A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study).

OBJECTIVES: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. METHODS: FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. RESULTS: Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. CONCLUSION: Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses. CLINICAL TRIAL REGISTRATION: ACTRN12621001063808.

Minor Stroke Syndromes in Large-Vessel Occlusions: Mechanical Thrombectomy or Thrombolysis Only?

While mechanical thrombectomy for large-vessel occlusions is now an evidence-based treatment, its efficacy and safety in minor stroke syndromes (NIHSS ≤ 5) is not proved. We identified, in our prospective data base, 378 patients with minor strokes in the anterior circulation; 54 (14.2%) of these had proved large-vessel occlusions. Eight of 54 (14.8%) were immediately treated with mechanical thrombectomy, 6/54 (11.1%) after early neurologic deterioration, and the rest were treated with standard thrombolysis only. Rates of successful recanalization were similar between the 2 mechanical thrombectomy groups (75% versus 100%). Rates of excellent outcome (modified Rankin Scale 0-1) were higher in patients with immediate thrombectomy (75%) compared with patients with delayed thrombectomy (33.3%) and thrombolysis only (55%). No symptomatic intracranial hemorrhage occurred in either group. These descriptive data are encouraging, and further analysis of large registries or even randomized controlled trials in this patient subgroup should be performed.

[Health literacy among less well-educated young people: Influencing factors and consequences]. / Gesundheitskompetenz bildungsferner Jugendlicher : Einflussfaktoren und Folgen.

OBJECTIVES: Health literacy is known to influence health. Findings on the unequal distribution of health literacy among less well-educated young people are presented. The influence of socio-demographic factors and the consequences of a low level of health literacy with regard to health-related behaviour are discussed. MATERIALS AND METHODS: Data from a survey on the health literacy of young people with a lower level of education, older people and migrants (n = 1,000) were used. Health literacy was measured using the instruments of the European Health Literacy Survey (HLS-EU-Q47). RESULTS: The results demonstrate a lower level of health literacy among young people with less education and especially among young migrants. Explanations for a lower level of health literacy among young people with less well-educated young people were parents' educational background and parents' wealth. Migration-related factors had no influence on young people. Further correlations between health literacy and health behaviour were explored. CONCLUSION: It is concluded that health literacy is linked to health behaviour and that unequal distributions of health literacy among young people may increase health inequalities.

[How do citizens in Germany assess their own Health Literacy?]. / Wie bewerten Bürger in Deutschland ihre eigene Health Literacy?

Health literacy is a relatively recent concept in Europe. First international investigations indicate that a substantial part of the population has significantly impaired subjective health literacy. In Germany there is a lack of meaningful data. Therefore, 2 comprehensive studies have been started that will provide population representative results, as well as take the health literacy level of vulnerable groups such as older people and migrants into consideration.

Evolution of milk oligosaccharides and lactose: a hypothesis.

Mammalian milk or colostrum contains up to 10% of carbohydrate, of which free lactose usually constitutes more than 80%. Lactose is synthesized within lactating mammary glands from uridine diphosphate galactose (UDP-Gal) and glucose by a transgalactosylation catalysed by a complex of ß4-galactosyltransferase and α-lactalbumin (α-LA). α-LA is believed to have evolved from C-type lysozyme. Mammalian milk or colostrum usually contains a variety of oligosaccharides in addition to free lactose. Each oligosaccharide has a lactose unit at its reducing end; this unit acts as a precursor that is essential for its biosynthesis. It is generally believed that milk oligosaccharides act as prebiotics and also as receptor analogues that act as anti-infection factors. We propose the following hypothesis. The proto-lacteal secretions of the primitive mammary glands of the common ancestor of mammals contained fat and protein including lysozyme, but no lactose or oligosaccharides because of the absence of α-LA. When α-LA first appeared as a result of its evolution from lysozyme, its content within the lactating mammary glands was low and lactose was therefore synthesized at a slow rate. Because of the presence of glycosyltransferases, almost all of the nascent lactose was utilized for the biosynthesis of oligosaccharides. The predominant saccharides in the proto-lacteal secretions or primitive milk produced by this common ancestor were therefore oligosaccharides rather than free lactose. Subsequent to this initial period, the oligosaccharides began to serve as anti-infection factors. They were then recruited as a significant energy source for the neonate, which was achieved by an increase in the synthesis of α-LA. This produced a concomitant increase in the concentration of lactose in the milk, and lactose therefore became an important energy source for most eutherians, whereas oligosaccharides continued to serve mainly as anti-microbial agents. Lactose, in addition, began to act as an osmoregulatory molecule, controlling the milk volume. Studies on the chemical structures of the milk oligosaccharides of a variety of mammalian species suggest that human milk or colostrum is unique in that oligosaccharides containing lacto-N-biose I (LNB) (Gal(ß1 → 3)GlcNAc, type I) predominate over those containing N-acetyllactosamine (Gal(ß1 → 4)GlcNAc, type II), whereas in other species only type II oligosaccharides are found or else they predominate over type I oligosaccharides. It can be hypothesized that this feature may have a selective advantage in that it may promote the growth of beneficial colonic bacteria, Bifidobacteria, in the human infant colon.

Semihard scattering unraveled from collective dynamics by two-pion azimuthal correlations in 158A GeV/c Pb+Au collisions.

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-p(T) pions (p(T)>1 GeV/c) have been measured close to midrapidity in 158A GeV/c Pb+Au collisions by the CERES experiment. Elliptic flow (v(2)) rises linearly with p(T) to a value of about 10% at 2 GeV/c. Beyond p(T) approximately 1.5 GeV/c, the slope decreases considerably, possibly indicating a saturation of v(2) at high p(T). Two-pion azimuthal anisotropies for p(T)>1.2 GeV/c exceed the elliptic flow values by about 60% in midcentral collisions. These nonflow contributions are attributed to nearside and back-to-back jetlike correlations, the latter exhibiting centrality dependent broadening.

A multicenter, matched case-control study of risk factors for equine laminitis.

Risk factors for equine laminitis were examined in a prospective case-control study of the 258 cases seen at six collaborating veterinary teaching hospitals over a 32-month period. Case-control pairs were matched on institution, clinician, and season of diagnosis. The 90% of case-control pairs (78 acute, 155 chronic) that had complete data for age, gender, and breed were used in separate conditional logistic-regression models for acute and chronic laminitis. There was an increase in risk for horses with acute laminitis from 5 to 7 years of age (OR 4.7, 95% CI 1.3-16) and from 13 to 31 years of age (OR 3.9, 95% CI 1.3-12) (both compared to <5 years); risk was increased for chronic laminitis from 10 to 14 years (OR 3, 95% CI 1.4-6.8) and from 15 to 38 years (OR 2.9, 95% CI 1.4-6.1) (both compared to <6 years). Mares - but not stallions - were more likely than geldings to develop acute laminitis (OR 2.6, 95% CI 1.1-6.2) and chronic laminitis (OR 2.0, 95% CI 1.1-3.6). In the small acute-laminitis data set, the breed variable was collapsed into three categories: Thoroughbred (THB, reference), the Quarter Horse (QH), and other (non-QH-THB). The non-QH-THB group was at increased risk of acute laminitis (OR 3.8, 95% CI 1.2-11.8). For the seven breed-group categories used in the chronic-laminitis model, however, all non-THB breed groups appeared significantly at risk as compared to the THB, with odds ratios ranging from 3.3 (95% CI 1.3-8.30) for the QH to 9.1 (95% CI 2.1-39.3) for ponies.

Oligosaccharides of milk and colostrum in non-human mammals.

Mammalian milk or colostrum usually contains, in addition to lactose, a variety of neutral and acidic oligosaccharides. Although the oligosaccharides of human milk have been reviewed in several recent publications, those of non-human mammals have received much less attention. This paper reviews the chemical structures and the variety of milk oligosaccharides in species other than humans, including placental mammals (e.g. primates, domestic herbivores, bears and other carnivores, the rat and the elephant) as well as monotremes (platypus and echidna) and marsupials (e.g. wallaby). The gastrointestinal digestion and absorption and the possible biological functions of these oligosaccharides are also discussed.

Galactan biosynthesis in snails: a comparative study of beta-(1--> 6) galactosyltransferases from Helix pomatia and Biomphalaria glabrata.

Adult snails synthesize in their albumen glands a polysaccharide which is composed exclusively of D- or D- and L-galactose (Gal) residues which are interglycosidically linked by 1 --> 3 and 1 --> 6 bonds. It is the only carbohydrate source for embryos and freshly hatched snails. Two galactosyltransferases are described in this study which are most likely involved in the biosynthesis of this polysaccharide. One identified in Helix pomatia acts on oligosaccharides and could be used to synthesize a tetrasaccharide when the branched trisaccharide D-Gal-beta-(1 --> 3)-[D-Galbeta-(1 --> 6)]-D-Galbeta-1 --> OMe was offered as acceptor. This enzyme, requiring Mg++-and Mn++-ions for activity, introduced a linear beta-(1 --> 6) linkage at the terminal non-reducing ends and was not detected in Biomphalaria glabrata. The other enzyme, which introduced beta-(1 --> 6) linkages at subterminal D-Gal residues, thus forming branching points in the polysaccharide, was found in H. pomatia, Arianta arbustorum and B. glabrata with comparable activities. With the enzyme preparation of H. pomatia, up to four D-Gal residues were introduced into vicinal positions, forming single-membered side chains, if a hexasaccharide with five linearly beta-(1 --> 3)-linked D-Gal residues was offered as a acceptor. The multiple-branched structure formed is typical for snail galactans, making this enzyme a prime candidate for the branching enzyme in galactan synthesis. The enzyme activity could be solubilized and purified by affinity chromatography. In SDS-polyacrylamide electrophoresis, the Helix-derived eluate displayed two bands (68, 37 kDa) and that of Biomphalaria five bands (68, 63, 17.5; 15; 13 kDa). The purified material showed only 8% of the total activity of the crude extracts, but it could be shown that a phosphatase present in the crude extract can degrade UDP formed in the transfer reaction and thus drive the reaction to completion.

Use of evidence-based practice management guidelines in trauma care.

A PMG is a tool developed by a consensus process, with the input of all trauma care practitioners who are involved in the care of a patient with a specific clinical issue. The group that develops the PMG uses current, evidence-based data, carefully introduces and monitors the PMG in the clinical setting, and evaluates the success of the PMG in accomplishing the goals identified at the beginning of the process. The ultimate goal of a PMG is to eliminate unnecessary practice variations, with the end point of achieving quality care. Participating in the development of a guideline with a review of the literature serves as an excellent educational process for all practitioners.

Chemical characterisation of six oligosaccharides in a sample of colostrum of the brown capuchin, Cebus apella (Cebidae: primates).

Carbohydrates were extracted from a sample of brown capuchin colostrum and six of the component oligosaccharides were separated and purified by gel filtration and preparative thin layer chromatography. Their structures were determined by 1H-NMR to be as follows: Gal beta 1-->4[Fuc alpha 1-->3]Glc (3-fucosyllactose) Gal beta 1-->3Gal beta 1-->4Glc (beta-3'-galactosyllactose) Gal beta 1-->6Gal beta1-->4Glc (beta-6'-galactosyllactose) Gal beta-->3[Gal beta 1-->4GlcNAc beta 1-->6]Gal beta 1-->4Glc (lacto-N-novopentaose I) Gal beta 1-->4GlcNAc beta 1-->3[Gal beta 1-->4GlcNAc beta 1-->6]Gal beta 1-->4Glc (lacto-N-neohexaose) Neu5Ac alpha 2-->3Gal beta 1-->4Glc (3'-N-acetylneuraminyllactose) Of these, all except lacto-N-novopentaose I have been previously found in human milk or colostrum.

Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test.

OBJECTIVE: We hypothesized that human milk oligosaccharides (HMO) would not be digested and absorbed in the infant small intestine. The purpose of the study was to quantify the extent of digestion by using the lactulose breath hydrogen test. STUDY DESIGN: Twenty-four healthy, breast-fed infants were studied in the home setting. Eight infants (mean age 5.2 months) who had a positive breath hydrogen response (rise > 20 ppm) to the unabsorbable sugar lactulose were given an equivalent load of HMO (0.7 to 1.0 gm/kg body weight) the following week. The breath hydrogen response to the HMO load was compared with that after lactulose by using a paired t test. RESULTS: In seven of the eight infants, a large proportion of the HMO load reached the large intestine and was fermented. In these infants, the mean +/- SEM area under the breath hydrogen curve after HMO (5135 +/- 1148 ppm.4h) was not significantly different from that after lactulose (4949 +/- 1278 ppm.4h, p = 0.7s. CONCLUSIONS: This study suggests that HMO resist digestion in the small intestine of most breast-fed infants and undergo fermentation in the colon. HMO may therefore be the source of breath hydrogen in breast-fed infants.

Structure of the calcium-binding echidna milk lysozyme at 1.9 A resolution.

A lysozyme isolated from the milk of a monotreme, the echidna, Tachyglossus aculeatus multiaculeatus, has been crystallized (space group P2(1), with unit-cell dimensions a = 37.1, b = 42.0, c = 38.1 A, beta = 91 degrees and Z = 2) and the structure refined to an R value of 0.167 for all measured data in the resolution range 7.0-1.9 A. It had previously been inferred from sequence homology with alpha-lactalbumins that echidna milk lysozyme (EML) would bind one calcium ion per molecule. This has been confirmed in the present study in which the largest peak in a difference Fourier synthesis is associated with a calcium ion. The calcium binding site of EML is very similar to that observed in baboon and human alpha-lactalbumins, and in a human lysozyme engineered to contain a calcium-binding site. The overall fold of the protein is similar to that of chick-type lysozymes. EML, like pigeon lysozyme, has only 125 residues terminating at a cysteine but in EML this forms a disulfide with a cysteine at residue 9 whereas the equivalent cysteine residue in all other lysozymes of known sequence occurs at position 6. These changes cause some minor structural rearrangements. The binding of calcium appears to have had little effect on the polypeptide backbone conformation and caused only small changes in the conformation of side chains coordinating the calcium ion. A homology modelling study [Acharya, Stuart, Phillips, McKenzie & Teahan (1994). J. Protein Chem. 13(6), 569-584] correctly predicted the overall structure of EML and the nature of its calcium binding site but generally failed to model some more subtle differences observed in the EML structure as evidenced by the fact that the homology model more closely resembles the starting structure from which the model was derived than it does the crystal structure.

Chemical characterization of milk oligosaccharides of the brown bear, Ursus arctos yesoensis.

Two tri-, two hexa- and two deca-saccharides were isolated from bear milk by chloroform/methanol extraction and gel filtration. The oligosaccharides were characterized, mainly by 1H-NMR, as follows: [structures: see text]. Both trisaccharides were present in bear milk at a higher concentration than lactose.

Identification of 2'-fucosyllactose in milk of the crabeater seal (Lobodon carcinophagus).

1. An oligosaccharide was isolated from extracts of crabeater seal milk by preparative paper chromatography. 2. The saccharide was identified as Fuc alpha 1-2Ga1 beta 1-4G1c by 1H-NMR spectroscopy. 3. This work represents the first identification of an oligosaccharide, other than lactose, in the milk of a pinniped.

Lactose synthesis in a monotreme, the echidna (Tachyglossus aculeatus): isolation and amino acid sequence of echidna alpha-lactalbumin.

alpha-Lactalbumin and lysozyme were each isolated from echidna (Tachyglossus aculeatus) milk by gel permeation and ion exchange chromatography. The alpha-lactalbumin modified the action of echidna milk galactosyltransferase to promote the synthesis of lactose but had very little effect on bovine galactosyltransferase. Echidna alpha-lactalbumin is a glycosylated protein with an apparent molecular weight of 20,000 (SDS-PAGE) whose concentration in the milk is very low compared with the concentrations of alpha-lactalbumin in the milk of other species. Its amino acid sequence is more similar to that of another monotreme, the platypus (Ornithorhynchus anatinus), than to the sequences of eutherian or marsupial alpha-lactalbumins. Echidna milk lysozyme, even at high concentrations, did not promote the synthesis of lactose by either echidna or bovine galactosyltransferase. We conclude that lactose synthesis in the echidna occurs by the same mechanism as that found in the platypus and other mammals.