Progress and status of APEmille

We report on the progress and status of the APEmille project: a SIMD parallel computer with a peak performance in the TeraFlops range which is now in an advanced development phase. We discuss the hardware and software architecture, and present some performance estimates for Lattice Gauge Theory (LGT) applications.Comment: Talk presented at LATTICE97, 3 pages, Late

Oral Supplementation With Sucrosomial Ferric Pyrophosphate Plus L-Ascorbic Acid to Ameliorate the Martial Status: A Randomized Controlled Trial

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient's functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient's tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients ( 65 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost -2.8 \ub1 5.1%, while the intervention group gained +0.7 \ub1 4.6% of circulating hemoglobin from baseline (p = 0.019). Gastrointestinal diseases, medications, and possible dietary factors could affect the efficacy of iron supplements. Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors

Purpose Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease. Methods Eighteen male volunteers (ages 47.8 ? 9.7 years; body mass index 24.8 ? 2.6 kg/m2) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed. In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial functio

Modulation of fecal clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults

Background: The modulation of gut microbiota is considered to be the first target to establish probiotic efficacy in a healthy population. Objective: This study was conducted to determine the impact of a probiotic on the intestinal microbial ecology of healthy volunteers. Methods: High-throughput 16S ribosomal RNA gene sequencing was used to characterize the fecal microbiota in healthy adults (23-55 y old) of both sexes, before and after 4 wk of daily consumption of a capsule containing at least 24 billion viable Lactobacillus paracasei DG cells, according to a randomized, double-blind, crossover placebo-controlled design. Results: Probiotic intake induced an increase in Proteobacteria (P = 0.006) and in the Clostridiales genus Coprococcus (P = 0.009), whereas the Clostridiales genus Blautia (P = 0.036) was decreased; a trend of reduction was also observed for Anaerostipes (P = 0.05) and Clostridium (P = 0.06). We also found that the probiotic effect depended on the initial butyrate concentration. In fact, participants with butyrate >100 mmol/kg of wet feces had a mean butyrate reduction of 49 ± 21% and a concomitant decrease in the sum of 6 Clostridiales genera, namely Faecalibacterium, Blautia, Anaerostipes, Pseudobutyrivibrio, Clostridium, and Butyrivibrio (P = 0.021), after the probiotic intervention. In contrast, in participants with initial butyrate concentrations <25 mmol/kg of wet feces, the probiotic contributed to a 329 ± 255% (mean ± SD) increment in butyrate concomitantly with an ~55% decrease in Ruminococcus (P = 0.016) and a 150% increase in an abundantly represented unclassified Bacteroidales genus (P = 0.05). Conclusions: The intake of L. paracasei DG increased the Blautia:Coprococcus ratio, which, according to the literature, can potentially confer a health benefit on the host. The probiotic impact on themicrobiota and on short-chain fatty acids, however, seems to strictly depend on the initial characteristics of the intestinal microbial ecosystem. In particular, fecal butyrate concentrations could represent an important biomarker for identifying subjects who may benefit from probiotic treatment

Oral supplementation with sucrosomial ferric pyrophosphate plus L-ascorbic acid to ameliorate the martial status : a randomized controlled trial

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient's functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient's tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients ( 65 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost -2.8 \ub1 5.1%, while the intervention group gained +0.7 \ub1 4.6% of circulating hemoglobin from baseline (p = 0.019). Gastrointestinal diseases, medications, and possible dietary factors could affect the efficacy of iron supplements. Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level

"Nutrizione e Rischio Cardiovascolare"

Wild blueberries are rich sources of polyphenols such as anthocyanins capable of counteracting oxidative stress, influencing vasomotor tone and modulating gene expression associated with disease processes such as cardiovascular disease

Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis

The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture

Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors

PURPOSE: Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease. METHODS: Eighteen male volunteers (ages 47.8\ua0\ub1\ua09.7\ua0years; body mass index 24.8\ua0\ub1\ua02.6\ua0kg/m(2)) received according to a cross-over design, a WB (25\ua0g freeze-dried powder, providing 375\ua0mg of ACNs) or a PL drink for 6\ua0weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed. RESULTS: Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5\ua0\ub1\ua05.6\ua0% to 9.6\ua0\ub1\ua03.5\ua0%, p\ua0 64\ua00.01) and the levels of H(2)O(2)-induced DNA damage (from 45.8\ua0\ub1\ua07.9\ua0% to 37.2\ua0\ub1\ua09.1\ua0%, p\ua0 64\ua00.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study. CONCLUSIONS: In conclusion, the consumption of the WB drink for 6\ua0weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function