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Muscle mass is frequently reduced in older patients experiencing injurious falls and may further reduce during hospitalization for bone fracture. In these patients, renal function may be overestimated, because it is usually calculated using serum creatinine, which is strictly related to muscle mass. We evaluated if creatinine levels change during hospitalization in older patients with fracture. We also assessed the role of cystatin C as a more appropriate marker of renal function, comparing estimated glomerular filtration rate (eGFR) according to different formulas based on creatinine and/or cystatin C levels.Patients aged 65+ years, consecutively hospitalized for fracture, were enrolled in a prospective cohort study. Creatinine and cystatin C levels were measured at baseline and in the post-operative period; eGFR was calculated using six equations based on creatinine and/or cystatin C.425 patients were enrolled (mean age 84 years, mean creatinine 0.97 mg/dL, mean cystatin C 1.53 mg/L). Creatinine levels significantly decreased after surgery (p0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was60 mL/min/1.73 mIn older fractured patients, creatinine levels decline during hospital stay and may possibly overestimate renal function, whereas cystatin C remains stable. Whether cystatin C is a more reliable marker of renal function in this specific population should be further investigated.

The objective of this study was to evaluate the effect of adding different xylanase and ?-glucanase enzyme blends to maize- and soybean meal-based diets on performance and energy metabolizability in broilers. Two experiments were carried out with broilers of the COBB 500 strain. In the first experiment, 1960 chicks were assigned to a completely randomized design with a 2 × 3 + 1 factorial arrangement, totaling seven treatments, namely, T1- Positive control (PC); T2 - Negative control 1 (NC1; PC minus 200 kcal kg-1 ME); T3 - NC1 + Blend A; T4 - NC1 + Blend B; T5 - Negative control 2 (NC2; PC minus 167 kcal kg-1 ME and 5% amino acids); T6 - NC2 + Blend A; and T7 - NC2 + Blend B. Fourteen replicates were used per treatment and 20 birds per experimental unit. The parameters evaluated at 21 and 42 days of age were weight gain (WG), feed intake (FI) and feed conversion (FC). At 42 days, production efficiency index (PEI), viability and the yields of cuts were also calculated. Birds that received diets with a reduced nutritional value showed a reduction in WG and PEI and worsened FC as compared those of PC treatment (p < 0.05). However, the birds that consumed the NC2 diet with Blend B exhibited a similar WG to those in PC group (p > 0.05) from 1 to 21 days of life. For the yield of thigh + drumstick, the factors were statistically similar (p > 0.05) to those observed in the PC birds. In the second experiment, 432 fourteen-day-old chicks were distributed in a completely randomized design with seven treatments, with eight replicates per treatment and six birds per experimental unit. The apparent metabolizable energy (AME) and nitrogen-corrected AME (AMEn) values were determined. Overall, the NC2 diet with Blend B provided the highest AME and AMEn values; however, NC1 with the same enzyme blend was the treatment which provided the lowest values. The addition of xylanase and ?-glucanase enzyme blends to maize- and soybean meal-based diets improves WG at 21 days as well as PEI in broilers; however, it does not influence the yield of cuts. Enzymes (Blend B) improve the energy metabolization of broiler diets with reduced energy and amino acid levels.

Aims The deposition of amyloid-β (Aβ) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aβ starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aβ peptides have been identified by mass spectrometry in autopsy samples from individuals with AD. Methods Selectivity of several antibodies detecting full-length, total or N-terminally truncated Aβ species has been characterized with capillary isoelectric focusing assays using a set of synthetic Aβ peptides comprising different N-termini. We further assessed the N-terminal heterogeneity of extracellular and vascular Aβ peptide deposits in the human brain by performing immunohistochemical analyses using sporadic AD cases with antibodies targeting different N-terminal residues, including the biosimilar antibodies Bapineuzumab and Crenezumab. Results While antibodies selectively recognizing Aβ1- x showed a much weaker staining of extracellular plaques and tended to accentuate cerebrovascular amyloid deposits, antibodies detecting Aβ starting with phenylalanine at position 4 of the Aβ sequence showed abundant amyloid plaque immunoreactivity in the brain parenchyma. The biosimilar antibody Bapineuzumab recognized Aβ starting at Asp-1 and demonstrated abundant immunoreactivity in AD brains. Discussion In contrast to other studied Aβ1- x -specific antibodies, Bapineuzumab displayed stronger immunoreactivity on fixed tissue samples than with sodium dodecyl sulfate-denatured samples on Western blots. This suggests conformational preferences of this antibody. The diverse composition of plaques and vascular deposits stresses the importance of understanding the roles of various Aβ variants during disease development and progression in order to generate appropriate target-developed therapies.

Objectives the association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. Aim to confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) Methods patients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. Results 571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30–60 ml/min/1.73 m2) and delirium remained significant in patients aged 75–84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. Conclusions in older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75–84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

Pomegranate (Punica granatum) is known to contain polyphenols with many potential health benefits, including anti-tumoral, anti-inflammatory, and anti-microbial properties. It has been used in popular medicine for cancer treatment, which still represents the major cause of cancer-related deaths in men worldwide. Importantly, pomegranate peels are valuable by-products of the food industry that are rich in polyphenols. Here we report a comparison between juice and peel aqueous extracts in prostate cancer DU-145 and PC-3 cell lines. Both extracts were able to inhibit the proliferation, migration and colony formation of those cells, although peel extracts presented more robust effects compared to juice. Besides, the growth-related mTOR/S6K signaling pathway presented strong inhibition after pomegranate extracts treatment. This study presents evidence that both juice and isolated peel extracts from promegate fruit have important anti-cancer effects against prostate cancer cells, modulating the mTOR/S6K signaling pathway.

SUMMARY In order to evaluate the effects of a symbiotic on 1–42-d-old broiler chicks, performance and carcass yield (CY), as well as litter concentrations of phosphorus and nitrogen were measured in a trial using 640 male chicks (Cobb 500). Birds were randomly distributed into 4 treatments with 8 replicates (pens) of 20 birds each. The treatments were different levels of the symbiotic (probiotic bacteria, exogenous enzymes, and autolyzed yeast) in the diets: 0.0, 0.5, 1.0, and 1.5 kg/t, and regression analysis using orthogonal polynomial contrasts was performed. As a challenge, it simulated conditions of commercial broilers sheds. The symbiotic provides beneficial effects for the animal's performance, especially weight gain, which increased 4.3%, in the treatment with 1.5 kg/t inclusion compared with the diet without symbiotic. Inclusion of the symbiotic in the diets provided improvements in CY and breast yield. The data suggested that the tested symbiotic is a good tool for enhancing poultry performance through nutrition.

Although beet stalks and leaves are not consumed and are usually discarded, they are an important source of bioactive flavonoids possessing antioxidant and anti-inflammatory activity. The aim of this study was to assess the effect of supplementation with beet stalks and leaves on metabolic parameters and glucose homeostasis in mice exposed to a high-fat diet. Six-week-old male Swiss mice were randomly divided into five experimental groups submitted to either standard diet (CT) or high-fat diet (HF), and HF-fed mice were subdivided into three treatment groups supplemented with oven-dehydrated beet stalks and leaves (SL), lyophilized beet stalks and leaves (Ly) or beet stalk and leaf extract (EX). Supplementation with SL promoted a mild improvement in the glucose homeostasis and decreased the protein levels of TNFα with no alterations in hepatic triglyceride content. It remains to be clarified if the enhancement in the glucose homeostasis observed in HFSL could be a consequence of improvement in pancreatic insulin secretion and/or glucose uptake from skeletal muscle and white adipose tissues.

Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. Beetroot (Beta vulgaris L.) has bioactive compounds that can inhibit the progression of different types of cancer. To analyze the antiproliferative effects of beet leaf and root extracts, we performed MTT, clonogenic survival, cell cycle analysis, Annexin/PI labeling, and western blotting. Here, we report that 10 and 100 μg/ml of root and leaf extracts decreased cell viability and potentiated rapamycin and cisplatin effects while decreased the number of large colonies, especially at 10 μg/ml (293.6 of control vs. 200.0 of leaf extract, p = .0059; 138.6 of root extract, p = .0002). After 48 hr, 100 μg/ml of both extracts led to increased sub-G1 and G0/G1 populations. In accordance, 100 μg/ml of root extract induced early apoptosis (mean = 0.64 control vs. 1.56 root; p = .048) and decreased cell size (p < .0001). Both extracts decreased phosphorylation and expression of mechanistic Target of Rapamycin (mTOR) signaling, especially by inhibiting ribosomal protein S6 (S6) phosphorylation, increasing cleaved poly(ADP-ribose) polysomerase 1 (PARP1) and Bcl-2-like protein 11 (BIM), and decreasing cyclin D1 expression, which regulates cell cycle progression. Here, we demonstrate that beetroot and leaf extracts could be an efficient strategy against cervical cancer.

Abstratc: This study aimed to examine the impact of levels of dietary supplementation with fat-soluble vitamins on the production performance and egg quality of laying hens. Three hundred Hy-Line White W-36 laying hens were evaluated from 28 to 44 weeks of age. The birds were allotted to one of six treatments in a randomized block design with 10 replicates with five birds each. Performance and egg quality parameters were evaluated in four 28-day periods. A corn and soybean meal-based basal diet was formulated so as to meet the nutritional requirements of the animals, with the exception of fatsoluble vitamins. The treatments consisted of dietary supplementation with 0%, 33.3%, 66.7%, 100.0%, 133.3% or 166.7% of fat-soluble vitamins (100% supplementation consisted of 7500 IU, 2000 IU, 10 IU and 1.8 mg of vitamins A, D3, E and K per kilogram of diet, respectively). Eggshell weight, shell thickness, shell strength, feed intake, egg weight, feed conversion per egg mass and feed conversion per dozen eggs showed a quadratic response (p≤0.05) to the treatments, whereas egg mass responded linearly. Optimal results were obtained at an average fat-soluble vitamin supplementation level of 109%, which corresponds to 8175 IU of vitamin A, 2180 IU of vitamin D3, 10.9 IU of vitamin E and 1.96 mg of vitamin K per kilogram of diet. Made available in DSpace on 2020-11-13T19:25:21Z (GMT). No. of bitstreams: 1 final9539.pdf: 635933 bytes, checksum: d767db846d09362fbffddc650d59f720 (MD5) Previous issue date: 2020

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly found in bone and joint infections, including septic arthritis. S. aureus virulence and the frailty of affected patients can cause several complications, a prompt and specific antibiotic treatment can positively affect the outcome of patients. We carried out an in-depth genomic characterization by Illumina whole genome sequencing and bioinformatics of two biofilm-producing M1 and M2 ST398 MSSA causing septic knee arthritis not-responding to antimicrobial therapy. The strains were characterized for antibiotic resistance, biofilm and adhesive properties as well as genomics, single nucleotide polymorphism phylogeny, resistomics and virulomics. Our results showed that M1 and M2 MSSA were ST398-t1451-agrI-Cap5, susceptible to cefoxitin and resistant to erythromycin and clindamycin, traits consistent with the lack of the SCCmec-locus and the presence of the sole blaZ and ermT. Furthermore, M1 and M2 were biofilm-producing and largely potentially adhesive strains, as indicated by the adhesion gene profile. Our data characterized a new human-adapted ST398 MSSA lineage, representing a “fusion” between the human-animal independent ST398 and the Livestock Associated (LA) ST398 lineages, forming biofilm and genomically predicted high adhesive, characterized by different genomic adaptation conferring a great ability to adhere to the host’s extracellular matrix causing septic knee arthritis.

A population of more than six million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical β and γ-secretase inhibition. We found that T21 organoids secrete increased proportions of Aβ-preventing (Aβ1–19) and Aβ-degradation products (Aβ1–20 and Aβ1–34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.

Cardiovascular complications in patients undergoing non-cardiac surgery are associated with longer hospital stays and higher in-hospital mortality. The aim of this study was to assess the incidence of in-hospital myocardial infarction and/or myocardial injury in patients undergoing hip fracture surgery and their association with mortality. Moreover, we evaluated the prognostic value of troponin increase stratified on the basis of peak troponin value. The electronic records of 1970 consecutive hip fracture patients were reviewed. Patients &lt, 70 years, those with myocardial infarction &lt, 30 days, and those with sepsis or active cancer were excluded from the study. Troponin and ECG were obtained at admission and then at 12, 24, and 48 h after surgery. Echocardiography was made before and within 48 h after surgery. Myocardial injury was defined by peak troponin I levels &gt, 99th percentile. A total of 1854 patients were included. An elevated troponin concentration was observed in 754 (40.7%) patients in the study population. Evidence of myocardial ischemia, fulfilling diagnosis of myocardial infarction, was found in 433 (57%). ECG and echo abnormalities were more frequent in patients with higher troponin values, however, mortality did not differ between patients with and without evidence of ischemia. Peak troponin was between 0.1 and 1 &micro, g/L in 593 (30.3%). A total of 191 (10 %) had peak troponin I &ge, 1 &micro, g/L, and 98 died in hospital (5%). Mortality was significantly higher in both groups with troponin increase (HR = 1.37, 95% CI 1.1&ndash, 1.7, p &lt, 0.001 for peak troponin I between 0.1 and 1 &micro, g/L, HR = 2.28, 95% CI 1.72&ndash, 3.02, p &lt, 0.0001 for peak troponin &ge, g/L) in comparison to patients without myocardial injury. Male gender, history of coronary heart disease, heart failure, and chronic kidney disease were also associated with in-hospital mortality. Myocardial injury/infarction is associated with increased mortality after hip fracture surgery. Elevated troponin values, but not ischemic changes, are related to early worse outcome.

Impaired clearance in the Alzheimer's Disease (AD) brain is key in the formation of Aβ parenchymal plaques and cerebrovascular deposits known as cerebral amyloid angiopathy (CAA), present in >80% of AD patients and ~50% of non‐AD elderly subjects. Aβ deposits are highly heterogeneous, containing multiple fragments mostly derived from catabolism of Aβ40/Aβ42, which exhibit dissimilar aggregation properties. Remarkably, the role of these physiologically relevant Aβ species in cerebrovascular injury and their impact in vascular pathology is unknown. We sought to understand how heterogeneous Aβ species affect cerebral endothelial health and assess whether their diverse effects are associated with the peptides aggregation propensities. We analyzed cerebral microvascular endothelial cell (CMEC) viability, blood‐brain barrier (BBB) permeability, and angiogenesis, all relevant aspects of brain microvascular dysfunction. We found that Aβ peptides and fragments exerted differential effects on cerebrovascular pathology. Peptides forming mostly oligomeric structures induced CMEC apoptosis, whereas fibrillar aggregates increased BBB permeability without apoptotic effects. Interestingly, all Aβ species tested inhibited angiogenesis in vitro. These data link the biological effects of the heterogeneous Aβ peptides to their primary structure and aggregation, strongly suggesting that the composition of amyloid deposits influences clinical aspects of the AD vascular pathology. As the presence of predominant oligomeric structures in proximity of the vessel walls may lead to CMEC death and induction of microhemorrhages, fibrillar amyloid is likely responsible for increased BBB permeability and associated neurovascular dysfunction. These results have the potential to unveil more specific therapeutic targets and clarify the multifactorial nature of AD., This study demonstrates that full length Aβ peptides, truncated Aβ fragments, and vasculotropic Aβ variants, differentially impact microvascular endothelial cell function, in relation to their aggregation properties. Understanding these effects on separate but interconnected cerebrovascular degeneration pathways, such as BBB permeability, EC apoptosis and angiogenesis, will provide new insights into the pathology and different clinical subtypes of AD and vascular dementia.

Acai is one of the leading Brazilian Amazon fruits, which pulp is consumed throughout the country and exported to several others. Acai by-product represents 80–90% berry mass. In order to reuse the by-product, pressurized liquid extraction (PLE) was applied. Solvent composition and temperature were studied through their effect on the global extraction, total phenolic, reducing sugars yields, and antioxidant capacity. High temperature (115 oC) and ethanol+water (75 wt%) favored obtaining antioxidant extracts. These PLE conditions were kinetically studied and economically evaluated. The end of the first theoretical extraction period (tCER) resulted in the extracts’ minimum cost of manufacturing (COM). Regardless of the extraction time, scale-up reduced the COM, advising the process at large scales. A sensitivity study was carried out considering different extract selling prices as scenarios. All the estimated selling prices showed encouraging economic indexes. PLE proved to be technically and economically feasible to obtain acai by-product extracts with confirmed antioxidant capacity.

Extensive parenchymal and vascular Aβ deposits are pathological hallmarks of Alzheimer's disease (AD). Besides classic full-length peptides, biochemical analyses of brain deposits have revealed high degree of Aβ heterogeneity likely resulting from the action of multiple proteolytic enzymes. In spite of the numerous studies focusing in Aβ, the relevance of N- and C-terminal truncated species for AD pathogenesis remains largely understudied. In the present work, using novel antibodies specifically recognizing Aβ species N-terminally truncated at position 4 or C-terminally truncated at position 34, we provide a clear assessment of the differential topographic localization of these species in AD brains and transgenic models. Based on their distinct solubility, brain N- and C-terminal truncated species were extracted by differential fractionation and identified via immunoprecipitation coupled to mass spectrometry analysis. Biochemical/biophysical studies with synthetic homologues further confirmed the different solubility properties and contrasting fibrillogenic characteristics of the truncated species composing the brain Aβ peptidome. Aβ C-terminal degradation leads to the production of more soluble fragments likely to be more easily eliminated from the brain. On the contrary, N-terminal truncation at position 4 favors the formation of poorly soluble, aggregation prone peptides with high amyloidogenic propensity and the potential to exacerbate the fibrillar deposits, self-perpetuating the amyloidogenic loop. Detailed assessment of the molecular diversity of Aβ species composing interstitial fluid and amyloid deposits at different disease stages, as well as the evaluation of the truncation profile during various pharmacologic approaches will provide a comprehensive understanding of the still undefined contribution of Aβ truncations to the disease pathogenesis and their potential as novel therapeutic targets.

Familial British and Danish dementias (FBD and FDD) share striking neuropathological similarities with Alzheimer's disease (AD), including intraneuronal neurofibrillary tangles as well as parenchymal and vascular amyloid deposits. Multiple amyloid associated proteins with still controversial role in amyloidogenesis colocalize with the structurally different amyloid peptides ABri in FBD, ADan in FDD, and Aβ in AD. Genetic variants and plasma levels of one of these associated proteins, clusterin, have been identified as risk factors for AD. Clusterin is known to bind soluble Aβ in biological fluids, facilitate its brain clearance, and prevent its aggregation. The current work identifies clusterin as the major ABri- and ADan-binding protein and provides insight into the biochemical mechanisms leading to the association of clusterin with ABri and ADan deposits. Mirroring findings in AD, the studies corroborate clusterin co-localization with cerebral parenchymal and vascular amyloid deposits in both disorders. Ligand affinity chromatography with downstream Western blot and amino acid sequence analyses unequivocally identified clusterin as the major ABri- and ADan-binding plasma protein. ELISA highlighted a specific saturable binding of clusterin to ABri and ADan with low nanomolar Kd values within the same range as those previously demonstrated for the clusterin-Aβ interaction. Consistent with its chaperone activity, thioflavin T binding assays clearly showed a modulatory effect of clusterin on ABri and ADan aggregation/fibrillization properties. Our findings, together with the known multifunctional activity of clusterin and its modulatory activity on the complex cellular pathways leading to oxidative stress, mitochondrial dysfunction, and the induction of cell death mechanisms - all known pathogenic features of these protein folding disorders - suggests the likelihood of a more complex role and a translational potential for the apolipoprotein in the amelioration/prevention of these pathogenic mechanisms. This work was supported by grants from the National Institutes of Health NS051715 (to AR) and AG030539, AG051266, AG059695, and AG065651 (to JG) and from CIBERNED and the Spanish Ministry of Science (SAF2016-78603-R and PID2019-110401RB-I00) and Institutional grants from the Queen Sofia Foundation, CIEN Foundation and the Carlos III Institutes of Health (to MC). TL is supported by an Alzheimer's Research UK senior fellowship. TR is supported by a grant from the Karin & Sten Mortstedt CBD Solutions AB, Stockholm, Sweden and by the National Institute for Health Research (NIHR) Queen Square Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL). The views expressed are those of the authors and not necessarily those of the NIH, NHS, the NIHR or the Department of Health. Sí

The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF) in lung fibroblasts derived from COX-2-/- but not wild-type (WT) or COX-1-/- mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2-/- fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2-/- was "prostaglandin-independent." GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2-/- cells. Furthermore, COX-2-/- fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen) analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

Feed withdrawal and transport commonly occur together in pigs. Objectives of this study were to determine if these preslaughter stressors, feed withdrawal and transportation, affect the levels of , stress hormone concentrations, and immune functions in infected market pigs. A 2 × 2 factorial analysis of a randomized complete block design with feed withdrawal and transport as fixed effects was used. Sixty market-weight pigs were individually inoculated with serovar Typhimurium. The experiment was replicated 3 times (blocking factor) with 20 pigs per replicate. Three days after inoculation, the pigs were randomly assigned to 1 of 4 treatments (5 pigs per treatment in each/replicate), including 1) control (Control; or no stress), 2) feed withdrawal for 12 h (FW), 3) transportation for 2 h (T), and 4) feed withdrawal for 12 h followed by transportation for 2 h (FWT). Feed withdrawal by itself or followed by transportation caused an increase of levels in ileal contents ( 0.10). Cortisol increased in pigs from all 3 stress treatments ( 0.03). Each granulocyte percentage (neutrophil, eosinophils, and basophils) increased ( 0.05) by feed withdrawal with transport. Lymphocytes were suppressed ( < 0.05) by all stressors, and the greatest suppression occurred when pigs were transported (T and FWT). However, monocytes were suppressed ( < 0.05) compared with Controls only by FWT. Expression of IL-1 (produced by monocytes/macrophages) from the spleen cells increased ( < 0.05) with FW compared with Controls, whereas its receptor antagonist was suppressed by FWT ( < 0.05). It is concluded that some typical preslaughter practices, such as feed withdrawal and transportation, lead to greater intestinal levels and gut-associated lymphoid tissue markers of inflammation in market pigs and, consequently, to an increased food safety risk.

Stress is a biological adaptive response to restore homeostasis, and occurs in every animal production system, due to the multitude of stressors present in every farm. Heat stress is one of the most common environmental challenges to poultry worldwide. It has been extensively demonstrated that heat stress negatively impacts the health, welfare, and productivity of broilers and laying hens. However, basic mechanisms associated with the reported effects of heat stress are still not fully understood. The adaptive response of poultry to a heat stress situation is complex and intricate in nature, and it includes effects on the intestinal tract. This review offers an objective overview of the scientific evidence available on the effects of the heat stress response on different facets of the intestinal tract of poultry, including its physiology, integrity, immunology, and microbiota. Although a lot of knowledge has been generated, many gaps persist. The development of standardized models is crucial to be able to better compare and extrapolate results. By better understanding how the intestinal tract is affected in birds subjected to heat stress conditions, more targeted interventions can be developed and applied.

Pomegranate (Punica granatum L.) has been used in traditional herbal medicine by several cultures as an anti‐inflammatory, antioxidant, antihyperglycemic, and for treatment and prevention of cancer and other diseases. Different parts of the fruit, extraction methods, and solvents can define the chemical profile of the obtained extracts and their biological activities. This study aimed to characterize the chemical profile of peel extracts collected using different extraction solvents and their biological effects on the cell cycle and apoptosis of THP‐1 leukemic cells. Aqueous extract presented the highest content of punicalagins (α pun = 562.26 ± 47.14 mg/L and β pun = 1,251.13 ± 22.21 mg/L) and the lowest content of ellagic acid (66.38 ± 0.21 mg/L), and it promoted a significant impairment of the cell cycle S phase. In fact, punicalagin‐enriched fraction, but not an ellagic acid‐enriched fraction, caused an S phase cell cycle arrest. All extracts increased the number of apoptotic cells. Punicalagin‐enriched fraction increased the percentage of cells with fragmented DNA, which was intensified by ellagic acid combination. The treatment combining punicalagin and ellagic acid fractions increased the apoptotic cleaved PARP1 protein and reduced the activation of the growth‐related mTOR pathway. Thus, these results evidence that solvent choice is critical for the phenolic compounds profile of pomegranate peel extracts and their biological activities., The main aim of this study was to assess and compare the differences in the chemical profile of pomegranate peel extracts obtained using different extraction solvents and how does it affect their biological properties.

Beetroot is an herb used worldwide as a food product, raw material for food industry, ethanol production and source of food coloring. Beet leaves are an unconventional food with antioxidant properties, which might neutralize reactive oxygen species (ROS) induced by oxidized Low-Density Lipoprotein (LDL) present in dyslipidemias. This study aimed to elucidate the effects of beet leaves on the suppression of LDL oxidative processes. Beet leaves extract was produced, characterized, and tested for its antioxidant capacity using endothelial cells in vitro. A model of human umbilical vein endothelial cells was used in various tests, including viability assay, molecular analysis of antioxidant genes, ROS labeling, and macrophage adhesion assay. The extract improved the antioxidative protection of endothelial cells against different agents including oxidized LDL-cholesterol and H2 O2 . It acted on ROS directly due to its high content of natural antioxidants, but also due to the activation and improvement of cellular defenses such as Superoxide dismutase 1, Superoxide dismutase 2, and catalase. The inhibition of LDL-mediated oxidative effects on endothelial cells may turn this unconventional food a functional food with great potential for phytotherapy of atherosclerosis as an adjuvant for medicinal treatments.

Extracts rich in phenolic compounds and anthocyanins from industrial residue of jucara (Euterpe edulis Mart.) were obtained using different high pressure extraction processes. Pressurized Liquid Extraction (PLE) was evaluated at 10 MPa and 40, 60 and 80 °C using ethanol, water, acidified mixture of ethanol + water and acidified water as solvents. The best solvent in PLE was selected as cosolvent for supercritical fluid extraction (SFE) with CO2. Among the PLE extracts, the highest antioxidant activity and concentration of phenolics were obtained with the acidified mixture of ethanol + water at 80 °C and the highest anthocyanin content was achieved with acidified water at 40 °C. Based on the PLE results, a two-stage sequential extraction strategy was adopted, producing an extract rich in anthocyanins and another rich in heat resistant phenolic compounds. The selected cosolvent (acidified mixture ethanol + water) for SFE improved significantly the anthocyanin content. Four anthocyanins were identified and quantified by UPLC.

The aim of this study was to evaluate dietary crude protein (CP) levels for laying hens. 180 Hy-Line W-36 laying hens, with ages ranging from 27 to 43 weeks old, were distributed according to a randomized block design into three treatments with 10 replicates of six birds per cage. The dietary nutritional levels were adequate, except for CP. The treatments were 152, 172, and 182 g/kg. The following parameters were evaluated: feed intake (FI, g/day), egg production (EP, g/kg), egg weight (EW, g), egg mass (EM, g/day), feed conversion ratio (FCR, kg/kg and kg/dozen), yolk (g/kg of EW), eggshell (g/kg of EW), and albumen (g/kg of EW). Feed intake was not influenced by dietary CP levels (p>0.05). Egg weight, EM, FCR (kg/kg), and albumen were not influenced (p>0.05) by the treatments. Birds fed on diets with 172 g/kg CP showed an improvement (p

The aim of this study was to evaluate the effects of essential-to-total nitrogen (eN-to-tN) ratios supplemented with nonessential amino acids (NEAAs) in low-protein diets on the performance, nitrogen retention and blood parameters of broiler chickens from 8 day to 21 day posthatch. A total of 300 male Cobb® 500 chickens were weighed and allocated to one of six dietary treatments with 10 replicate pens in a completely randomized experimental design. The treatments were: T1, a control with 222.5 g/kg crude protein (CP) and a 47 % eN-to-tN ratio; T2, 190 g/kg CP and a 56 % eN-to-tN ratio; T3, 190 g/kg CP +12.01 g/kg of a NEAA mixture and a 53 % eN-to-tN ratio; T4, 190 g/kg CP +25.16 g/kg of an NEAA mixture and a 50 % eN-to-tN ratio; T5, 190 g/kg CP +39.99 g/kg of an NEAA mixture and a 47 % eN-to-tN ratio; and T6, 190 g/kg CP +56.83 g/kg of an NEAA mixture and a 44 % eN-to-tN ratio. The NEAA mixture consisted of alanine, glycine and glutamic acid (20:20:60). Performance was measured at 21 day. From 14 day to 21 day, excreta were collected to calculate nitrogen utilization. At 21 day, blood was collected from the wing vein to quantify uric acid, total protein, albumin and globulin and to evaluate nitrogen utilization. The data were analyzed using a Dunnett test, and the growth performance and blood parameters of the five progressive treatment levels were assessed using the linear response plateau (LRP) and quadratic broken line (QBL) models to estimate requirements. Birds fed diets with a 56 % eN-to-tN ratio exhibited a lower final body weight (FBW) and feed conversion ratio (FCR) than birds fed the control diet, whereas birds fed a diet with a 53 % eN-to-tN ratio only had a lower FCR. The LRP for FBW, body weight gain (BWG), feed intake (FI) and FCR showed an Xplat very close to a 50 % eN-to-tN ratio. Despite their good performance, animals fed diets with 47 % and 44 % eN-to-tN ratios were less efficient in terms of nitrogen utilization than birds fed a diet with a 50 % eN-to-tN. Thus, to maintain broiler performance and efficient nitrogen metabolism, low CP diets should possess an eN-to-tN ratio of 50 % or less.

This project proposed the study of the best means of extracting bioactive compounds present in the apple peel, from the industrial residues, and its application for the elaboration of cookies with functional properties. To this end, a dry extract of apple peel and industrial by-product was made by freeze-drying to replace wheat flour of the traditional formulation in different concentrations (2.5%, 5%, 7.5% 10%), analyzing the thermal stability of the compounds by comparing the raw and roasted mass. The extracts obtained were evaluated for total phenol content using the Folin-Ciocalteu (FT) reagent method, the antioxidant activity (AC) by the FRAP and ABTS method and the Liquid Chromatography (HPLC) analysis. The results showed that Extract of the by-product presented a higher concentration of total phenolics and antioxidant activity than the flour from the apple peel, as well as the stability of the compounds after cooking.

In this study it is proposed the introduction of an expansion gas in high pressure water to maximize the cavitation caused by the application of ultrasound to improve the extraction of phenolic compounds from pomegranate peel. Different combinations of ultrasound power (US-Pwr), expansion gas initial pressure (N2-Pi), system pressure (SP) and particle size of sample were evaluated using water as solvent. The use of US-Pwr and N2-Pi individually or combined improved the extraction process proving higher yields. SP was an important parameter affecting extraction yield, showing an inverse relation between its increase and extraction yield. Although higher yields were produced with samples with smaller particles, the combination of ultrasound and expansion gas had a positive effect on the process independently of particle size, promoting an increase of 20-26% in yield. These results suggest an enormous potential to be explored with the introduction of an expansion gas in pressurized liquids in processes assisted by ultrasound for the extraction of phenolic compounds from natural products using green solvents.

The intestinal gene expression of RelA/p65 (NF-κB), insulin growth factor 1 (IGF-1), glucose transporter 2 (GLUT2), and Na+/dependent glucose transporter 1 (SGLT1) were evaluated in response to benzoic acid, yeast culture, L-glutamine, and oregano essential oil, using an ex vivo model. Six piglets weighing approximately 20 kg each were sacrificed, and their jejunum was collected and segmented into five 2-cm explants. Each explant was immersed in cell culture medium according to one of the following treatments: control (without additive), 0.5% benzoic acid, 1% yeast culture, 1% L-glutamine, and 0.015% oregano oil. Gene expression was evaluated using RT-PCR. Yeast culture up-regulated the gene expression of RelA/p65, IGF-1, GLUT2, and SGLT1 in comparison with control. In addition, jejunal exposure to L-glutamine and oregano oil increased mRNA levels of GLUT2 compared with the control treatment. Exposure to oregano oil increased intestinal SGLT1 gene expression, while benzoic acid reduced SGLT1 expression compared with the control. Feed additives can differently modulate the gene expression of immune response, gut development, and glucose absorption in jejunal explants. These findings can contribute for a better understanding of the trophic action of these feed additives into the diets to optimize animal performance.

International audience; Mitochondrial dysfunction has been recognized as an early event in Alzheimer's disease (AD) pathology, preceding and inducing neurodegeneration and memory loss. The presence of cytochrome c (CytC) released from the mitochondria into the cytoplasm is often detected after acute or chronic neurodegenerative insults, including AD. The carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) was identified among a library of drugs as an inhibitor of CytC release and proved to be neuroprotective in Huntington's disease and stroke models. Here, using neuronal and glial cell cultures, in addition to an acute model of amyloid beta (Aβ) toxicity, which replicates by intra-hippocampal injection the consequences of interstitial and cellular accumulation of Aβ, we analyzed the effects of MTZ on neuronal and glial degeneration induced by the Alzheimer's amyloid. MTZ prevented DNA fragmentation, CytC release and activation of caspase 9 and caspase 3 induced by Aβ in neuronal and glial cells in culture through the inhibition of mitochondrial hydrogen peroxide production. Moreover, intraperitoneal administration of MTZ prevented neurodegeneration induced by intra-hippocampal Aβ injection in the mouse brain and was effective at reducing caspase 3 activation in neurons and microglia in the area surrounding the injection site. Our results, delineating the molecular mechanism of action of MTZ against Aβ-mediated mitochondrial dysfunction and caspase activation, and demonstrating its efficiency in a model of acute amyloid-mediated toxicity, provide the first combined in vitro and in vivo evidence supporting the potential of a new therapy employing FDA-approved CAIs in AD.

This study aimed at evaluating four dietary L-Glutamine (L-Gln) or L-Gln plus L-Glutamate (L-Glu) supplementation programs on the performance, breast yield, and uniformity of broilers. A total of 2,112 one-d-old male Cobb 500(r) broilers were distributed according to a randomized block design in a 2 × 4 factorial arrangement (L-Gln or L-Gln plus L-Glu × 4 supplementation programs), totaling eight treatments with 12 replicates of 22 broilers each. The supplementation programs consisted of the dietary inclusion or not of 0.4% of L-Gln or L-Gln plus L-Glu for four different periods: 0 days (negative control), 9d, 21d, and 42d. Feed intake (FI, g), body weight gain (BWG, g), feed conversion ratio (FCR, kg/kg), coefficient of variation of body weight (CV, %), body weight uniformity (UNIF, %), breast weight (BW, g), breast yield (BY, %), coefficient of variation of breast weight (CVB), breast uniformity (UNIFB), coefficient of variation of breast yield (CVBY), and breast yield uniformity (UNIFBY) were evaluated. Birds fed the diets treatments supplemented with L-Gln or L-Gln plus L-Glu for 9d presented 3% higher BWG (p

Myocardial infarction after hip fracture but before surgical repair is associated with a 30-day mortality as high as 30 % at 1 month. In Florence, since 2011, hip fractures are referred to a multidisciplinary hip fracture team including internal medicine specialists, anesthesiologists, and orthopaedic surgeons. The aim of the present investigation was to evaluate the clinical characteristics of patients with hip fracture who had at hospital admission a significant increase of troponin (>10 times reference levels), the diagnostic and therapeutic strategies adopted, and overall 1-year survival. Protocol at admission included careful clinical evaluation (including bedside echocardiography) in order to stratify surgical risk and schedule surgery and anaesthesiology strategy. 21/1025 patients had preoperative significant troponin increase. In sixteen patients, a diagnosis of NSTEMI was made, five presented with ST elevation. In five patients with NSTEMI considered at very high surgical risk (ASA ≥ 3, severe cognitive and functional impairment), surgery was not performed. None survived at 1 year. Hip surgery was performed in the other 11. Four underwent coronary revascularization after hip surgery. In this group, 1-year survival was 80 %. Four of five ST elevation patients fulfilled criteria for stress cardiomyopathy confirmed by angiography. Hip surgery was performed, and the patients are alive at 1-year follow-up. Close to 2 % of patients with hip fracture are found to have a significant troponin increase before surgery. Three out of four have an NSTEMI diagnosis. In patients undergoing hip surgery, survival at 1 year is close to 80 %. In patients with ST elevation at admission, stress cardiomyopathy should be considered in the differential diagnosis. This clinical condition is associated with a favourable prognosis after hip surgery.

Extracting volatile compounds using supercritical carbon dioxide (scCO 2 ) is one of the most interesting applications of supercritical technology because of the high solubility of these substances in CO 2 . Supercritical carbon dioxide extraction (SFE) has been applied for obtaining extracts from several vegetable matrices, including turmeric ( Curcuma longa L.), due to its valuable volatile oil. However, a techno-economic evaluation of turmeric oil and ar-turmerone extraction has not yet been performed. Therefore, the effects of temperature, pressure and process time on the extract yield, relative ar-turmerone yield and manufacturing cost were evaluated in this work. Turmeric rhizomes were ground, sieved and placed in contact with scCO 2 flowing at 8.4 × 10 −3 kg/min in a laboratory scale SFE unit. Major compounds in the extracts were identified and quantified by gas chromatography. The manufacturing cost (COM) of the extracts was estimated using a model cost developed in the simulator SuperPro Designer 8.5 ® . Using SFE led to high yields of extract and ar-turmerone. Fast extraction combined with relatively low solvent consumption were observed. Yields of 6.4% and 1.02% of extract and ar-turmerone, respectively, were obtained at 333 K and 25 MPa for a solvent mass to feed mass ratio of 1.31. For these conditions, the lowest manufacturing cost (COM = US$ 178.8/kg extract) was estimated for a unit containing two 0.005-m 3 extractors.

O experimento foi realizado no Departamento de Zootecnia da Universidade Federal de Viçosa a fim de avaliar o efeito da adição de probióticos sobre a digestibilidade ileal em dietas de frangos de corte. Foram utilizados 400 pintos de corte machos, Cobb 500, de 21 a 31 dias de idade, distribuídos em um delineamento experimental em blocos casualizados, contendo 10 tratamentos em esquema fatorial 5 x 2 (Sem probiótico, com antibiótico e com cepas e concentrações diferentes de Bacillus subtilis) e dois níveis de energia metabolizável: Normal e -100 kcal), com 8 repetições de 5 aves por unidade experimental. Nas três primeiras semanas de vida, com o objetivo de aumentar o desafio sanitário as aves receberam, duas vezes por semana, uma solução de cama reutilizada e água na proporção de 25 g/l durante 8 horas. A adição dos promotores de crescimento acarretou incremento na digestibilidade ileal da matéria seca em média de 6,79 % (67,56 % vs 63,26 %) e aumento da digestibilidade da proteína bruta em 3,64 % (79,45 % vs 76,66 %) sobre a dieta sem o aditivo. A adição de probiótico a base de Bacillus subtilis ou do antibiótico bacitracina metileno dissalicilato nas dietas de frangos de corte em condições de desafio sanitário é eficiente na melhora dos coeficientes de digestibilidade da materia seca e da proteína bruta. The experiment was conducted at Department of Animal Science, Federal University of Viçosa to evaluate the effect of adding probiotics on ileal digestibility in diets for broilers. Four hundred male chicks Cobb 500, between 21-31d of age, were distributed in a randomized complete block design with 10 treatments in a factorial 5 x 2 (No probiotic, with antibiotic and with different strains and concentrations of Bacillus subtilis; and two levels of metabolizable energy: Normal and -100 kcal), with 8 replicates of 5 birds each. In the first three weeks of life, with the goal of increasing the health challenge of the birds received twice a week, a solution of reused litter and water in the ratio of 25 g/l for 8 hours. The addition of growth promoters resulted in increased ileal digestibility of dry matter averaged 6.79 % (67.56 % vs 63.26 %) and increased digestibility of crude protein in 3.64 % (79.45 % vs 76.66 %) on diet without the additive. The addition of probiotics based on Bacillus subtilis or antibiotic bacitracin methylene or dissalicilato in the diets of broilers in terms of health challenge is efficient to improve the digestibility of dry matter and crude protein.

The combination of ultrasound and pressurized liquid extraction (UAPLE) was evaluated for the extraction of phenolic compounds from pomegranate peels (Punica granatum L.). The influence of several variables of the process on extraction yield, including solvent type (water, ethanol + water 30, 50 and 70% v:v), temperature (50–100 °C), ultrasound power (0–800 W at the generator, or 0–38.5 W at the tip of the probe), mean particle size (0.68 and 1.05 mm), and number of cycles (1–5), were analyzed according to the yield of 20 different phenolic compounds. The most suitable temperatures for the extraction of phenolic compounds using water were from 70 to 80 °C. In general, 100 °C was not adequate since the lowest extraction yields were observed. Results suggested that ultrasound had a greater impact on extraction yields using large particles and that intermediate ultrasound power (480–640 W at the generator, or 23.1–30.8 W at the tip of the probe) produced the best results. Using small particles (0.68 mm) or large particles (1.05 mm), extraction with ultrasound was 1 cycle faster. Ultrasound may have offset the negative effect of the use of large particles, however, did not increase the yield of phenolic compounds in any of the cases studied after five cycles. Additionally, the continuous clogging problems observed with small particles were avoided with the use of large particles, which combined with ultrasound allowed consistent operation with good intra and inter-day reproducibility (>95%). Using samples with large particle size, the best extraction conditions were achieved with water extraction solvent, 70 °C extraction temperature, ultrasound power at 480 W, and 3 cycles, yielding 61.72 ± 7.70 mg/g. UAPLE demonstrated to be a clean, efficient and a green alternative for the extraction of phenolic compounds from pomegranate peels. These findings indicate that UAPLE has a great potential to improve the extraction of bioactive compounds from natural products.

Stress is intrinsically part of animal welfare, and inevitably occurs in all farm animals. Although the link between stress in farm animals and food safety is generally accepted, the understanding of how it occurs is limited. Substantial evidence exists supporting a bidirectional neuroendocrine–immune axis, which has been the basis for understanding how stress affects the occurrence of pathogens. However, the emerging field of microbial endocrinology has also revealed how stress mediators exert direct effects on bacteria in the gastrointestinal tract. Additionally, many studies demonstrate how different stressors lead to increased food safety risk through increased infection and shedding of foodborne pathogens. It is concluded that stress in farm animals can significantly affect food safety risk through different pathways. However, while there is evidence linking stress to pathogen carriage and shedding, gaps in knowledge exist and warrant further study so that risk factors can be mitigated and interventions applied, reducing risk to consumers.

The aim of this study was to assess the microbiological profile of leafy vegetables from organic and conventional farming (n=70). The microbiological parameters analyzed consisted of aerobic mesophilic bacteria, yeasts and molds, coliforms at 30 and 45°C, and Salmonella ssp. A biochemical identification of the Enterobacteriaceae species was carried out. Some Enterobacteriaceae species were identified in the produce from both farming systems and Hafnia alvei was the most widespread specie observed. Salmonella spp. was not detected in the samples analyzed. The microbial counts for indicator microorganisms were, in general, higher for conventional leaves when compared to those produced by organic farming.

Contains fulltext : 88727.pdf (Publisher’s version ) (Open Access) Heterozygous mutations in the TP63 transcription factor underlie the molecular basis of several similar autosomal dominant ectodermal dysplasia (ED) syndromes. Here we provide a novel cellular model derived from embryonic stem (ES) cells that recapitulates in vitro the main steps of embryonic skin development. We show that ES cells carrying AEC or EEC mutations are unable to differentiate into the epidermal fate. Comparative transcriptome analysis strongly reveals an embryonic epidermal signature and suggests that mutations in the SAM domain (AEC) provide activating properties while mutations in the DBD domain (EEC) induce strong inhibitory capabilities. Our model uncovers the effect of relevant ED mutations that otherwise are difficult to evaluate on the ectodermal embryonic stage, an embryonic event critical for proper skin formation.

Resumo Objetivou-se determinar a exigência de metionina + cistina total para frangas na fase inicial e verificar seu efeito sobre a fase de postura. Na primeira fase experimental, 720 aves (50% Lohmann LSL e 50% Lohmann Brown) com uma semana de idade foram distribuídas em delineamento experimental inteiramente casualizado, em esquema fatorial 5 x 2 (níveis de met + cis e linhagens), com quatro repetições e 18 aves por repetição. Os níveis de met + cis total estudados foram 0,536; 0,616; 0,696; 0,776; e 0,856 %. Ao atingirem 22 semanas de idade, iniciou-se a segunda fase experimental, sendo utilizadas 240 aves (50% Lohmann LSL e 50% Lohmann Brown) provenientes da primeira fase experimental. A ração fornecida às aves nesta fase foi igual para todos os tratamentos. Na fase de produção avaliaram-se os efeitos residuais das dietas fornecidas no período inicial sobre os parâmetros produtivos. As exigências de metionina + cistina recomendadas para aves leves e semipesadas, no período de 1 a 6 semanas de idade, são de 0,778% de met + cis total (correspondendo a 0,700% de met + cis digestível) e 0,739% de met + cis total (correspondendo a 0,665% de met + cis digestível), respectivamente. Abstract An experiment was carried out to evaluate the requirement of methionine +cystine for growing pullets at starter phase (1 to 6 weeks old) and its effect on the laying phase. In the first experiment, 720 birds (50% Lohmann LSL and 50% Lohmann Brown) at one week of age were distributed on a completely randomized design, 5 x 2 factorial arrangement (levels of met + cys and strain), with four replications and 18 birds each. The levels of total methionine + cystine studied were 0.536; 0.616; 0.696; 0.776; and 0.856 %. At 22 weeks of age, 240 birds were used for the second experimental phase. The diets given to birds at this phase was the same for all the treatments. In the production phase, the residual effects of the experimental diets provided during the initial phase on the production parameters were evaluated. The level of methionine + cystine recommended for white-egg and brown-egg pullets in the period from 1 to 6 weeks of age are 0.778 % of total methionine + cystine (0.700% met + cis digestible) and 0.739% of total methionine + cystine (0.665% of digestible methionine + cystine), respectively.

Considering that Val may potentially be a limiting amino acid for laying hens, an experiment was carried out to determine the ideal digestible Val-to-Lys ratio in the diets of 42- to 54-wk-old brown layers. Literature reports are divergent, with ratios varying between 86 and 102%, which suggests that further research is needed. Five different digestible Val-to-Lys ratios were evaluated: 84 (0.555% digestible Val), 88, 92, 96, and 100%. Feed intake (g/hen per day), egg production (%), egg weight (g), egg mass (g), FCR (kg/dozen and g/g), egg quality (yolk, eggshell, and albumen %), and egg weight (g) were evaluated. Egg weight, egg internal quality, and weight gain were not influenced by the different dietary digestible Val-to-Lys ratios. The evaluated ratios linearly affected feed intake and had a quadratic effect on egg production, egg mass, and FCR (kg/dozen and g/g). Based on the evaluated parameters, the ideal digestible Val-to-Lys ratio is 92%, corresponding to 0.607% digestible Val or 567 mg/hen per day of digestible Val.

Pressurized liquid extraction (PLE) of curcuminoids from deflavored turmeric rhizomes was optimized. The rhizomes were initially deflavored by extraction with supercritical CO2. Immediately after SFE, PLE process was performed using ethanol as the solvent and a static extraction time of 20 min, and the independent variables were the temperature (333–353 K) and pressure (10–35 MPa). The results indicate that the optimum extraction temperature and pressure were 333 K and 10 MPa, respectively. PLE required three and six times less extraction time than low-pressure solvent extraction and Soxhlet extraction, respectively, to produce similar extraction yields. The cost of manufacturing (COM) decreased from US$ 94.92 kg−1 to US$ 88.26 kg−1 when the capacity of the two-extractor system increased from 0.05 m3 to 0.5 m3 and from US$ 94.92 kg−1 to US$ 17.86 kg−1 when the cost of the raw materials decreased from US$ 7.91 kg−1 to US$ 0.85 kg−1 for a two 0.05 m3 extractor system.

Substantial genetic, biochemical, and in vivo data indicate that progressive accumulation of amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Historically centered in the importance of parenchymal plaques, the role of cerebral amyloid angiopathy (CAA)--a frequently neglected amyloid deposit present in >80% of AD cases--for the mechanism of disease pathogenesis is now starting to emerge. CAA consistently associates with microvascular modifications, ischemic lesions, micro- and macro-hemorrhages, and dementia, progressively affecting cerebral blood flow, altering blood-brain barrier permeability, interfering with brain clearance mechanisms and triggering a cascade of deleterious pro-inflammatory and metabolic events that compromise the integrity of the neurovascular unit. New evidence highlights the contribution of pre-fibrillar Aβ in the induction of cerebral endothelial cell dysfunction. The recently discovered interaction of oligomeric Aβ species with TRAIL DR4 and DR5 cell surface death receptors mediates the engagement of mitochondrial pathways and sequential activation of multiple caspases, eliciting a cascade of cell death mechanisms while unveiling an opportunity for exploring mechanistic-based therapeutic interventions to preserve the integrity of the neurovascular unit.

The goal of this study was to evaluate the effect of the dietary levels of Bacillus subtilis (BS) on performance, egg quality and excreta moisture of hens. A total of 240 Hy-line W-36 layers, between 25 and 45 weeks of age, were distributed according to a randomized block experimental design into 4 treatments with 10 replicates of 6 birds each. The following treatments were evaluated: basal diet with no probiotic (control, T1); basal diet containing BS at 8×10 5 CFU/g feed (T2); basal diet containing BS at 4×10 5 CFU/g feed (T3); and basal diet containing BS at 3×10 5 CFU/g feed (T4). Feed intake (FI), egg production (EP), egg weight (EW), egg mass (EM), feed conversion ratio per dozen eggs (FCRD) and feed conversion ratio per egg mass (FCRM), yolk, eggshell, albumen and excreta dry matter (EDM) content were evaluated. Feed intake, FCRD, and egg component were not influenced (P>0.05) by the treatments. Dietary supplementation with BS at 8×10 5 CFU/g feed compared to control increased (P 0.05) in FCRM. Excreta dry matter was on average 4.67% higher (P 5 CFU/g feed of B. subtilis improves the egg production and reduces excreta moisture of layers.