Effect of quercetin glycosides on cognitive functions and cerebral blood flow: a randomized, double-blind, and placebo-controlled study.

OBJECTIVE: This study aimed to examine the effects of quercetin glycoside-containing beverages on cognitive function and cerebral blood flow (CBF) in adult men and women aged between 60 and 75 years. PATIENTS AND METHODS: Eighty healthy men and women with no cognitive impairment and aware of ageing-related forgetfulness underwent a placebo-controlled, randomized, double-blind, and parallel-group trial. They regularly consumed 500 mL of beverage containing 110 mg of quercetin glycoside as isoquercitrin for 40 weeks. Cognitive function assessment by Cognitrax was the endpoint of the study. The participants were assessed for CBF, health-related quality of life, as well as physical, biological, and hematological parameters, and lateral index. RESULTS: Cognitrax demonstrated that the reaction time significantly improved in the quercetin glycoside intake group. The CBF measurement suggested that quercetin glycoside intake could likely suppress the decrease in cerebral blood volume, CBF, and cerebral activity owing to stress alleviation and inhibition of the accumulation of amyloid ß (Aß), a waste product in the brain, although there were no significant differences between the groups. CONCLUSIONS: Quercetin glycoside intake as a beverage could improve reaction time and may potentially inhibit the decrease in CBF and suppress Aß accumulation.

Interpretable AI Explores Effective Components of CAD/CAM Resin Composites.

High flexural strength of computer-aided manufacturing resin composite blocks (CAD/CAM RCBs) are required in clinical scenarios. However, the conventional in vitro approach of modifying materials' composition by trial and error was not efficient to explore the effective components that contribute to the flexural strength. Machine learning (ML) is a powerful tool to achieve the above goals. Therefore, the aim of this study was to develop ML models to predict the flexural strength of CAD/CAM RCBs and explore the components that affect flexural strength as the first step. The composition of 12 commercially available products and flexural strength were collected from the manufacturers and literature. The initial data consisted of 16 attributes and 12 samples. Considering that the input data for each sample were recognized as a multidimensional vector, a fluctuation range of 0.1 was proposed for each vector and the number of samples was augmented to 120. Regression algorithms-that is, random forest (RF), extra trees, gradient boosting decision tree, light gradient boosting machine, and extreme gradient boosting-were used to develop 5 ML models to predict flexural strength. An exhaustive search and feature importance analysis were conducted to analyze the effective components that affected flexural strength. The R2 values for each model were 0.947, 0.997, 0.998, 0.983, and 0.927, respectively. The relative errors of all the algorithms were within 15%. Among the high predicted flexural strength group in the exhaustive search, urethane dimethacrylate was contained in all compositions. Filler content and triethylene glycol dimethacrylate were the top 2 features predicted by all models in the feature importance analysis. ZrSiO4 was the third important feature for all models, except the RF model. The ML models established in this study successfully predicted the flexural strength of CAD/CAM RCBs and identified the effective components that affected flexural strength based on the available data set.

Modified open posterior internal sphincterotomy with sliding skin graft for chronic anal fissure and anal stenosis: Low recurrence rate and no serious faecal incontinence postoperative complication.

AIM: Lateral internal sphincterotomy (LIS) remains a standard for chronic anal fissure even though other surgical techniques have shown high efficacy. Faecal incontinence is a well-documented complication of LIS. We devised modified open posterior internal sphincterotomy (m-OPIS) with sliding skin graft (SSG), which is a combined procedure of OPIS and anal advancement flap. The aim of this study is to evaluate m-OPIS+SSG. METHODS: This was a retrospective, observational, single-arm study. m-OPIS+SSG was performed for chronic anal fissure and anal stenosis. m-OPIS involved incision of the internal sphincter muscle at the posterior midline until four fingers could be passed. The incision wound was closed by anastomosis of the anoderm and skin. Then, an arcuate skin incision was created and the skin graft was advanced into the anal canal. Follow-up was conducted by clinical consultation and telephone interview. Faecal continence was assessed by Cleveland Clinic Faecal Incontinence (CCFI) score. RESULTS: m-OPIS+SSG was performed in 143 patients. The mean patient age was 50±16 years. The success and overall recurrence rates after m-OPIS+SSG were 99% and 0.7%, respectively, with a median follow-up period of 16.3 years. One patient developed incontinence with liquid stools once during the 6-month period. None of the other patients suffered permanent faecal incontinence postoperatively. The postoperative CCFI score was 0.5±0.9. CONCLUSIONS: We consider m-OPIS+SSG as one of the efficacious options of procedure for chronic anal fissure and anal stenosis, owing to its high success rate, low recurrence rate and no postoperative complication of serious faecal incontinence.

Ultrafast Creation of Overlapping Rydberg Electrons in an Atomic BEC and Mott-Insulator Lattice.

We study an array of ultracold atoms in an optical lattice (Mott insulator) excited with a coherent ultrashort laser pulse to a state where single-electron wave functions spatially overlap. Beyond a threshold principal quantum number where Rydberg orbitals of neighboring lattice sites overlap with each other, the atoms efficiently undergo spontaneous Penning ionization resulting in a drastic change of ion-counting statistics, sharp increase of avalanche ionization, and the formation of an ultracold plasma. These observations signal the actual creation of electronic states with overlapping wave functions, which is further confirmed by a significant difference in ionization dynamics between a Bose-Einstein condensate and a Mott insulator. This system is a promising platform for simulating electronic many-body phenomena dominated by Coulomb interactions in the condensed phase.

Comparison of early femoral bone remodeling and functional outcome after total hip arthroplasty using the SL-PLUS MIA stem with and without hydroxyapatite coating.

BACKGROUND: Few reports have evaluated the use of hydroxyapatite (HA) coating in SL-MIA-type stems in total hip arthroplasty (THA). Here, we compared early femoral bone remodeling after total hip arthroplasty using the SL-PLUS MIA stem with and without hydroxyapatite coating. METHODS: From February 2012 to March 2017, 132 patients (150 hips) (HA group: 48 patients [52 hips], non-HA group: 84 patients [98 hips]) underwent THA with an SL-PLUS MIA stem. The mean follow-up duration was 3.7 years (standard deviation 1.2, range: 1.0-6.1). The Harris Hip Score (HHS), postoperative bleeding volume measurements and plain radiographs were used for clinical and radiological follow-up evaluations. Peri-prosthetic bone mineral density changes were measured by dual-energy X-ray absorptiometry. RESULTS: At 1 year, the HHS improved from 44.4 points preoperatively to 89.2 points postoperatively and from 44.5 points to 89.7 points in the HA and non-HA groups, respectively. At 1 year postoperatively, subsidence (≧ 3 mm) occurred in 0% and 8.2% of the HA and non-HA groups, respectively. Stress shielding (≧ Grade 3) occurred in 0% and 6% of the HA and non-HA groups, respectively. The radiolucent line was significantly smaller in the HA than in the non-HA group. There was no significant difference in the bone mineral density distribution in the two groups. CONCLUSION: Addition of HA to the SL-MIA stem can help enhance the initial fixation and early osseointegration. Further studies are required on the long-term effects of adding HA to reduce stress shielding of the proximal area of the stem.

Addition of low-dose liraglutide to insulin therapy is useful for glycaemic control during the peri-operative period: effect of glucagon-like peptide-1 receptor agonist therapy on glycaemic control in patients undergoing cardiac surgery (GLOLIA study).

AIM: To test the hypothesis that the addition of a glucagon-like peptide-1 receptor agonist that can decrease glucose levels without increasing the hypoglycaemia risk will achieve appropriate glycaemic control during the peri-operative period. METHODS: We studied 70 people with Type 2 diabetes who underwent elective cardiac surgery. Participants were randomized to either an insulin-alone or an insulin plus liraglutide 0.6 mg/day group. We evaluated average M values, which indicated the proximity index of the target glucose level from day 1 to day 10. RESULTS: The average M value in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (liraglutide plus insulin 5.8 vs insulin-alone 12.3; P < 0.001). The frequency of insulin dose modification in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (odds ratio 0.19, 95% CI 0.08-0.49; P < 0.001). The frequency of hypoglycaemia in the liraglutide plus insulin group tended to be lower than that in the insulin-alone group (odds ratio 0.57, 95% CI 0.15-2.23; P = 0.21). CONCLUSIONS: The results of this study showed that the addition of low-dose liraglutide to insulin achieved lower M values than insulin alone, suggesting that the addition of low-dose liraglutide may achieve better glycaemic control during the peri-operative period. (Clinical trials registry no.: UMIN 000008003).

Serum high-mobility group box 1 is correlated with interferon-α and may predict disease activity in patients with systemic lupus erythematosus.

Sensing self-nucleic acids through toll-like receptors in plasmacytoid dendritic cells (pDCs), and the dysregulated type I IFN production, represent pathogenic events in the development of the autoimmune responses in systemic lupus erythematosus (SLE). Production of high-mobility group box-1 protein (HMGB1) promotes type I IFN response in pDCs. To better understand the active pathogenic mechanism of SLE, we measured serum levels of HMGB1, thrombomodulin, and cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, IFNα, IFNγ, TNFα) in 35 patients with SLE. Serum HMGB1 and IFNα were significantly higher in patients with active SLE (SLE Disease Activity Index (SLEDAI) score ≥ 6) compared with healthy donors or patients with inactive SLE. Furthermore, the HMGB1 levels were significantly correlated with IFNα levels. By qualitative analysis, the detection of serum IFNα or HMGB1 suggests active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels are biomarkers reflecting disease activity, and qualitative analysis of IFNα or HMGB1 is a useful screening test to estimate SLE severity and manifestations. Our results suggest the clinical significance of type I IFNs and HMGB1 as key molecules promoting the autoimmune process in SLE.

Bifidobacterium breve MCC1274 with glycosidic activity enhances in vivo isoflavone bioavailability.

Polyphenols are plant derived compounds that exert many beneficial health effects to the human host. However, associated health benefits of dietary polyphenol are highly dependent on their intestinal metabolism, bioavailability, and absorption. Bifidobacteria, which represent the key members of gut microbiota, have been suggested to promote gut microbial homeostasis and may be involved in the metabolism of polyphenols. In this study, the capabilities of thirteen Bifidobacterium strains in hydrolysing polyphenol glycosides were evaluated. Among the tested strains, Bifidobacterium breve MCC1274 was found to possess the highest ß-glucosidase activity and strong capability to convert daidzin and trans-polydatin to their aglycones; while kinetic analysis revealed that B. breve MCC1274 hydrolysed more than 50% of daidzin and trans-polydatin at less than 3 h of incubation. Further investigation using rats with an antibiotics-disturbed microbiome revealed that following the ingestion of daidzin glycoside, oral administration of B. breve MCC1274 significantly enhanced the plasma concentration of daidzein in rats pre-treated with antibiotics as compared to antibiotics-pre-treated control and non-treated control groups. The relative abundance of Actinobacteria and the total numbers of B. breve were also significantly higher in antibiotics-pre-treated rats administered with B. breve MCC1274 than that of the control groups. These findings suggest that B. breve MCC1274 is effective in enhancing the bioavailability of daidzein in the gut under dysbiosis conditions and may potentially improve intestinal absorption of isoflavones and promote human health.

Novel pseudo-aspartic peptidase from the midgut of the tick Rhipicephalus microplus.

The characterization of Rhipicephalus microplus tick physiology can support efforts to develop and improve the efficiency of control methods. A sequence containing a domain with similarity to one derived from the aspartic peptidase family was isolated from the midgut of engorged female R. microplus. The lack of the second catalytic aspartic acid residue suggest that it may be a pseudo-aspartic peptidase, and it was named RmPAP. In this work we confirm the lack of proteolytic activity of RmPAP and investigate it's non-proteolytic interaction with bovine hemoglobin by Surface Plasmon Resonance and phage display. Moreover we carried out RNAi interference and artificial feeding of ticks with anti-RmPAP antibodies to assess it's possible biological role, although no changes were observed in the biological parameters evaluated. Overall, we hypothesize that RmPAP may act as a carrier of hemoglobin/heme between the tick midgut and the ovaries.

Pathogen infections and primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a multi-factorial disease caused by the interaction of both genetic predisposition and environmental triggers. Bacterial infection has been investigated most intensively, both epidemiologically and experimentally, as a prime environmental aetiology in PBC. The association of recurrent history of urinary tract infection (UTI) with PBC has been frequently confirmed by several large-scale, case-control studies, despite variation in geographic area or case-finding methods. Escherichia coli is a predominant pathogen in most cases with UTI. Animal studies and molecular mimicry analysis between the human and E. coli E2 subunit of the 2-oxo-acid dehydrogenase complexes demonstrated that E. coli infection is a key factor in breaking immunological tolerance against the mitochondria, resulting in the production of anti-mitochondrial autoantibodies (AMA), the disease-specific autoantibodies of PBC. Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium, is another candidate which may be involved in the aetiology of PBC. Meanwhile, improved environmental hygiene and increased prevalence of PBC, especially in males, may argue against the aetiological role of bacterial infection in PBC. Multiple mechanisms can result in the loss of tolerance to mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably one of the dominant pathways, especially in female patients. Notably, there is a rising prevalence of male patients with PBC. With increasing exposure to environmental xenobiotics in both genders, studies directed towards identifying the environmental culprit with systematically designed case-control studies are much needed to further determine the environmental factors and role of bacterial infections in PBC.

Complex strain evolution of polar and magnetic order in multiferroic BiFeO3 thin films.

Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO3 and EuTiO3. Despite this critical need, there are few studies on the strain evolution of magnetic order in BiFeO3 films. Here, in (110)-oriented BiFeO3 films, we reveal that while the polarization structure remains relatively unaffected, strain can continuously tune the orientation of the antiferromagnetic-spin axis across a wide angular space, resulting in an unexpected deviation of the classical perpendicular relationship between the antiferromagnetic axis and the polarization. Calculations suggest that this evolution arises from a competition between the Dzyaloshinskii-Moriya interaction and single-ion anisotropy wherein the former dominates at small strains and the two are comparable at large strains. Finally, strong coupling between the BiFeO3 and the ferromagnet Co0.9Fe0.1 exists such that the magnetic anisotropy of the ferromagnet can be effectively controlled by engineering the orientation of the antiferromagnetic-spin axis.

Reduction in the colonization of Staphylococcus aureus on the skin surface under calcium-/magnesium-depleted conditions.

Excessive expansion of Staphylococcus aureus is associated with several skin diseases, including atopic dermatitis (AD). Recently, we have demonstrated that washing skins with ultra-pure soft water containing little bivalent metal ions improved skin conditions of atopic subjects. In this study, we investigated the roles of calcium or magnesium on the proliferation of S. aureus both in vitro and in vivo. Depletion of calcium and magnesium in the culture medium significantly suppressed the expansion of S. aureus growth. When S. aureus, diluted with water containing calcium/magnesium at the concentration of medium-hard water (83·0 mg l-1 as CaCO3 ) or the one that contains little calcium/magnesium, was applied onto the tape-stripped skin of Hos:HR-1 mice, growth of S. aureus in water without those minerals on the skin was suppressed. These results suggest that depletion of both calcium and magnesium abrogate the proliferation of S. aureus not only in the culture system but also on the skin surface of mice. Since colonization of S. aureus on the skin is well-known to exacerbate AD symptoms, usage of ultra-pure soft water containing less calcium and magnesium may improve the skin condition through the suppression of S. aureus growth on the skin of patients with skin problems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the importance of calcium and magnesium for the colonization and growth of Staphylococcus aureus by using both in vitro culture systems and in vivo experiments on the murine skin. Our results indicate that the removal of these metal ions is probably beneficial for protecting the skin from S. aureus. Thus, using ultra-pure soft water without metal ions may improve the skin condition of patients with skin problems through the protection from S. aureus colonization.

A two centre observational study of simultaneous pulse oximetry and arterial oxygen saturation recordings in intensive care unit patients.

The influence of variables that might affect the accuracy of pulse oximetry (SpO2) recordings in critically ill patients is not well established. We sought to describe the relationship between paired SpO2/SaO2 (oxygen saturation via arterial blood gas analysis) in adult intensive care unit (ICU) patients and to describe the diagnostic performance of SpO2 in detecting low SaO2 and PaO2. A paired SpO2/SaO2 measurement was obtained from 404 adults in ICU. Measurements were used to calculate bias, precision, and limits of agreement. Associations between bias and variables including vasopressor and inotrope use, capillary refill time, hand temperature, pulse pressure, body temperature, oximeter model, and skin colour were estimated. There was no overall statistically significant bias in paired SpO2/SaO2 measurements; observed limits of agreement were +/-4.4%. However, body temperature, oximeter model, and skin colour, were statistically significantly associated with the degree of bias. SpO2 <89% had a sensitivity of 3/7 (42.9%; 95% confidence intervals, CI, 9.9% to 81.6%) and a specificity of 344/384 (89.6%; 95% CI 86.1% to 92.5%) for detecting SaO2 <89%. The absence of statistically significant bias in paired SpO2/SaO2 in adult ICU patients provides support for the use of pulse oximetry to titrate oxygen therapy. However, SpO2 recordings alone should be used cautiously when SaO2 recordings of 4.4% higher or lower than the observed SpO2 would be of concern. A range of variables relevant to the critically ill had little or no effect on bias.

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan.

Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision-analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state-transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all-oral direct-acting anti-virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan-specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality-adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness-to-pay threshold of ¥4-to-¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment-related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness-to-pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness-to-pay thresholds. In conclusion treatment of HCV GT1b with all-oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.