Immunomodulation by xylan and carrageenan-type polysaccharides from red seaweeds: Anti-inflammatory, wound healing, cytoprotective, and anticoagulant activities.

The immunomodulatory properties of the polysaccharides (carrageenan, xylan) from Chondrus crispus (CC), Ahnfeltiopsis devoniensis (AD), Sarcodiotheca gaudichaudii (SG) and Palmaria palmata (PP) algal species were studied. Using RAW264.7 macrophages, we investigated the proliferation and migration capacity of different extracts along with their immunomodulatory activities, including nitric oxide (NO) production, phagocytosis, and secretion of pro-inflammatory cytokines. Polysaccharides from C. crispus and S. gaudichaudii effectively mitigated inflammation and improved scratch-wound healing. Polysaccharide fractions extracted under cold conditions (25 °C), including CC-1A, SG-1A and SG-1B stimulated cell proliferation, while fractions extracted under hot conditions (95 °C), including CC-3A, CC-2B and A. devoniensis (AD-3A), inhibited cell proliferation after 48 h. Furthermore, RAW264.7 cells treated with the fractions CC-3A, AD-1A, and SG-2A significantly reduced LPS-stimulated NO secretion over 24 h. Phagocytosis was significantly improved by treatment with C. crispus (CC-2B, CC-3B) and A. devoniensis (AD-3A) fractions. RAW264.7 cells treated with the CC-2A and SG-1A fractions showed elevated TGF-ß1 expression without affecting TNF-α expression at 24 h. Polysaccharide fractions of A. devoniensis (ι/κ hybrid carrageenan; AD-2A, AD-3A) showed the highest anti-coagulation activity. CC-2A and SG-1A fractions enhanced various bioactivities, suggesting they are candidates for skin-health applications. The carrageenan fractions (CC-3A: λ-, µ-carrageenan, SG-2A: ν-, ι-carrageenan) tested herein showed great potential for developing anti-inflammatory and upscaled skin-health applications.

Development of hydrogel-based composite scaffolds containing eggshell particles for bone regeneration applications.

This study describes the development and characterization of novel composite scaffolds, made of an alginate-chitosan hydrogel matrix containing eggshell (ES) particles, for bone tissue engineering applications. Scaffolds with ES particles, either untreated or treated with phosphoric acid to create a nanotextured particle surface, were compared to scaffolds without particles. Results indicate that the nanotexturing process exposed occluded ES proteins orthologous to those in human bone extracellular matrix. Scaffolds with ES or nanotextured ES (NTES) particles had a higher porosity (81 ± 4% and 89 ± 5%, respectively) than scaffolds without particles (59 ± 5%) (p = .002 and p < .001, respectively). Scaffolds with NTES particles had a larger median pore size (113 µm [interquartile range [IQ]: 88-140 µm]) than scaffolds with ES particles (94 µm [IQ: 75-112 µm]) and scaffolds without particles (99 µm [IQ: 74-135 µm]) (p < .001 and p = .011, respectively). The compressive modulus of the scaffolds with ES or NTES particles remained low (3.69 ± 0.70 and 3.14 ± 0.62 kPa, respectively), but these scaffolds were more resistant to deformation following maximum compression than those without particles. Finally, scaffolds with ES or NTES particles allowed better retention of human mesenchymal stem cells during seeding (53 ± 12% and 57 ± 8%, respectively, vs. 17 ± 5% for scaffolds without particles; p < .001 in both cases), as well as higher cell viability up to 21 days of culture (67 ± 17% and 61 ± 11%, respectively, vs. 15 ± 7% for scaffolds without particles; p < .001 in both cases). In addition, alkaline phosphatase (ALP) activity increased up to 558 ± 164% on day 21 in the scaffolds with ES particles, and up to 567 ± 217% on day 14 in the scaffolds with NTES particles (p = .006 and p = .002, respectively, relative to day 0). Overall, this study shows that the physicochemical properties of the alginate-chitosan hydrogel scaffolds with ES or NTES particles are similar to those of cancellous bone. In addition, scaffolds with particles supported early osteogenic differentiation and therefore represent a promising new bone substitute, especially for non-load bearing applications.

Pain symptoms and physical performance in older adults: cross-sectional findings from the International Mobility in Aging Study (IMIAS).

PURPOSE: To analyze the associations between pain and physical performance in different aging contexts. METHODS: Data from 1725 older adults from Canada, Brazil, Colombia, and Albania from the 2014 wave of the IMIAS were used to assess the associations between Back Pain (BP) or Lower Limb Pain (LLP) and physical performance by the Short Physical Performance Battery (SPPB). Three binary logistic regression models adjusted for sex, age, study site, education, income sufficiency, BMI, depressive symptoms, and chronic conditions were used to estimate the associations between LLP or BP and SPPB. The SPPB was classified into good performance (8 points or more) and poor physical performance (< 8 points). RESULTS: The mean age of the older men was 71.2 (± 3.0) and the mean age of the women was 71.2 (± 2.8) years. Older men (72.8%, p < 0.05) and women (86.1%, p-value < 0.05) from Albania had the highest frequencies of self-reported general pain. Older women in Colombia had the highest frequencies of LLP or BP (33.5%, p-value < 0.05). In the fully adjusted logistic regression model, LLP or BP was significantly associated with poor SPPB (OR = 0.48, 0.35 to 0.66 95% CI, p < 0.01). CONCLUSIONS: Pain symptoms are associated with reduced physical performance in older people, even when adjusted for other clinical and sociodemographic factors. Protocols for aiming to increase the level of physical activity to manage pain should be incorporated into health care strategies.

A Two Bacteriocinogenic Ligilactobacillus Strain Association Inhibits Growth, Adhesion, and Invasion of Salmonella in a Simulated Chicken Gut Environment.

In this study, we aimed to develop a protective probiotic coculture to inhibit the growth of Salmonella enterica serovar Typhimurium in the simulated chicken gut environment. Bacterial strains were isolated from the digestive mucosa of broilers and screened in vitro against Salmonella Typhimurium ATCC 14028. A biocompatibility coculture test was performed, which identified two biocompatible strains, Ligilactobacillus salivarius UO.C109 and Ligilactobacillus saerimneri UO.C121 with high inhibitory activity against Salmonella. The cell-free supernatant (CFS) of the selected isolates exhibited dose-dependent effects, and the inhibitory agents were confirmed to be proteinaceous by enzymatic and thermal treatments. Proteome and genome analyses revealed the presence of known bacteriocins in the CFS of L. salivarius UO.C109, but unknown for L. saerimneri UO.C121. The addition of these selected probiotic candidates altered the bacterial community structure, increased the diversity of the chicken gut microbiota challenged with Salmonella, and significantly reduced the abundances of Enterobacteriaceae, Parasutterlla, Phascolarctobacterium, Enterococcus, and Megamonas. It also modulated microbiome production of short-chain fatty acids (SCFAs) with increased levels of acetic and propionic acids after 12 and 24 h of incubation compared to the microbiome challenged with S. Typhimurium. Furthermore, the selected probiotic candidates reduced the adhesion and invasion of Salmonella to Caco-2 cells by 37-39% and 51%, respectively, after 3 h of incubation, compared to the control. These results suggest that the developed coculture probiotic strains has protective activity and could be an effective strategy to control Salmonella infections in poultry.

Comparison of corneal measurements in normal and keratoconus eyes using Anterior Segment Optical Coherence Tomography (AS-OCT) and Pentacam HR topographer.

BACKGROUND: Keratoconus (KC) is easily recognized by its unique topographic pattern, but it can be difficult to distinguish subclinical form of the disease from the normal cornea. Optovue anterior segment optical coherence tomography (AS-OCT) helps diagnose KC. AIM OF THE WORK: To assess and the level of agreement of Keratometry-readings (K), Central Corneal Thickness (CCT) and Thinnest Corneal Thickness (TCT) measurements obtained by Optovue AS-OCT and Wavelight Oculyzer Pentacam HR in two groups: KC eyes and normal eyes. PATIENTS AND METHODS: This is a prospective clinical observational study. The study included 110 eyes divided into two groups. The study group included 62 eyes with topographic evidence of KC. The control group included 48 eyes of normal subjects with no topographic evidence of KC. All of the participants underwent full cycloplegic refraction, spectacle best-corrected distance visual acuity, comprehensive slit-lamp biomicroscopy and fundoscopy. All participants underwent corneal topography by Pentacam HR and AS-OCT. RESULTS: There were highly significant differences between the studied groups as regarding BCVA, intraocular pressure and CCT measurements which were found to be lower among KC group compared to the control one. There were highly significant differences between the studied groups regarding TCT measurement detected by Pentacam HR and AS-OCT which was found to be lower among the keratoconus group compared to the control one (470.9, 455.7 versus 541.9 and 518.7 respectively). CONCLUSION: Both Scheimpflug-based imaging and AS-OCT provide comparable readings with a good agreement regarding corneal pachymetry in keratoconus group with accurate identification of KC eyes and healthy ones. However, there was a significant difference in K readings between both devices in Keratoconus and control group.

The association between anemia and depression in older adults and the role of treating anemia.

OBJECTIVES: To investigate the association between anemia and depression and whether the treatment of anemia modifies the effect of the association between anemia and depression. METHODS: This secondary data analysis is based on data from the Enquête sur la santé des aînés (ESA)-Services study conducted in 2011-2013 on community-dwelling older adults recruited in primary care and have given access to their medico-administrative data (n = 1447). The presence of anemia was self-reported, as was depression (major and minor) aligned with symptoms of the DSM-5. Treated anemia was based on the presence of medications delivered to participants. Cross-sectional associations were analyzed using multivariable logistic regression, controlling for confounders. RESULTS: The prevalence of self-reported anemia in our sample was estimated at 6.7%. Self-reported anemia was associated with increased odds of depression. Individuals with untreated anemia had a 2.6-fold increased odds of depression compared to those with no anemia. In contrast, the odds of depression in individuals with treated anemia were not different from individuals with no anemia. CONCLUSION: The findings underline the importance of treating anemia in older adults. Future longitudinal studies are needed to replicate the findings and further explore the role of treating anemia on symptoms of depression.

Allostatic load and physical performance in older adults: Findings from the International Mobility in Aging Study (IMIAS).

OBJECTIVE: This study aimed to evaluate the association between Allostatic Load (AL) and physical performance scores in older adults from four cities in North and South America. METHODS: In this cross-sectional study, data from 1101 volunteers from three countries (Canada, Brazil, and Colombia) from the International Mobility in Aging Study (IMIAS) were used to evaluate the association between AL index and Short Physical Performance Battery (SPPB) scores. Three multiple linear regression models adjusted by age, Socioeconomic Status (SES), chronic conditions, depression symptoms, and Leganés Cognitive Test (LCT) were developed to estimate the independent association between SPPB and AL. Mediation analysis with 2012 LA data and covariates was performed to access the total, direct, and indirect effects of mediation on SPPB scores from 2016. RESULTS: AL and SPPB were inversely associated, with older adults with high allostatic load scoring lower on SPPB (ß: -0.234, Std: 0.033, p-value: <0.001).  Indirect effects were evidenced between age, SES and chronic conditions with AL and SPPB scores. Chronic conditions also had a total effect on SPPB scores and were also mediated by AL. However, indirect effects of depressive symptoms and LCT on SPPB scores mediated by AL were not observed. CONCLUSIONS: Findings from this study support that increased AL index determines worse physical performance states after full adjustments. AL has a mediator role between the number of chronic diseases, depressive symptoms, cognitive status and physical performance. Socioeconomic status also influenced physical scores mediated by the AL index.

HbA1c and physical performance in older adults from different aging epidemiological contexts: Longitudinal findings of the International Mobility in Aging Study (IMIAS).

OBJECTIVE: This study aimed to assess the longitudinal predictions between glycated hemoglobin A1c (HbA1c) and physical performance scores in different epidemiological contexts of aging. MATERIAL AND METHODS: Longitudinal data of 1,337 older people from three countries (Canada, Brazil and Colombia) of the International Mobility in Aging Study (IMIAS) were used to assess the relationship between HbA1c and Short Physical Performance Battery (SPPB) scores between 2012 and 2016. Linear Mixed Models grouped by sex and adjusted by Age, Study site, Chronic Conditions, Anthropometric Measures, and Inflammatory Level were used to estimate the influence of HbA1c and covariates on SPPB scores. RESULTS: At the IMIAS baseline, Latin American (LA) cities had higher HbA1c averages compared to Canadian cities, with Natal (Brazil) being the city with the highest HbA1c averages in men and women (6.32 ± 1.49; 6,56 ± 1.70 respectively). SPPB scores were significantly lower in LA cities, and older people in Natal had lower SPPB averages in men (9.67 ± 2.38; p-value < 0.05) and women (8.52 ± 2.33; p-value <0.05). In the multivariate mixed linear models of longitudinal analyses, HbA1c was significantly associated with lower SPPB scores in men (ß = -0.25, 95% CI: -0.39 to -0.12, p-value = 0.02) but not in women. CONCLUSION: High HbA1c levels at baseline were longitudinally associated in older adults from different countries, and this association was observed only in men and not in women. This study highlights a possible influence of gender on this relationship.

Roux-en-Y gastric bypass alters intestinal glucose transport in the obese Zucker rat.

Introduction: The gastrointestinal tract plays a major role in regulating glucose homeostasis and gut endocrine function. The current study examines the effects of Roux-en-Y gastric bypass (RYGB) on intestinal GLP-1, glucose transporter expression and function in the obese Zucker rat (ZR). Methods: Two groups of ZRs were studied: RYGB and sham surgery pair-fed (PF) fed rats. Body weight and food intake were measured daily. On post-operative day (POD) 21, an oral glucose test (OGT) was performed, basal and 30-minute plasma, portal venous glucose and glucagon-like peptide-1 (GLP-1) levels were measured. In separate ZRs, the biliopancreatic, Roux limb (Roux) and common channel (CC) intestinal segments were harvested on POD 21. Results: Body weight was decreased in the RYGB group. Basal and 30-minute OGT plasma and portal glucose levels were decreased after RYGB. Basal plasma GLP-1 levels were similar, while a 4.5-fold increase in GLP-1 level was observed in 30-minute after RYGB (vs. PF). The increase in basal and 30-minute portal venous GLP-1 levels after RYGB were accompanied by increased mRNA expressions of proglucagon and PC 1/3, GPR119 protein in the Roux and CC segments. mRNA and protein levels of FFAR2/3 were increased in Roux segment. RYGB decreased brush border glucose transport, transporter proteins (SGLT1 and GLUT2) and mRNA levels of Tas1R1/Tas1R3 and α-gustducin in the Roux and CC segments. Conclusions: Reductions in intestinal glucose transport and enhanced post-prandial GLP-1 release were associated with increases in GRP119 and FFAR2/3 after RYGB in the ZR model. Post-RYGB reductions in the regulation of intestinal glucose transport and L cell receptors regulating GLP-1 secretion represent potential mechanisms for improved glycemic control.

Proteomic Analysis of Chicken Chorioallantoic Membrane (CAM) during Embryonic Development Provides Functional Insight.

In oviparous animals, the egg contains all resources required for embryonic development. The chorioallantoic membrane (CAM) is a placenta-like structure produced by the embryo for acid-base balance, respiration, and calcium solubilization from the eggshell for bone mineralization. The CAM is a valuable in vivo model in cancer research for development of drug delivery systems and has been used to study tissue grafts, tumor metastasis, toxicology, angiogenesis, and assessment of bacterial invasion. However, the protein constituents involved in different CAM functions are poorly understood. Therefore, we have characterized the CAM proteome at two stages of development (ED12 and ED19) and assessed the contribution of the embryonic blood serum (EBS) proteome to identify CAM-unique proteins. LC/MS/MS-based proteomics allowed the identification of 1470, 1445, and 791 proteins in CAM (ED12), CAM (ED19), and EBS, respectively. In total, 1796 unique proteins were identified. Of these, 175 (ED12), 177 (ED19), and 105 (EBS) were specific to these stages/compartments. This study attributed specific CAM protein constituents to functions such as calcium ion transport, gas exchange, vasculature development, and chemical protection against invading pathogens. Defining the complex nature of the CAM proteome provides a crucial basis to expand its biomedical applications for pharmaceutical and cancer research.

Novel easily separable core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent: optimization of phosphorus removal from Fosfomycin pharmaceutical wastewater.

A new easily separable core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent was synthesized and then examined for removal of Fosfomycin antibiotic from synthetic pharmaceutical wastewater. The removal process of Fosfomycin was expressed through testing the total phosphorus (TP). A response surface model (RSM) for Fosfomycin adsorption (as mg-P L-1) was used by carrying out the experiments using a central composite design. The adsorption model showed that Fosfomycin adsorption is directly proportional to core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent dosage and time, and indirectly to initial Fosfomycin concentration. The removal increased by decreasing the pH to 2. The Fosfomycin removal was done at room temperature under an orbital agitation speed of 250 rpm. The adsorption capacity of core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent reached around 1200 mg-P g-1, which is significantly higher than other MOF adsorbents reported in the literature. The maximum Langmuir adsorption capacity of the adsorbent for Fosfomycin was 126.58 mg g-1 and Fosfomycin adsorption behavior followed the Freundlich isotherm (R 2 = 0.9505) in the present study. The kinetics was best fitted by the pseudo-second-order model (R 2 = 0.9764). The RSM model was used for the adsorption process in different target modes.

Trajectories of Frailty With Aging: Coordinated Analysis of Five Longitudinal Studies.

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasive E. coli and H2S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.

Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders.

CDK4/6 inhibitors (CDK4/6i) are effective in metastatic breast cancer, but they have been only modestly effective in most other tumor types. Here we show that tumors expressing low CDK6 rely on CDK4 function, and are exquisitely sensitive to CDK4/6i. In contrast, tumor cells expressing both CDK4 and CDK6 have increased reliance on CDK6 to ensure cell cycle progression. We discovered that CDK4/6i and CDK4/6 degraders potently bind and inhibit CDK6 selectively in tumors in which CDK6 is highly thermo-unstable and strongly associated with the HSP90/CDC37 complex. In contrast, CDK4/6i and CDK4/6 degraders are ineffective in antagonizing tumor cells expressing thermostable CDK6, due to their weaker binding to CDK6 in these cells. Thus, we uncover a general mechanism of intrinsic resistance to CDK4/6i and CDK4/6i-derived degraders and the need for novel inhibitors targeting the CDK4/6i-resistant, thermostable form of CDK6 for application as cancer therapeutics.

Biotechnological Applications of Eggshell: Recent Advances.

The eggshell (ES) provides protection against pathogenic and physical insults while supplying essential metabolic and nutritional needs for the growing avian embryo. It is constituted mainly of calcium carbonate arranged as calcite crystals. The global chicken egg production in 2018 was over 76.7 million metric tons. In industrialized countries, about 30% of eggs are processed at breaker plants that produce liquid egg products and large quantities of solid ES waste. ES waste is utilized for a variety of low-value applications, or alternatively is disposed in landfill with associated economic and environmental burdens. The number of patents pertaining to ES applications has increased dramatically in recent years; of 673 patents granted in the last century, 536 (80%) were published in the last two decades. This review provides a snapshot of the most recent patents published between 2015 and 2020, with emphasis on different biotechnological applications of ES waste, and summarizes applications for biomedical, chemical, engineering, and environmental technologies. Biomedical technologies include the production of calcium lactate, calcium phosphate, and health-promoting products, while chemical technologies include plant growth promoters, food processing and production, and biodiesel oil catalysis along with active calcium, carbon, soluble proteins, organic calcium, and ultrafine calcium carbonate sources. Engineering technologies address material engineering and nanoparticle production, while environmental technologies pertain to production of biomass, solubilization of sludge as well as production of magnetic ES adsorbents and adsorption of heavy metals, organics, total nitrogen and fluoride, soil pollutants, and radioactive compounds. Although the number of ES-based patents has exponentially increased in the last decade, exploration of innovative top-down approaches and ES development as a physical platform are new endeavors that are expected to further increase the upscaling of ES waste exploitation.

Chronic Neutrophilic Leukemia with Monocytosis.

Chronic neutrophilic leukaemia is a very rare disease with diagnosis based on persistent leucocytosis >25×103/µl and monocytes <1×103/µl. The revised WHO criteria 2016 included CSF3R gene mutations as a diagnostic finding. We report the case of a 77-year-old man who was found to have asymptomatic persistent mature neutrophilic leucocytosis with monocytosis. Molecular study confirmed the presence of a CSF3R gene mutation in the absence of morphological or genetic features of myelodysplasia or other forms of myelodysplastic syndrome. The patient's medical history was significant for coronary artery disease, hypertension, chronic obstructive pulmonary disease, bilateral cystic bronchiectasis, moderate pulmonary hypertension, tuberculosis treated 27 years previously, hypothyroidism, and a thyroid nodule. He had hepatosplenomegaly but no lymphadenopathy, and no other malignancy was seen on computed tomography (CT) scanning. At the time of evaluation, he was free of symptoms and had no evidence of infection or drug-induced leucocytosis. The patient was referred to an oncology centre and treated with hydroxyurea and subsequently azacitidine. However, he developed pancytopenia with bone marrow aplasia. He died with neutropenia sepsis. The presence of persistent monocytosis in this case created a diagnostic dilemma as to whether the disease was a variant of chronic neutrophilic leukaemia or was reactive monocytosis. LEARNING POINTS: The presence of a CSF3R gene mutation is diagnostic for chronic neutrophilic leukaemia (CNL).The monocytosis in this patient might have been a new variant of CNL.

A Survey of Recent Patents in Engineering Technology for the Screening, Separation and Processing of Eggshell.

The chicken egg is a well-known complete food of human daily consumption which serves as a cost-effective, high-quality nutrient resource. About 30% of table eggs are directed to breaker plants in developed countries, leading to the generation of substantial eggshell (ES) waste, which is increasingly explored for potential value-added applications. The number of patents describing ES-based applications has increased dramatically in recent years. This review provides insight into the most recent patents published between 2015 and 2020, with focus on different engineering technologies for the screening, separation, and processing of ES. Screening technologies include detection of ES surface spots and glossiness, ES cracks, and mechanical properties, along with identification of chicken breed and enumeration of surface bacterial count. Collection and separation technologies describe separation strategies of ES from egg white (EW), egg yolk (EY), liquid egg, eggshell membrane (ESM), hatchlings, and cooked egg. Separation of ES from liquid eggs utilizes gravity, rotational forces, or air pressure. Processing of ES involves washing and sterilization along with cutting, crushing, and pulverization technologies that enable the collection of ES suitable for value-added applications. In addition, ES carving (mechanical and laser) opens up the realm of artwork and decoration. Furthermore, intact ES can be utilized for food serving. The exponential increase in innovative screening, separation, collection, and processing technologies reflects industrial interest to upscale low-value ES waste material, and is a first crucial step in the emergence of advanced technologies that exploit the biomedical, chemical, engineering, and environmental applications for ES.

Influence of electronic triage decision-support on hospital admission, left without being seen and time to physician initial assessment in the emergency department.

OBJECTIVE: To explore the impact of the implementation of eCTAS, a real-time electronic decision-support tool, on hospital admission, rate of left without being seen, and time from triage to physician initial assessment. METHODS: We conducted a cohort study using population-based administrative data from all Ontario emergency departments (EDs) that had implemented eCTAS for 9 months. We compared 6 months post-eCTAS data to the same 6 months the previous year (pre-eCTAS). We included triage encounters of adult (≥ 18 years) patients if they had one of 16 pre-specified, high-volume presenting complaints. Multivariable logistic regression and quantile regression models informed the effect of eCTAS on outcomes. RESULTS: We included data from 354,176 triage encounters from 31 EDs. There was a change in the distribution of triage scores post-eCTAS, with fewer patients classified as CTAS 2 and CTAS 3, and more patients classified as CTAS 1 and CTAS 4. Overall, hospital admission decreased post-eCTAS (adjusted OR: 0.98; 95% CI: 0.97 to 1.00), with fewer CTAS 2 and more CTAS 3 and CTAS 4 patients admitted post-eCTAS. The rate of left without being seen increased (2.8% vs. 3.0%; adjusted OR: 1.07; 95% CI: 1.03 to 1.11) post-eCTAS, while time to physician initial assessment proved similar pre and post-eCTAS. CONCLUSIONS: eCTAS implementation had little impact on admission, rate of left without being seen and time to physician initial assessment. eCTAS appears to reclassify patients from higher to lower acuity scores, resulting in higher admission rates for CTAS 3 and CTAS 4 patients. It remains unknown if this reclassification is appropriate.

RéSUMé: OBJECTIF: Étudier l'impact de la mise en œuvre de l'eCTAS, un outil électronique d'aide à la décision en temps réel, sur l'admission à l'hôpital, le taux de personnes qui ne sont pas vues et le délai entre le triage et l'évaluation initiale du médecin. LES MéTHODES: Nous avons mené une étude de cohorte en utilisant les données administratives basées sur la population de tous les services d'urgence (SU) de l'Ontario qui avaient mis en place l'eCTAS depuis 9 mois. Nous avons comparé les données de six mois après l'eCTAS aux mêmes données de six mois de l'année précédente (avant l'eCTAS). Nous avons inclus les rencontres de triage des patients adultes (≥ 18 ans) s'ils présentaient l'une des 16 plaintes pré-spécifiées à haut volume. Des modèles de régression logistique multivariable et de régression quantile ont permis d'évaluer l'effet de l'eCTAS sur les résultats. RéSULTATS: Nous avons inclus les données de 354 176 rencontres de triage provenant de 31 services d'urgence. Il y a eu un changement dans la distribution des scores de triage après l'eCTAS, avec moins de patients classés comme CTAS 2 et CTAS 3, et plus de patients classés comme CTAS 1 et CTAS 4. Dans l'ensemble, les admissions à l'hôpital ont diminué après l'eCTAS (RC ajusté: 0,98 ; 95 % IC 0,97 à 1,00), avec moins de patients CTAS 2 et plus de patients CTAS 3 et CTAS 4 admis après eCTAS. Le taux de personnes laissées sans surveillance a augmenté (2,8 % contre 3,0 % ; RC ajusté : 1,07 ; 95 % IC 1,03 à 1,11) après l'eCTAS, tandis que le délai avant l'évaluation initiale par le médecin s'est avéré similaire avant et après l'eCTAS. CONCLUSIONS: La mise en œuvre de l'eCTAS a eu peu d'impact sur l'admission, le taux de patients laissés sans consultation et le temps nécessaire à l'évaluation initiale par le médecin. L'eCTAS semble reclasser les patients des scores d'acuité supérieurs aux scores d'acuité inférieurs, ce qui entraîne des taux d'admission plus élevés pour les patients CTAS 3 et CTAS 4. On ignore encore si ce reclassement est approprié.

Exploiting Allosteric Properties of RAF and MEK Inhibitors to Target Therapy-Resistant Tumors Driven by Oncogenic BRAF Signaling.

Current clinical RAF inhibitors (RAFi) inhibit monomeric BRAF (mBRAF) but are less potent against dimeric BRAF (dBRAF). RAFi equipotent for mBRAF and dBRAF have been developed but are predicted to have lower therapeutic index. Here we identify a third class of RAFi that selectively inhibits dBRAF over mBRAF. Molecular dynamic simulations reveal restriction of the movement of the BRAF αC-helix as the basis of inhibitor selectivity. Combination of inhibitors based on their conformation selectivity (mBRAF- plus dBRAF-selective plus the most potent BRAF-MEK disruptor MEK inhibitor) promoted suppression of tumor growth in BRAFV600E therapy-resistant models. Strikingly, the triple combination showed no toxicities, whereas dBRAF-selective plus MEK inhibitor treatment caused weight loss in mice. Finally, the triple combination achieved durable response and improved clinical well-being in a patient with stage IV colorectal cancer. Thus, exploiting allosteric properties of RAF and MEK inhibitors enables the design of effective and well-tolerated therapies for BRAFV600E tumors. SIGNIFICANCE: This work identifies a new class of RAFi that are selective for dBRAF over mBRAF and determines the basis of their selectivity. A rationally designed combination of RAF and MEK inhibitors based on their conformation selectivity achieved increased efficacy and a high therapeutic index when used to target BRAFV600E tumors.See related commentary by Zhang and Bollag, p. 1620.This article is highlighted in the In This Issue feature, p. 1601.