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We combined novel laboratory techniques and numerical modeling to investigate (a)seismic preparatory processes associated with deformation localization during a triaxial failure test on a dry sample of Berea sandstone. Laboratory observations were quantified by measuring strain localization on the sample surface with a distributed strain sensing (DSS) array, utilizing optical fibers, in conjunction with both passive and active acoustic emission (AE) techniques. A physics-based computational model was subsequently employed to understand the underlying physics of these observations and to establish a spatio-temporal correlation between the laboratory and modeling results. These simulations revealed three distinct stages of preparatory processes: (i) highly dissipative fronts propagated towards the middle of the sample correlating with the observed acoustic emission locations; (ii) dissipative regions were individuated in the middle of the sample and could be linked to a discernible decrease of the P-wave velocities; (iii) a system of conjugate bands formed, coalesced into a single band that grew from the center towards the sample surface and was interpreted to be representative for the preparation of a weak plane. Dilatative lobes at the process zones of the weak plane extended outwards and grew to the surface, causing strain localization and an acceleration of the simulated deformation prior to failure. This was also observed during the experiment with the strain rate measurements and spatio-temporally correlated with an increase of the seismicity rate in a similar rock volume. The combined approach of such laboratory and numerical techniques provides an enriched view of (a)seismic preparatory processes preceding the mainshock.

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Earthquakes are rupture-like processes that propagate along tectonic faults and cause seismic waves. The propagation speed and final area of the rupture, which determine an earthquake's potential impact, are directly related to the nature and quantity of the energy dissipation involved in the rupture process. Here, we present the challenges associated with defining and measuring the energy dissipation in laboratory and natural earthquakes across many scales. We discuss the importance and implications of distinguishing between energy dissipation that occurs close to and far behind the rupture tip, and we identify open scientific questions related to a consistent modeling framework for earthquake physics that extends beyond classical Linear Elastic Fracture Mechanics.

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BACKGROUND: Zinc-biofortified potatoes have considerable potential to reduce zinc deficiency because of their low levels of phytate, an inhibitor of zinc absorption, and their high consumption, especially in the Andean region of Peru. OBJECTIVES: The purpose of this study was to measure fractional and total zinc absorption from a test meal of biofortified compared with regular potatoes. METHODS: We undertook a single-blinded randomized crossover study (using 67Zn and 70Zn stable isotopes) in which 37 women consumed 500-g biofortified or regular potatoes twice a day. Urine samples were collected to determine fractional and total zinc absorption. RESULTS: The zinc content of the biofortified potato and regular potato was 0.48 (standard deviation [SD]: 0.02) and 0.32 (SD: 0.03) mg/100 g fresh weight, respectively. Mean fractional zinc absorption (FZA) from the biofortified potatoes was lower than from the regular potatoes, 20.8% (SD: 5.4%) and 25.5% (SD: 7.0%), respectively (P < 0.01). However, total zinc absorbed was significantly higher (0.49; SD: 0.13 and 0.40; SD: 0.11 mg/500 g, P < 0.01, respectively). CONCLUSIONS: The results of this study demonstrate that biofortified potatoes provide more absorbable zinc than regular potatoes. Zinc-biofortified potatoes could contribute toward reducing zinc deficiency in populations where potatoes are a staple food. This trial was registered at clinicaltrials.gov as NCT05154500.

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A polyphenol-rich diet reduced intestinal permeability (IP) in older adults. Our aim was to evaluate if participants categorized according to urolithin metabotypes (UMs) exhibited different responses in the MaPLE trial. Fifty-one older adults (mean age: 78 years) completed an 8-week randomized-controlled-crossover trial comparing the effects of a polyphenol-rich vs. a control diet on IP, assessed through zonulin levels. Plasma and urinary metabolomics were evaluated with a semi-targeted UHPLC-MS/MS method. Gut microbiota was characterized by 16S rRNA gene profiling. UMs were determined according to urolithin excretion in 24 h urine samples. Multivariate statistics were used to characterize the differences in metabolomic and metataxonomic responses across UMs. Thirty-three participants were classified as urolithin metabotype A (UMA), 13 as urolithin metabotype B (UMB), and 5 as urolithin metabotype 0 (UM0) according to their urinary excretion of urolithins. Clinical, dietary, and biochemical characteristics at baseline were similar between UMs (all p > 0.05). After the polyphenol-rich diet, UMB vs. UMA participants showed a 2-fold higher improvement of zonulin levels (p for interaction = 0.033). Moreover, UMB vs. UMA participants were characterized for alterations in fatty acid metabolism, kynurenine pathway of tryptophan catabolism, and microbial metabolization of phenolic acids. These changes were correlated with the reduction of zonulin levels and modifications of gut microbes (increased Clostridiales, including, R. lactaris, and G. formicilis). In conclusion, urolithin-based metabotyping identified older adults with a higher improvement of IP after a polyphenol-rich diet. Our results reinforce the concept that UMs may contribute to tailor personalized nutrition interventions.

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BACKGROUND &AIM: The MaPLE study was a randomized, controlled, crossover trial involving adults ≥60 y.o. (n = 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. Results from the MaPLE trial showed that the PR-diet reduced the intestinal permeability (IP) in older adults by inducing changes to gut microbiota (GM). The present work aimed at studying the changes in serum metabolome in the MaPLE trial, as a further necessary step to depict the complex crosstalk between dietary polyphenols, GM, and intestinal barrier. METHODS: Serum metabolome was monitored using a semi-targeted UHPLC-MS/MS analysis. Metataxonomic analysis (16S rRNA gene profiling) of GM was performed on faecal samples. Clinical characteristics and serum levels of the IP marker zonulin were linked to GM and metabolomics data in a multi-omics network. RESULTS: Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake. Theobromine and methylxanthines, derived from cocoa and/or green tea, were positively correlated with butyrate-producing bacteria (the order Clostridiales and the genera Roseburia, Butyricicoccus and Faecalibacterium) and inversely with zonulin. A direct correlation between polyphenol metabolites hydroxyphenylpropionic acid-sulfate, 2-methylpyrogallol-sulfate and catechol-sulfate with Butyricicoccus was also observed, while hydroxyphenylpropionic acid-sulfate and 2-methylpyrogallol-sulfate negatively correlated with Methanobrevibacter. The multi-omics network indicated that participant's age, baseline zonulin levels, and changes in Porphyromonadaceae abundance were the main factors driving the effects of a PR-diet on zonulin. CONCLUSION: Overall, these results reveal the complex relationships among polyphenols consumption, intestinal permeability, and GM composition in older adults, and they may be important when setting personalized dietary interventions for older adults. TRIAL REGISTRATION NUMBER: ISRCTN10214981.

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Slow slip events (SSEs) represent a slow faulting process leading to aseismic strain release often accompanied by seismic tremor or earthquake swarms. The larger SSEs last longer and are often associated with intense and energetic tremor activity, suggesting that aseismic slip controls tremor genesis. A similar pattern has been observed for SSEs that trigger earthquake swarms, although no comparative studies exist on the source parameters of SSEs and tremor or earthquake swarms. We analyze the source scaling of SSEs and associated tremor- or swarm-like seismicity through our newly compiled dataset. We find a correlation between the aseismic and seismic moment release indicating that the shallower SSEs produce larger seismic moment release than deeper SSEs. The scaling may arise from the heterogeneous frictional and rheological properties of faults prone to SSEs and is mainly controlled by temperature. Our results indicate that similar physical phenomena govern tremor and earthquake swarms during SSEs.

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Polyphenols have great potential in regulating intestinal health and ameliorating pathological conditions related to increased intestinal permeability (IP). However, the efficacy of dietary interventions with these phytochemicals may significantly be influenced by interindividual variability factors affecting their bioavailability and consequent biological activity. In the present study, urine samples collected from older subjects undergoing a crossover intervention trial with polyphenol-rich foods were subjected to metabolomics analysis for investigating the impact of increased IP on the bioavailability of polyphenols. Interestingly, urinary levels of phase II and microbiota-derived metabolites were significantly different between subjects with healthier intestinal barrier integrity and those with increased IP disruption. Our results support that this IP-dependent impaired bioavailability of polyphenols could be attributed to disturbances in the gut microbial metabolism and phase II methylation processes. Furthermore, we also observed that microbiota-derived metabolites could be largely responsible for the biological activity elicited by dietary polyphenols against age-related disrupted IP.

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The gut microbiota is involved in the regulation of the intestinal permeability (IP), whose disruption is a frequent condition in older people and is associated with the development of several diseases. The diet can affect the gut microbiota and IP, although the molecular mechanisms involved are unclear. Metabolomics is one of the suitable approaches to study the effects of diet on gut microbiota and IP, although, up to now, the research has focused only on a few dietary components. The aim here was to review the most recent literature concerning the application of metabolomics to the study of the diet-induced alterations of gut microbiota and the effects on IP, with a particular focus on the molecular pathways involved. An additional aim was to give a perspective on the future research involving dietary polyphenols, because despite their potential use in the management of increased IP, few studies have been reported to date.

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BACKGROUND: Physiotherapy treatment of frozen shoulder is varied, but most lack specific focus on the underlying disorder, which is the adhered shoulder capsule. Although positive effects were found after physiotherapy, the recurrence and prolonged disability of a frozen shoulder are major factors to focus on to provide the appropriate treatment. QUESTIONS/PURPOSES: We wished to study the effectiveness of a shoulder countertraction apparatus on ROM, pain, and function in patients with a frozen shoulder and compare their results with those of control subjects who received conventional physiotherapy. METHODS: A total of 100 participants were randomly assigned to an experimental group and a control group, with each group having 50 participants. The control group received physiotherapy and the experimental group received countertraction and physiotherapy. The total treatment time was 20 minutes a day for 5 days per week for 2 weeks. The outcome measures used were goniometer measurements, VAS, and the Oxford Shoulder Score. RESULTS: Improvements were seen in the scores for shoulder flexion (94.1° ± 19.79° at baseline increased to 161.9° ± 13.05° after intervention), abduction ROM (90.4° ± 21.18° at baseline increased to 154.8° ± 13.21° after intervention), and pain (8.00 ± 0.78 at baseline decreased to 3.48 ± 0.71 after intervention) in the experimental group. Sixty percent of the participants (n = 30) were improved to the fourth stage of satisfactory joint function according to the Oxford Shoulder Score in the experimental group compared with 18% (n = 9) in the control group (p < 0.001). CONCLUSIONS: Incorporating shoulder countertraction along with physiotherapy improves shoulder function compared with physiotherapy alone for the treatment of a frozen shoulder. Additional studies are needed focusing on this concept to increase the generalizability of the counter-traction apparatus in various groups. LEVEL OF EVIDENCE: Level II, prospective comparative study. See the Instructions for Authors for a complete description of levels of evidence.

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In the present study, we aimed to analyze the antinociceptive, immunomodulatory and antipyretic activities of nymphayol were investigated in wistar rats and mice. Antinociceptive effect was evaluated by acetic acid induced writhing, formalin induced paw licking and hot-plate tests. Immunomodulatory activity was assessed by neutrophil adhesion test, humoral response to sheep red blood cells, delayed-type hypersensitivity, phagocytic activity and cyclophosphamide induced myelosuppression. Antipyretic activity was evaluated by yeast induced hyperthermia in rats. Nymphayol produced signifi cant (p<0.05) antinociceptive activity in acetic acid induced writhing response and late phase of the formalin induced paw licking response. Pre-treatment with nymphayol (50 mg/kg, oral) evoked a signifi cant increase in neutrophil adhesion to nylon fi bres. The augmentation of humoral immune response to sheep red blood cells by nymphayol (50 mg/kg) was evidenced by increase in antibody titres in rats. Oral administration of nymphayol (50 mg/kg) to rats potentiated the delayed-type hypersensitivity reaction induced by sheep red blood cells. Treatment with nymphayol showed a signifi cant (p<0.05) reduction in pyrexia in rats. The results suggest that nymphayol possesses potent anti-nociceptive, immunomodulatory and antipyretic activities.

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A variety of metals have been used to replace the skeletal framework of human beings. Gamma titanium aluminide (gammaTiAl) has been recently developed as a prospective material for turbine applications. In this preliminary study, the potential of gammaTiAl as a biomaterial was evaluated using an in vivo rat model. Sprague-Dawley rats were implanted with gammaTiAl cylinders in the femur and observed for an experimental period lasting up to 180 days. The rats were sacrificed after periods of 45, 90 and 180 days. The femurs with the gammaTiAl implants were extracted and examined using scanning electron microscopy (SEM). Normal bone growth processes were observed as early as 45 days after gammaTiAl cylinder implantation. No signs of rejection of the implant metal were observed. In fact, a layered bone growth was observed on the implant metal surface. The bone-metal interface showed signs of tissue growth from original bone to the metal surface. gammaTiAl appears to elicit a normal bone tissue reaction and hence, has potential as a metallic implant material.

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BACKGROUND: Music played during endoscopic procedures may alleviate anxiety and improve patient acceptance of the procedure. A prospective randomized, controlled trial was undertaken to determine whether music decreases the requirement for midazolam during colonoscopy and makes the procedure more comfortable and acceptable. METHODS: Patients undergoing elective colonoscopy between October 2003 and February 2004 were randomized to either not listen to music (Group 1; n=40) or listen to music of their choice (Group 2; n=38) during the procedure. All patients received intravenous midazolam on demand in aliquots of 2 mg each. The dose of midazolam, duration of procedure, recovery time, pain and discomfort scores and willingness to undergo a repeat procedure using the same sedation protocol were compared. RESULTS: Patients in Group 2 received significantly less midazolam than those in Group 1 (p=0.007). The pain score was similar in the two groups, whereas discomfort score was lower in Group 2 (p=0.001). Patients in the two groups were equally likely to be willing for a repeat procedure. CONCLUSION: Listening to music during colonoscopy helps reduce the dose of sedative medications and decreases discomfort experienced during the procedure.

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