that this diet did not generally promote all aspects of aging. Strikingly, glucose homeostasis was highly dynamic. Glucose intolerance was evident in HFHSD-fed mice after 1 week and was maintained for 24 weeks. Beyond 24 weeks, however, glucose tolerance improved in HFHSD-fed mice, and by 60 weeks, it was indistinguishable from that of chow-fed mice. This improvement coincided with adaptive ß-cell hyperplasia and hyperinsulinemia, without changes in insulin sensitivity in muscle or adipose tissue. Assessment of insulin secretion in isolated islets revealed that leptin, which inhibited insulin secretion in the chow-fed mice, potentiated glucose-stimulated insulin secretion in the HFHSD-fed mice after 60 weeks. Overall, the excessive calorie intake was accompanied by deteriorating function of numerous physiological systems.