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Understanding the functional attributes of meat proteins is crucial for determining their nutritional benefits. Depending on the form in which meat proteins are available, the digestive process can release peptides which are valuable for nutrition and may also possess bioactive properties, affecting physiology. Liquid chromatography - mass spectrometry (LC-MS) was used to quantitatively compare the molecular peptide features (representing non-redundant peptides), during the different stages of a simulated gastrointestinal digestion process of a minimally processed powdered meat and its enzymatically produced hydrolysate. Results from a principal component analysis (PCA) indicated that the hydrolysate did not undergo extensive additional digestion whereas the powdered meat was digested both at the gastric and in the intestinal phases. Bioactive peptide sequence prediction identified the meat hydrolysate but not the meat powder as the only source of exact and partial bioactive matches in the angiotensin-I converting enzyme and dipeptidyl peptidase IV inhibition categories. Also, a higher source of cryptides (encrypted bioactive peptides), indicated that meat hydrolysates are potentially a better substrate for the release of these enzyme inhibitory peptides. These observations thus suggest that pre-digestion of a complex food matrix such as meat, may enhance its bioavailability following oral consumption early in the digestion process. SIGNIFICANCE: This work highlights enzymatic hydrolysis of meat proteins prior to ingestion allows for potentially higher bioavailability of bioactive peptides that inhibit angiotensin-I converting enzyme and dipeptidyl peptidase IV, thus possibly aiding high blood pressure and type 2 diabetes management., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This scoping review aimed to identify patient goal elicitation and evaluation methods for older adults, and to investigate which methods can be used in medication optimization interventions for nursing home residents (NHRs)., Methods: The Arksey and O'Malley framework guided the review. A search was launched in PubMed, Embase, CINAHL, and Web of Science. Reference selection and data extraction were performed by three independent reviewers, followed by team discussions to solve discrepancies. Inductive thematic analysis was applied to synthesize the data. Included papers were reconsidered to identify methods for medication optimization interventions for NHRs., Results: Ninety-six references, encompassing 38 elicitation and 12 evaluation methods, were included. Elicitation methods differed in structure, content, and patient involvement levels. Qualitative and quantitative methods were found to assess goal attainment. Five elicitation and three evaluation methods were developed for NHRs, but none of these contained a medication-related assessment., Conclusion: A variety of goal elicitation and evaluation methods for older adults was found, but none for medication optimization interventions in NHRs., Practice Implications: A holistic approach seems important to integrate patient goals into medication optimization interventions, not limiting goal elicitation to a medication-related assessment. Also, the choice of assessor seems important to obtain patient goals., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

On average a human cell type expresses around 10,000 different protein coding genes synthesizing all the different molecular forms of the protein product (proteoforms) found in a cell. In a typical shotgun bottom up proteomic approach, the proteins are enzymatically cleaved, producing several 100,000 s of different peptides that are analyzed with liquid chromatography-tandem mass spectrometry (LC-MSMS). One of the major consequences of this high sample complexity is that coelution of peptides cannot be avoided. Moreover, low abundant peptides are difficult to identify as they have a lower chance of being selected for fragmentation due to ion-suppression effects and the semi-stochastic nature of the precursor selection in data-dependent shotgun proteomic analysis where peptides are selected for fragmentation analysis one-by-one as they elute from the column. In the current study we explore a simple novel approach that has the potential to counter some of the effect of coelution of peptides and improves the number of peptide identifications in a bottom-up proteomic analysis. In this method, peptides from a HeLa cell digest were eluted from the reverse phase column using three different elution solvents (acetonitrile, methanol and acetone) in three replicate reversed phase LC-MS/MS shotgun proteomic analysis. Results were compared with three technical replicates using the same solvent, which is common practice in proteomic analysis. In total, we see an increase of up to 10% in unique protein and up to 30% in unique peptide identifications from the combined analysis using different elution solvents when compared to the combined identifications from the three replicates of the same solvent. In addition, the overlap of unique peptide identifications common in all three LC-MS analyses in our approach is only 23% compared to 50% in the replicates using the same solvent. The method presented here thus provides an easy to implement method to significantly reduce the effects of coelution and ion suppression of peptides and improve protein coverage in shotgun proteomics. Data are available via ProteomeXchange with identifier PXD011908., (Copyright © 2019. Published by Elsevier B.V.)

Glucuronoxylomannogalactans (GXMGals) are characteristic capsular polysaccharides produced by the opportunistic fungus C. neoformans, which are implicated in cryptococcal virulence, via impairment of the host immune response. We determined for the first time the structure of a lipoglucuronomannogalactan (LGMGal), isolated from the surface of a mutant C. neoformans carrying a deletion in the UDP-GlcA decarboxylase gene. Monosaccharide composition and methylation analyses, as well as nuclear magnetic resonance spectroscopy were employed in discerning the structure. Our results show that the polysaccharide structure of the LGMGal differs from GXMGal by the absence of xylose and 2-O-acetylated mannose residues. LGMGal consists of a galactan main chain -[-6-α-Gal-]-, where every second Gal residue is substituted at O-3 with an oligosaccharide α-Man6OAc-3-α-Man-4-(β-GlcA-3)-β-Gal-; components in italic being non-stoichiometric. The substitution rate of β-Galp units by GlcpA is 35%. Additionally, we determined that the glycolipid anchor of the LGMGal is based on an myo-inositol phosphoceramide composed of C 18 -phytosphingosine and monohydroxylated lignoceric acid (2OHC 24:0 fatty acid)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

-Omics data have become indispensable to systems biology, which aims to describe the full complexity of functional cells, tissues, organs and organisms. Generating vast amounts of data via such methods, researchers have invested in ways of handling and interpreting these. From the large volumes of -omics data that have been gathered over the years, it is clear that the information derived from one -ome is usually far from complete. Now, individual techniques and methods for integration are maturing to the point that researchers can focus on network-based integration rather than simply interpreting single -ome studies. This review evaluates the application of integrated -omics approaches with a focus on Caenorhabditis elegans studies, intending to direct researchers in this field to useful databases and inspiring examples., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Biopharmaceutical companies face multiple external pressures. Shareholders demand a profitable company while governments, nongovernmental third parties, and the public at large expect a commitment to improving health in developed and, in particular, emerging economies. Current industry commercial models are inadequate for assessing opportunities in emerging economies where disease and market data are highly limited., Objective: The purpose of this article was to define a conceptual framework and build an analytic decision-making tool to assess and enhance a company's global portfolio while balancing its business needs with broader social expectations., Methods: Through a case-study methodology, we explore the relationship between business and social parameters associated with pharmaceutical innovation in three distinct disease areas. The global burden of disease-based theoretical framework using disability-adjusted life-years provides an overview of the burden associated with particular diseases. The social return on investment is expressed as disability-adjusted life-years averted as a result of the particular pharmaceutical innovation. Simultaneously, the business return on investment captures the research and development costs and projects revenues in terms of a profitability index., Conclusions: The proposed framework can assist companies as they strive to meet the medical needs of populations around the world for decades to come., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Lactobacillus helveticus is traditionally used in dairy industry as a starter or an adjunct culture for manufacture of cheese and some types of fermented milk. Its autolysis releases intracellular enzymes which is a prerequisite for optimum cheese maturation, and is known to be strain dependent. Autolysis is caused by an enzymatic hydrolysis of the cell wall peptidoglycan (PG) by endogenous peptidoglycan hydrolases (PGHs) or autolysins. Origins of differences in autolytic properties of different strains are not fully elucidated. Regulation of autolysis possibly depends on the structure of the cell wall components other than PG, particularly polysaccharides. In the present work, we screened six L. helveticus strains with different autolytic properties: DPC4571, BROI and LH1. We established, for the first time, that cell walls (CWs) of these strains contained polysaccharides, different from their CW teichoic acids. Cell wall polysaccharides of three strains were purified, and their chemical structures were established by 2D NMR spectroscopy and methylation analysis. The structures of their repeating units are presented., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The article takes a three-dimensional approach (triangulation) in defining international pricing policy for pharmaceuticals using cost-effectiveness analysis (CEA), willingness-to-pay (WTP) analysis, and ability-to-pay (ATP) analysis. It attempts to find a balance between the various economic methods of which some focus on effectiveness while others are geared toward incorporating equity in the equation., Methods: A critical review of the first two established economic methods and their ability to evaluate not only "efficacy" but also "fairness" in pricing decisions identifies a gap in the latter. Therefore, a third analytic method is presented that measures the ATP based on a country's score in the human development index of the United Nations Development Program for 120 countries. This approach allows practicing differential pricing among and within countries. To refine this equity-driven pricing concept, two additional parameters can be added to the model: the Oxford "Multidimensional Poverty Index" and the "Out-of-Pocket" or "Self Pay" health expenditure as reported by the World Bank., Results: There is no hierarchy between the above three pricing methods. Because one method provides further insight into the other, however, it is recommended to start with CEA followed by WTP analysis. These types of analysis are closely linked in that the first provides the CE ratio for the compound investigated and the other sets the anticipated ceiling threshold of the payer's WTP (in a particular country). The ATP method provides a supplementary "equity" check and facilitates the process of equity-based differential pricing., Conclusions: A third method should be used in conjunction with the standard CEA and WTP analysis that measures the ATP with the human development index as yardstick to provide sustainable and equitable access to medicines. We recommend that ATP analysis becomes an additional practice in policy decision making and in defining international pricing strategies for pharmaceuticals., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Although insects are among the most diverse groups of the animal kingdom and may be found in nearly all environments, one can observe an obvious lack of structural data on their glycosylation ability. Hymenoptera is the second largest of all insect orders with more than 110,000 identified species and includes the most famous examples of social insects' species such as wasps, bees and ants. In this report, the structural variety of O-glycans has been studied in two Hymenoptera species. In a previous study, we showed that major O-glycans from common wasp (Vespula germanica) salivary mucins correspond to T and Tn antigen, eventually substituted by phosphoethanolamine or phosphate groups. More detailed structural analysis performed by mass spectrometry revealed numerous minor O-glycan structures bearing Gal, GlcNAc, GalNAc and Fuc residues. Thus, in order to investigate glycosylation diversity in insects, we used common wasp nest (V. germanica) and hornet nest (Vespa cabro) as starting materials. These materials were submitted to reductive β-elimination and the released oligosaccharide-alditols further fractionated by multidimensional HPLC. Tandem mass spectrometry analyses combined with NMR data revealed the presence of various families of complex O-glycans differing accordingly to both core structures and external motifs. Glycans from wasp were characterized by the presence of core types 1 and 2, Lewis X and internal Gal-Gal motifs. We also observed unusual O-glycans containing a reducing GalNAc unit directly substituted by a fucose residue. In contrast, hornet O-glycans appeared as a rather homogeneous family of core 1 type O-glycans extended by galactose oligomers., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

(1)H NMR is now a standard method to determine de novo primary sequence of all sorts of glycans. These last 30 years, tens of thousands of oligosaccharide sequences have been elucidated by NMR spectroscopy in conjunction with other physico-chemical methods including mass spectrometry and gas chromatography. Most of these sequences are now compiled and available in several web databases recently unified in publicly available GlycomeDB, along with sets of experimental data. However, because the search for an exact sequence exclusively based on proton chemical shifts is sometimes delicate for NMR non-specialists, we worked out a new type of query, named SOACS, which allows the easy retrieval of existing sequences. This query is based on the readily distinguished (1)H chemical shifts from any (1)H NMR spectrum, and was designed to be usable to the widest scientist community.

We describe here the structural deciphering of four wasp O-glycans. Following purification of a mixture of glycoproteins from nests of the common wasp Vespula germanica L. (Hymenoptera), their substituting O-glycans were liberated by reducing beta-elimination and characterised using a combination of high resolution NMR and mass spectrometry analyses. Besides ubiquitously found in the insect cells GalNAc-ol and Gal(beta1-3)GalNAc-ol compounds, two novel O-glycans carrying a 2-aminoethyl phosphate group were described for the first time here. We suggest that they present the following structures: Etn-P-(O-->6)-GalNAc-ol and Etn-P-(O-->6)-[Gal(beta1-3)]GalNAc-ol. In conjunction with previous studies, these results suggest that a 2-aminoethyl phosphate group may act as an alternative to sialic acid for conferring charges to glycoproteins.

To date, the enzymatically-catalysed synthesis of pentose-containing compounds has been limited to the production of oligo-beta-(1-->3) and oligo-beta-(1-->4)-linked xylopyranosides. To our knowledge, no such syntheses have involved arabinofuranose or, indeed, any other sugars in the furanose configuration. In this report, we describe the use of a thermostable alpha-L-arabinofuranosidase for the synthesis of p-nitrophenyl alpha-L-arabinofuranosyl-(1-->2)-alpha-L-arabinofuranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->2)-beta-D-xylopyranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranoside and benzyl alpha-D-xylopyranosyl-(1-->2)-alpha-L-arabinofuranoside. Importantly, this latter compound is synthesised in a highly regiospecific reaction, which leads to the production of a single disaccharide.

This study deals with the chemical characterization of an extracellular polysaccharide produced by the unicellular red alga Porphyridium sp. The sugar moiety of this polymer is composed of three neutral monosaccharides (Xyl, Glc, and Gal) and one uronic acid (GlcA). Proteins represent 5.5% of the dry weight of the polymer. Uronic degradation of this exopolysaccharide with lithium in ethylenediamine yielded two different oligosaccharides. The absolute configuration of the constitutive monosaccharides was chemically determined and revealed the presence of D-Xyl, D-Glc, D-, and L-Gal. The following oligosaccharide structures were established by NMR spectroscopy: [carbohydrate structure: see text].

The jelly coat surrounding the eggs of amphibia is composed of oviducal mucins and plays an important role in the fertilization process. From a structural and chemical point of view, these jellies are very different from one species to another. Bufo viridis is the 13th amphibia species studied in term of carbohydrate structural analysis. The oligosaccharides have been released from the oviducal mucins by reductive beta elimination, purified by various chromatography procedures and analyzed by (1)H and (13)C 1D-2D NMR spectroscopy. Among the 15 compounds, ten have novel structures, although they possess some well-known structural patterns as blood group epitopes (Le(x), Le(y)) or other sequences already observed in other amphibia species. These results reinforce our hypothesis about the strict species-specificity of these carbohydrate chains. It must be noted that such species-specificity does not depend on one particular monosaccharide but it is rather due to a set of particular tri- or tetrasaccharide sequences. Hence, B. viridis species could be characterized by the simultaneous presence of a 2,3,6-trisubstituted galactosyl residue, the GlcNAc(beta 1-3)[Fuc(alpha 1-4)]GlcNAc beta sequence and the Le(x), Le(y) or Cad determinants. The anionic charge of the oligosaccharides is carried only by sialic acid alpha-(2-->6)-linked to GalNAc-ol residue as in Bufo bufo or in Bufo arenarum.

The most common method used for the liberation of monosaccharides from glycoprotein N-glycans involves anhydrous methanolysis because it liberates almost quantitatively monosaccharides as O-methylglycosides, which are resistant to further degradation. However, it is generally assumed that this method does not cleave quantitatively the N-glycosidic bonds. This paper demonstrates that classical methanolysis conditions quantitatively cleave the N-glycosidic bond (96%), liberating glucosamine (and not its O-methylglycosides) and other minor reaction products which were identified. Because other N-acetyl-d-glucosamine (GlcNAc) residues are quantitatively liberated as the O-methylglycosides of glucosamine, the GlcNAc residue involved in the N-glycosidic bond is separated from the others using gas chromatography of heptafluorobutyrate derivatives., (Copyright 1999 Academic Press.)

The mucins isolated from Rana temporaria egg jelly coats were found to be composed of Gal, Fuc, GlcNac, GalNAc and GlcA acid. The primary structure of seven sulfated oligosaccharide-alditols was obtained by 1D/2D NMR analyses (1H-13C). The results show the presence of the sulfate monosaccharides. HSO3(3)Gal, HSO(6)GlcNAc and HSO3(3)GlcA. The sequence HSO3(3)GlcA (beta1-3)Gal, which constitutes the major determinant of the HNK-1 oncofoetal epitope, was characterized.

To examine the relationship between exogenous estrogen administration and endometrial cancer, we used data from the Cancer and Steroid Hormone Study, a multicenter, population-based case-control study. Estrogen replacement therapy for greater than or equal to 2 years was associated with an increased risk of both localized and extrauterine cancer (relative risk = 2.8, 95% confidence limits 1.6, 4.6; relative risk = 2.9, 95% confidence limits 0.9, 9.4, respectively). However, the latter finding was based on a small number of cases in which estrogen was used. Women who underwent estrogen replacement therapy for greater than or equal to 2 years had significantly elevated risks of endometrial cancer (2.1 for 2 to 5 years and 3.5 for greater than or equal to 6 years). An elevated risk persisted for greater than or equal to 6 years after discontinuation of therapy. Women who exclusively used conjugated equine estrogen preparations less than or equal to 0.625 mg had no increased risk of endometrial cancer. A history of oral contraceptive use appeared to reduce the risk of endometrial cancer associated with estrogen replacement therapy. However, these latter two potentially important findings were based on a small number of cases in which hormones were used.

A case of MEN type IIa is described showing among other symptoms, three attacks of transient neurological symptoms. These were attributed to a localized, transient cerebral ischemia. The latter probably developed as a consequence of the concomitant occurrence of different phenomena: the existence of hypercalcemia and on the other hand the secretion of vasoactive substances by one of the three tumours forming the MEN type IIa syndrome. The pheochromocytoma played an essential role because the symptoms did not recur after the bilateral adrenalectomy.

Medroxyprogesterone acetate (MPA), a potent progestagen, is used as a very efficient contraceptive agent. The method of administration is by a threemonthly or sixmonthly intramuscular injection. The method is particularly convenient when the desired number of children has been reached. Fertility is sometimes reestablished only slowly after stopping the injections. The main side effects are linked to endometrial atrophy (blood loss, amenorrhoea). Other side effects are infrequent and subjective. A controversy has risen over the product, by reference to its effects on beagle dogs. We have reviewed the literature. We also present the characteristics of 313 patients treated during (all together) 8,000 months. These patients belong to a rather poor sample of the population (amongst them many immigrant women), aged about 30, with above average pregnancy and parity rates. We also studied, in 31 patients, serum levels of glucose and lipids, and haemostasis. Side effects and reasons for discontinuing the drug are reported. The Pearl index was 0,75% women-years. There was no average effect on weight, blood tension, glycemia. Triglycerides increased slightly, and there was a discreet activation of coagulation with inhibition of the fibrinolytic activity, but without clinical consequences. We conclude that we can go on prescribing the drug, in view of our study and after reviewing the literature.