Without IPv6, there is no digital transformation for healthcare.

BACKGROUND: Originally, digital healthcare was created to support underserved and rural patients gain access to health services. Phones, devices, and computers need IP (Internet Protocol) addresses to connect to the Internet. OBJECTIVE: This paper aims to study the close relationship between the Internet and the transformation of healthcare services. METHODS: The current protocol in use is the Internet Protocol version 4 (IPv4), whose number of Internet addresses has been globally exhausted. The Internet Protocol version 6 (IPv6) with 47 octillion unique addresses for every person on the planet has become the only option for sustainable growth and innovation. However, most of the worldwide industry is still in IPv4. In the era of Artificial Intelligence, Internet of Things, Fifth Generation of Cellular Technology (5G), and Blockchain, there will be a massive need of IP addresses. For 2025, experts predict over 1.5 billion new IPv6 users which will continue to grow exponentially. RESULTS: Nations need to tackle the increasing industry requirements for IPv6 and telehealth adoption to benefit from the full IPv6 connectivity which is the key strategic advantage for the healthcare industry. CONCLUSION: The strategic potential that telehealth brings to the healthcare industry is widely appreciated. However, what are the implications of its expansion around the world? How can we prioritize the poorest and most vulnerable in society without new technologies?

Strecker aldehydes and α-keto acids, produced by carbonyl-amine reactions, contribute to the formation of acrylamide.

The formation and disappearance of acrylamide in binary and ternary mixtures of asparagine (or acrylamide), carbonyl compounds and amino acid derivatives was studied in an attempt to understand the different reactions produced in mixtures of carbonyl compounds and amino acids. The carbonyl compounds assayed included glucose, 2,4-decadienal, mercaptopyruvic acid, phenylpyruvic acid, and phenylacetaldehyde. The assayed amino acids were cysteine, N-acetylcysteine, and phenylalanine, in addition to asparagine. All assayed carbonyl compounds were able to convert asparagine into acrylamide to various extents, and some of them were more reactive than glucose. In addition, they inhibited the Michael additions responsible for acrylamide disappearance. On the other hand, the addition of amino acids mostly resulted in decreases of acrylamide, although acrylamide also increased in some mixtures. Amino acids decreased acrylamide yield because of both their competence with asparagine for carbonyl compounds and their reaction with the produced acrylamide. However, carbonyl-amine reactions formed new carbonyl compounds, which increased acrylamide content. Therefore, asparagine degradation in the presence of amino acids is likely to be a balance between the decrease of degradation produced by the original carbonyl compounds and the increase of degradation due to the carbonyl compounds formed.

Protective effect of phenolic compounds on carbonyl-amine reactions produced by lipid-derived reactive carbonyls.

The degradation of phenylalanine initiated by 2-pentenal, 2,4-heptadienal, 4-oxo-2-pentenal, 4,5-epoxy-2-heptenal, or 4,5-epoxy-2-decenal in the presence of phenolic compounds was studied to determine the structure-activity relationship of phenolic compounds on the protection of amino compounds against modifications produced by lipid-derived carbonyls. The obtained results showed that flavan-3-ols were the most efficient phenolic compounds followed by single m-diphenols. The effectiveness of these compounds was found to be related to their ability to trap rapidly the carbonyl compound, avoiding in this way the reaction of the carbonyl compound with the amino acid. The ability of flavan-3-ols for this reaction is suggested to be related to the high electronic density existing in some of the aromatic carbons of their ring A. This is the first report showing that carbonyl-phenol reactions involving lipid-derived reactive carbonyls can be produced more rapidly than carbonyl-amine reactions, therefore providing a satisfactory protection of amino compounds.

Antagonism between lipid-derived reactive carbonyls and phenolic compounds in the Strecker degradation of amino acids.

The Strecker-type degradation of phenylalanine in the presence of 2-pentanal and phenolic compounds was studied to investigate possible interactions that either promote or inhibit the formation of Strecker aldehydes in food products. Phenylacetaldehyde formation was promoted by 2-pentenal and also by o- and p-diphenols, but not by m-diphenols. This is consequence of the ability of phenolic compounds to be converted into reactive carbonyls and produce the Strecker degradation of the amino acid. When 2-pentenal and phenolic compounds were simultaneously present, an antagonism among them was observed. This antagonism is suggested to be a consequence of the ability of phenolic compounds to either react with both 2-pentenal and phenylacetaldehyde, or compete with other carbonyl compounds for the amino acids, a function that is determined by their structure. All these results suggest that carbonyl-phenol reactions may be used to modulate flavor formation produced in food products by lipid-derived reactive carbonyls.

Contribution of phenolic compounds to food flavors: Strecker-type degradation of amines and amino acids produced by o- and p-diphenols.

The ability of 20 phenolic derivatives to produce the Strecker-type degradation of phenylalanine and phenylglycine methyl ester was studied to investigate both the direct degradation of amino acids and amines by phenolic compounds in the absence of added oxidants and the effect of the number and positions of hydroxyl groups in the aromatic ring of the phenolic compound in relation to its ability to produce carbonyl derivatives from amino compounds. The obtained results showed that polyphenols can produce the Strecker degradation of amino acids and amines in the absence of added oxidants. The only requisite for producing the reaction is the presence of two hydroxyl groups in ortho or para positions. However, the presence of two hydroxyl groups in meta position in an additional aromatic ring can inhibit the Strecker-degrading ability of the hydroxyl groups in ortho or para positions. A reaction pathway that explains all of these findings is proposed. In addition, the effect of reaction conditions on the obtained reaction yields was studied. Activation energies (Ea) for phenylacetaldehyde formation from phenylalanine in the presence of hydroquinone, 1,2,4-trihydroxybenzene, and benzoquinone were 32.9, 31.5, and 28.8 kJ/mol, respectively.

Relationship between lutein and mycotoxin content in durum wheat.

Levels of lutein and a number of mycotoxins were determined in seven varieties of durum wheat (Triticum durum) and two varieties of common wheat (Triticum aestivum) in order to explore possible relationships amongst these components. Durum wheat cultivars always showed both higher lutein and mycotoxin contents than common wheat cultivars. The mycotoxins detected in both common and durum wheat cultivars were produced by the genera Fusarium, Claviceps, Alternaria and Aspergillus. Fusarium was the major producer of mycotoxins (26 mycotoxins) followed by Claviceps (14 mycotoxins), which was present only in some cultivars such as Chevalier (common wheat), Lupidur and Selyemdur (both durum wheat), Alternaria (six mycotoxins) and Aspergillus (three mycotoxins). Positive correlations between the levels of lutein and mycotoxins in durum wheat cultivars were found for the following mycotoxins: deoxynivalenol (DON), its derivative DON-3-glucoside, moniliformin, culmorin and its derivatives (5-hydroxyculmorin and 15-hydroxyculmorin).

Intermediate role of α-keto acids in the formation of Strecker aldehydes.

The ability of α-keto acids to covert amino acids into Strecker aldehydes was investigated in an attempt to both identify new pathways for Strecker degradation, and analyse the role of α-keto acids as intermediate compounds in the formation of Strecker aldehydes by oxidised lipids. The results obtained indicated that phenylalanine was converted into phenylacetaldehyde to a significant extent by all α-keto acids assayed; glyoxylic acid being the most reactive α-keto acid for this reaction. It has been proposed that the reaction occurs by formation of an imine between the keto group of the α-keto acid, and the amino group of the amino acid. This then undergoes an electronic rearrangement with the loss of carbon dioxide to produce a new imine. This final imine is the origin of both the Strecker aldehyde and the amino acid from which the α-keto acid is derived. When glycine was incubated in the presence of 4,5-epoxy-2-decenal, the amino acid was converted into glyoxylic acid, and this α-keto acid was then able to convert phenylalanine into phenylacetaldehyde. All these results suggest that Strecker aldehydes can be produced by amino acid degradation initiated by different reactive carbonyl compounds, included those coming from amino acids and proteins. In addition, α-keto acids may act as intermediates for the Strecker degradation of amino acids by oxidised lipids.

Determination of α-keto acids in pork meat and Iberian ham via tandem mass spectrometry.

An analytical method which offers accurate determination and identification of eight α-keto acids (α-ketoglutaric acid, pyruvic acid, 4-hydroxyphenylpyruvic acid, 3-methyl-2-oxobutyric acid, α-keto-γ-methylthiobutyric acid, 4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, and phenylpyruvic acid) in pork meat and Iberian ham samples is reported. The method utilises a highly selective and sensitive method of multiple reaction monitoring (MRM) by mass spectrometry. The analytical method is simple (although the chemical derivatisation of the α-keto acids with dansylhydrazine is required), precise (<18% RSD), accurate (90-110%), sensitive (0.01-0.34 mg/kg of defatted and freeze-dried meat depending on the α-keto acid) and linear (R>0.99) over several orders of magnitude (until 0.01-146.1 mg/kg of defatted and freeze-dried meat depending on the α-keto acid). Using this methodology, α-keto acids were found to be present in pork meat to a low extent, and their concentration increased when they were determined in Iberian ham. This is the first report of the presence of α-keto acids in both pork meats and Iberian hams.

Chemical conversion of phenylethylamine into phenylacetaldehyde by carbonyl-amine reactions in model systems.

The chemical conversion of phenylethylamine into phenylacetaldehyde in the presence of lipid oxidation products (LOPs) was studied to investigate the possibility that biogenic amines can be converted into Strecker aldehydes upon processing. Model systems of phenylethylamine and methyl 13-hydroperoxyoctadeca-9,11-dienoate (HP), 2,4-decadienal (DD), 4,5-epoxy-2-heptenal (EH), 4,5-epoxy-2-decenal (ED), 4-oxo-2-hexenal (OH), 4-oxo-2-nonenal (ON), or 4-hydroxy-2-nonenal (HN) were heated for 1 h at 180 °C and pH 3. Although HN and EH did not produce more phenylacetaldehyde than when phenylethylamine was heated alone, all other lipid oxidation products assayed increased the amount of phenylacetaldehyde produced by 300-900%, with ON being the most reactive compound for this reaction. The reaction was mainly produced at acidic pH values (<6) and was dependent upon the concentration of the LOPs involved, and the phenylacetaldehyde produced increased linearly as a function of the time and temperature. The E(a) values for the reactions between phenylethylamine and DD and ON were 54.8 and 53.8 kJ/mol, respectively. The reaction is proposed to take place by the formation of an imine between the phenylethylamine and the LOPs, which is later converted into another imine by an electronic rearrangement. This new imine is the origin of phenylacetaldehyde by hydrolysis. These results show a new pathway for Strecker aldehyde formation. This route provides a potential way to reduce biogenic amine content in foods when they can be thermally processed before consumption.

Model reactions of acrylamide with selected amino compounds.

The reaction of acrylamide with amines, amino acids, and polypeptides was studied in an attempt to understand the role of amino compounds on acrylamide fate. The obtained results showed that amino compounds are added to acrylamide by means of a Michael addition to produce the corresponding 3-(alkylamino)propionamides. Although 3-(alkylamino)propionamides can also be added to a new molecule of acrylamide to produce a new adduct, this last adduct was not detected under the employed conditions in which the concentration of acrylamide was much lower than the concentration of the amino compounds. The produced 3-(alkylamino)propionamides were not stable, and the addition reaction was easily reversed by heating. Thus, acrylamide was produced from 3-(alkylamino)propionamides by means of an elimination reaction. However, the activation energies (E(a)) of both reactions are not the same. In fact, acrylamide seems to be converted into its Michael adduct with a lower activation energy than the elimination reaction of the Michael adduct. For this reason, when acrylamide was stored in the presence of glycine at 60 degrees C, acrylamide disappeared after 14 days. However, when these samples were heated again for 20 min at 180 degrees C, the equilibrium was reestablished and a significant amount of acrylamide was detected. All of these results suggest that amino compounds may play a significant role in the changes observed in acrylamide content in foods upon storage. In addition, they also point to 3-(alkylamino)propionamides as possible compounds in which acrylamide might be potentially hidden.

Asparagine decarboxylation by lipid oxidation products in model systems.

The decarboxylation of asparagine in the presence of alkanals, alkenals, and alkadienals, among other lipid derivatives, was studied in an attempt to understand the reaction pathways by which some lipid oxidation products are able to convert asparagine into acrylamide. Asparagine was converted into 3-aminopropionamide in the presence of lipid derivatives as a function of reaction conditions (pH, water content, time, and temperature), as well as the type and amount of lipid compound involved. Alkadienals (and analogous ketodienes) were the most reactive lipids followed by hydroperoxides and alkenals. Saturated carbonyls and polyunsaturated fatty acids, or other polyunsaturated derivatives, also exhibited some reactivity. On the other hand, saturated lipids or monounsaturated alcohols did not degrade asparagine. A mechanism for the decarboxylation of asparagine in the presence of alkadienals based on the deuteration results obtained when asparagine/2,4-decadienal model systems were heated in the presence of deuterated water was proposed. The activation energy (E(a)) of asparagine decarboxylation by 2,4-decadienal was 81.0 kJ/mol, which is higher than that found for the conversion of 3-aminopropionamide into acrylamide in the presence of 2,4-decadienal. This result points to the decarboxylation step as the key step in the conversion of asparagine into acrylamide in the presence of alkadienals. Therefore, any inhibiting strategy for suppressing the formation of acrylamide by alkadienals should be mainly directed to the inhibition of this step.

Conversion of 3-aminopropionamide and 3-alkylaminopropionamides into acrylamide in model systems.

Carbonyl compounds have been shown to play a major role in the conversion of asparagine into acrylamide. However, it is unclear at this point if its role is only restricted to the decarboxylation of the amino acid or if carbonyl compounds also play a role in the deamination reaction of the decarboxylated intermediates 3-aminopropionamide and 3-(alkylamino)propionamides. This study describes the deamination reaction of 3-aminopropionamide and 3-(alkylamino)propionamides (benzyl, phenylethyl, butyl, and octyl) in model systems and in the presence, or not, of different carbonyl compounds (alkadienals, alkenals, and alkanals). All these reactions were mainly produced at almost neutral or basic pH values. In addition, the reaction yields and the activation energies not only depended on the type of aminopropionamide involved but also on the water activity (a(w)) and in the presence, or not, of carbonyl compounds. However, there was not a clear correlation among the activation energies calculated for the different deamination reactions and the yields of acrylamide obtained; therefore, suggesting the existence of diverse pathways by which 3-aminopropionamide and 3-(alkylamino)propionamides are converted into acrylamide. In addition, these reactions are also competing with other carbonyl-amine reactions when carbonyl compounds are present. All these results suggest that the type of the intermediate aminopropionamide involved is going to play a major role in both the amount of acrylamide produced and the conditions required for its formation. On the other hand, the role of carbonyl compounds in the acrylamide produced, but not in the activation energy of the reactions implicated, seems to be more limited than either the type of amine or the a(w). A detailed analysis of the type of the intermediate aminopropionamide formed in foods may help to define strategies for mitigating the formation of this food toxicant.