Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease

Background: Anderson-Fabry disease (AFD) is an X-linked disease that results from reduced activity of the enzyme galactosidase alpha (GLA). When the GLA gene sequence is altered by mutations that alter the normal DNA sequence, variants of the alpha-galactosidase A enzyme are produced, which may or may not function. These mutations are responsible for Fabry disease, and to date, over 800 different mutations of the gene have been described in patients with Anderson-Fabry disease. In this case, we report the case of a woman who is the sole family member with this type of mutation.Case presentation: We report a case of a 52-year-old woman with end-stage chronic kidney disease in dialysis treatment. The patient's alpha-galactosidase activity was 6.6 nmol/ml/h in whole blood, and lyso-GB3 levels were 11.45 nmol/L (normal range < 2.3 nmol/L). Alpha-galactosidase A gene sequence analysis revealed a pathogenic variant of c.947dupT in exon 6, leading to the p. I317NfsTer16 amino acid substitution. The genetic analysis did not detect the same mutation in any of the other screened family members.Conclusion: The international Fabry disease genotype-phenotype database (dbFGP) reports a pathogenic variant c.947dupT in exon 6 that is probably associated with a classical phenotype of Fabry disease. In this case report, we report the case of a woman who is the sole family member with this type of pathogenic variant. Similar situations have not been described in the literature for this pathogenic variant, and it represents an important case of inter- and intrafamilial variability in patients with Fabry disease. The literature shows that de novo pathogenic variants are frequently found in the context of Fabry disease

Water Collection and Distribution Systems in the Palermo Plain During the Middle Ages

It has been said that Palermo is short of available water. However, nothing could be more wrong. Well-documented Arab sources and narrative chronicles reported an abundance of groundwater resources in Palermo Plain since the Middle Ages. The scarcity of sources and surface water in the Palermo Plain, compared to the groundwater abundance, led the inhabitants to use groundwater both for irrigation and domestic usage through a complex and sustainable hydraulic system. Vertical and horizontal (qanāts) wells, conveyed water towards gardens and public fountains making the Arabic Bal’harm (Palermo) a flourishing town. When visitors walk through the streets of Palermo’s historical center, among Arab ruins and Baroque architecture, they hardly imagine that there is a wide and varied cultural heritage of underground cavities hidden in the basements where water flows in intricate networks fed from a numerous springs. Only in recent years was a part of this system brought to light. Moreover, the city still has a wide and fascinating water distribution system consisting of irrigation basin (gebbie), ingenious hydraulic machines named senie, and distribution chessboard of irrigation (saje) and drinking water (catusi) canals. The medieval water collection and distribution systems and their various components in the Palermo Plain are reviewed together with the influence of the Arab water management on environment

Focus on Olea europaea L. pruning by-products: extraction techniques, biological activity, and phytochemical profile

The Olea europaea L. tree has played a central role in Mediterranean culture since ancient times. Several studies have highlighted the health-promoting properties both of its primary products (olives) and its by-products (leaves, pomace, husk, stone, mill wastes, and wood). In this study, pruning residues from 25-year-old olive trees located in a Mediterranean region (Basilicata, Italy) were analyzed. The antioxidant activity of hydro-alcoholic extracts from wood samples were analyzed through three complementary in vitro assays. The molecular composition of the extracts was thoroughly evaluated using a gas chromatography apparatus coupled with a mass spectrometer (GC–MS). Our study demonstrated that all but three extracts had remarkable antioxidant activity, which was likely due to the meaningful presence of phenolic compounds, mostly derived from lignin. Moreover, the results showed that bark extracts obtained with ultrasound-assisted extraction (UAE) had the highest antioxidant activity. In this extract, several known compounds with demonstrated antioxidant activity were found, including hexylresorcinol, 1-methyl-N-vanillyl-2-phenethamine, and allopurinol. This research suggests that woody olive by-products are a potential natural resource of antioxidants. These compounds could be useful for functional foods and in industry, and could help to solve the problem of pruning residues, increasing their potential economic valu

Anti-Listeria activity of lactic acid bacteria in two traditional Sicilian cheeses

Listeria monocytogenes is a pathogen frequently found in dairy products, and its growth is difficult to control. Bacteriocin-like inhibitory substances (BLIS), produced by lactic acid bacteria (LAB), having proven in vitro anti-Listeria activity, could provide an innovative approach to control L. monocytogenes; however, this application needs to be evaluated in vivo. In this study, twenty LAB strains isolated from different Sicilian dairy environments were tested for control of growth of L. monocytogenes in three different experimental trials. First, raw and UHT milk were inoculated with LAB strains alone, and LAB strains mixed with L. monocytogenes. Second, mini-cheeses containing LAB and/or L. monocytogenes were produced. Third, two traditional Sicilian cheeses inoculated with a multi-strain LAB mixture combined with L. monocytogenes were produced. The addition of BLIS produced by LAB to milk and in mini-cheese production was unable to inhibit the growth of L. monocytogenes. However, an anti-Listeria effect was observed in the Pecorino Siciliano cheeses, where, after 15 days of ripening, the cheeses with added LAB had fewer L. monocytogenes compared to the control cheeses with no added LAB, while in the Vastedda della valle del Bel\uecce cheeses, the multi-strain LAB mixture completely prevented the growth of L. monocytogenes

Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approxi-mately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a signif-icant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the au-tophagy–lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal oc-clusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-de-pendent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibro-blasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in ad-dition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy

Amaranthus grain as a new ingredient in diets for dairy cows: productive, qualitative, and in vitro fermentation traits

BACKGROUND: In recent decades, grain amaranths have attracted attention due to their valuable combination of nutritional traits, with higher protein and oil content than conventional cereals. Before they can be proposed as an unconventional ingredient in animal feed, many aspects still need to be investigated from field production to nutritive value. The present research aimed to study the agronomic traits, proximate composition, and digestibility/degradability, fatty acid profile, antioxidant activity, and total phenolic content of two grain amaranth species, Amaranthus cruentus and Amaranthus hypochondriacus (for a total of six accessions), grown in a Mediterranean environment. RESULTS: Both species showed seed yields comparable to or higher than the traditional cereal crops in the same environment. On the whole, A. cruentus resulted in a higher seed production than A. hypochondriacus. Mexico and Montana accessions, both belonging to A. cruentus, showed the highest yield (3.73 t ha−1, on average). Few differences emerged in nutritive value between species and accessions: the Illinois accession of A. cruentus showed the best performance in terms of in vitro degradability and gas production, but not for volatile fatty acid production; the fermentation kinetics was slowest in the Illinois accession and fastest in the Montana accession of A. cruentus and the India accession of A. hypochondriacus. CONCLUSION: From a health perspective, the Nebraska accession of A. hypochondriacus represents the best accession, with the lowest saturated fatty acid content and the highest polyunsaturated fatty acid content. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Water as a solvent of election for obtaining oleuropein-rich extracts from olive (Olea europaea) leaves

Leaves from Olea europaea represent one of the main by-products of the olive oil industry, containing a plethora of bioactive compounds with several promising activities for human health. An organic solvent-free extraction method was developed for the recovery of olive leaf phenols, which obtained an extract containing oleuropein in high amounts. A comparison of various extraction media is reported, together with the total phenolic content, DPPH (2,2-Diphenyl-1-picrylhydrazyl) content, ORAC (oxygen radical absorbance capacity), and polyphenol oxidase activity of the corresponding extracts. The polyphenol profiles and content of the most representative extracts have also been studied. Extraction solvent and temperature significantly influenced the phenolic content and antioxidant activity of the extracts, with hot water representing the solvent of election for the extraction of bioactive compounds from this matrix. All the extracts obtained showed reasonably high total phenol content (TPC) and good DPPH radical scavenging activity; among them, the water extract is characterized by desirable traits and could be used for many industrial applications and human consumption

Ablation loading of barium ions into a surface electrode trap

Trapped-ion quantum information processing may benefit from qubits encoded in isotopes that are practically available in only small quantities, e.g. due to low natural abundance or radioactivity. Laser ablation provides a method of controllably liberating neutral atoms or ions from low-volume targets, but energetic ablation products can be difficult to confine in the small ion-electrode distance, micron-scale, microfabricated traps amenable to high-speed, high-fidelity manipulation of ion arrays. Here we investigate ablation-based ion loading into surface-electrode traps of different sizes to test a model describing ion loading probability as a function of effective trap volume and other trap parameters. We demonstrate loading of ablated and photoionized barium in two cryogenic surface-electrode traps with 730 $\mu$m and 50 $\mu$m ion-electrode distances. Our loading success probability agrees with a predictive analytical model, providing insight for the confinement of limited-quantity species of interest for quantum computing, simulation, and sensing

Determinants of intraregional migration in Sub-Saharan Africa 1980-2000

Despite great accomplishments in the migration literature, the determinants of South-South migration remain poorly understood. In an attempt to fill this gap, this paper formulates and tests an empirical model for intraregional migration in sub-Saharan Africa within an extended human capital framework, taking into account spatial interaction. Using bilateral panel data between 1980 and 2000, we find that intraregional migration on the subcontinent is predominantly driven by economic opportunities and sociopolitics in the host country, facilitated by geographical proximity. The role played by network effects and environmental conditions is also apparent. Finally, origin and destination spatial dependence should definitely not be ignored