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Insufficient suprahyoid muscle strength with poor opening of the upper esophageal sphincter can cause dysphagia. This study investigated whether an exercise of the suprahyoid muscle, named forehead exercise for suprahyoid muscles (FESM, “Enge-Odeko-Taiso” in Japanese), improves the geniohyoid muscle area and intensity using ultrasonography. Sixty-four participants (15 men and 49 women, 82.8 ± 6.0 years) living independently with no symptoms of swallowing difficulties were enrolled. The participants were divided into the FESM and the control group. The FESM is an isometric exercise involving repetitions of looking into the navel as if the chin is pulled back with little neck motion using a hand pushed against the forehead for resistance. This exercise is performed five times in 10 courses a day (total 50 times) for 8 weeks. Participants in the control group did not conduct any exercises. Body mass index, hand grip strength, gait speed, calf circumference, Mini Nutritional Assessment short-form, eating assessment tool, repetitive saliva swallowing test (RSST), and Food Intake LEVEL Scale scores were examined. The ultrasonographic geniohyoid muscle area, intensity, and RSST were investigated before and after the program. In the FESM group, the geniohyoid muscle area increased from 2.24 to 2.52 cm2 (P < 0.05), intensity decreased from 34.6 to 32.0 (P < 0.05), and the median RSST increased from 5 to 6 (P < 0.05) significantly. Conversely, no significant differences were observed in the control group. The FESM was effective to increase the area and decrease the intensity of the geniohyoid muscle and may improve swallowing function.

Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α -glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α -glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC 50 values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC 50 value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α -glucosidase inhibitory activity displaying IC 50 values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC 50 value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC 50 values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC 50 value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α -glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.

Key enzyme in vitamin K metabolism Vitamin K, an important factor in blood clotting and bone metabolism, is present in the diet principally as phylloquinone (PK) from plants. One form of the vitamin, menaquinone-4 or MK-4, has a highly specific tissue distribution in the brain, kidney and pancreas in humans and in rats, suggestive of local synthesis from phylloquinone. An enzyme catalysing that synthesis has now been identified: UbiA prenyltransferase containing 1 (UBIAD1) is a human homologue of an Escherichia coli enzyme. Previously its function was unclear, although it is a candidate gene in Schnyder crystalline corneal dystrophy. The discovery of a human MK-4 enzyme able to biosynthesize the hormonally active form of vitamin K is of relevance to work on human vitamin K requirements and bone health. These authors identify the human enzyme responsible for menaquinone-4 biosynthesis, a naturally occurring form of vitamin K. They find that UbiA prenyltransferase containing 1 , a human homologue of a prenyltransferase gene from Escherichia coli , encodes an enzyme that can convert vitamin K derivatives into menaquinone-4. Vitamin K occurs in the natural world in several forms, including a plant form, phylloquinone (PK), and a bacterial form, menaquinones (MKs). In many species, including humans, PK is a minor constituent of hepatic vitamin K content, with most hepatic vitamin K content comprising long-chain MKs. Menaquinone-4 (MK-4) is ubiquitously present in extrahepatic tissues, with particularly high concentrations in the brain, kidney and pancreas of humans and rats 1 , 2 , 3 . It has consistently been shown that PK is endogenously converted to MK-4 (refs 4–8 ). This occurs either directly within certain tissues or by interconversion to menadione (K 3 ), followed by prenylation to MK-4 (refs 9–12 ). No previous study has sought to identify the human enzyme responsible for MK-4 biosynthesis. Previously we provided evidence for the conversion of PK and K 3 into MK-4 in mouse cerebra 13 . However, the molecular mechanisms for these conversion reactions are unclear. Here we identify a human MK-4 biosynthetic enzyme. We screened the human genome database for prenylation enzymes and found UbiA prenyltransferase containing 1 ( UBIAD1 ), a human homologue of Escherichia coli prenyltransferase menA . We found that short interfering RNA against the UBIAD1 gene inhibited the conversion of deuterium-labelled vitamin K derivatives into deuterium-labelled-MK-4 (MK-4-d 7 ) in human cells. We confirmed that the UBIAD1 gene encodes an MK-4 biosynthetic enzyme through its expression and conversion of deuterium-labelled vitamin K derivatives into MK-4-d 7 in insect cells infected with UBIAD1 baculovirus. Converted MK-4-d 7 was chemically identified by 2 H-NMR analysis. MK-4 biosynthesis by UBIAD1 was not affected by the vitamin K antagonist warfarin. UBIAD1 was localized in endoplasmic reticulum and ubiquitously expressed in several tissues of mice. Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin K intake and bone health.

Background Aspiration pneumonia is a serious problem among elderly patients; it is caused by many risk factors including dysphagia, poor oral hygiene, malnutrition, and sedative medications. The aim of this study was to define a convenient procedure to objectively evaluate the risk of aspiration pneumonia in the clinical setting. Methods This prospective study included an aspiration pneumonia (AP) group, a community-acquired pneumonia (CAP) group, and a control (Con) group (patients hospitalized for lung cancer chemotherapy). We used the Oral Health Assessment Tool (OHAT), which assesses oral hygiene, and evaluated performance status, body mass index, serum albumin levels, substance P values in plasma, and oral bacterial counts. Results The oral health as assessed by the OHAT of the aspiration pneumonia group was significantly impaired compared with that of the CAP group and the control (5.13 ± 0.18, 4.40 ± 0.26, 3.90 ± 0.22, respectively; p  < 0.05). The oral bacterial count in the aspiration pneumonia group (7.20 ± 0.11) was significantly higher than that in the CAP group (6.89 ± 0.12), consistent with the OHAT scores. Oral bacterial count was significantly reduced by oral care. Conclusions OHAT and oral bacterial counts can be a tool to assess the requirement of taking oral care and other preventive procedures in patients at high risk of aspiration pneumonia.

This study aimed to analyze the posture patterns of surgeons with two different skill levels during laparoscopic surgery using an optical motion capture system. Twenty participants were divided into novice and expert groups. Their upper body motions during suturing tasks were captured, including average angle and angle variability (shoulder, elbow, wrist), joint fixation, head movement, and thoracolumbar flexion angle. Our analysis showed that (1) the arms of the expert surgeons were more loosely held at their sides by about 7°; (2) their elbows were more bent by about 10°; (3) they had a greater change in shoulder angle by about 1.4 times and a more fluid posture; (4) their heads were more stable, particularly in the longitudinal and vertical axes; and (5) their thoracolumbar flexion angle was smaller by about 10°. The posture patterns of different technical level surgeons during laparoscopic suturing maneuvers revealed differences in limb positions. These results may provide new insights into the efficient acquisition of technical skills and reduced physical stress during laparoscopic surgery. •We revealed the posture patterns of surgeons during laparoscopic suturing task.•Features of limb positioning for the expert group versus the novice group were:•Their arms were more loosely held to their sides, and their elbows were more bent.•They maintained a relatively fluid posture in the upper arm.•Their heads were more stable, and they tended not to be in a forward-leaning posture.

IntroductionVaccinations are ideal for reducing the severity of clinical manifestations and secondary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, SARS-CoV-2 continues to cause morbidity and mortality worldwide. In contrast to parenteral vaccines such as messenger RNA vaccines, nasal vaccines are expected to be more effective in preventing viral infections in the upper respiratory tract, the primary locus for viral infection and transmission. In this study, we examined the prospects of an inactivated whole-virion (WV) vaccine administered intranasally against SARS-CoV-2.MethodsMice were immunized subcutaneously (subcutaneous vaccine) or intranasally (nasal vaccine) with the inactivated WV of SARS-CoV-2 as the antigen.ResultsThe spike protein (S)-specific IgA level was found to be higher upon nasal vaccination than after subcutaneous vaccination. The level of S-specific IgG in the serum was also increased by the nasal vaccine, although it was lower than that induced by the subcutaneous vaccine. The nasal vaccine exhibited a stronger defense against viral invasion in the upper respiratory tract than the subcutaneous vaccine and unimmunized control; however, both subcutaneous and nasal vaccines provided protection in the lower respiratory tract. Furthermore, we found that intranasally administered inactivated WV elicited robust production of S-specific IgA in the nasal mucosa and IgG in the blood of mice previously vaccinated with messenger RNA encoding the S protein.DiscussionOverall, these results suggest that a nasal vaccine containing inactivated WV can be a highly effective means of protection against SARS-CoV-2 infection.

Background In pulmonary Mycobacterium avium complex (MAC) disease, serum cytokine profiles may offer insights into the immune responses underlying cavitary lesion development. We aimed to compare serum cytokine profiles between patients with cavitary and those with non-cavitary nodular bronchiectasis (NB) and to identify cytokines potentially associated with cavitary lung lesions. Methods This single-center, cross-sectional study included patients with pulmonary MAC disease presenting with NB, categorized into the cavitary and non-cavitary groups. The serum levels of 34 exploratory cytokines were measured using the MAGPIX system and enzyme-linked immunosorbent assays. Intergroup comparisons were subsequently performed. Results Nine and 45 patients with cavitary and non-cavitary NB MAC, respectively, were included. Significantly higher levels of interleukin (IL)-6 and IL-8/C-X-C motif chemokine ligand 8 (inflammatory markers), matrix metalloproteinase-8 and chitinase-3-like protein 1 (tissue remodeling factors), and IL-17E/IL-25 and suppression of tumorigenicity 2/IL-33R (T-helper type 2-related cytokines) were observed in the cavitary group. No significant differences were identified for the remaining cytokines. Conclusions Cavitary lung lesions in pulmonary MAC disease are associated with elevated levels of inflammatory markers, tissue remodeling factors, and T-helper type 2 related cytokines. Future research should investigate whether these cytokine differences contribute to cavity formation or occur as a consequence, and explore their potential as therapeutic targets.

Background Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. Methods This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. Results High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H 2 O 2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /μl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. Conclusions High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.

Spindle-shaped stromal cells of tumors are derived from various cellular origins, including mesenchymal stem cells (MSCs). MSCs express CD73, CD90 and CD105 antigens. Herein, the aim was to investigate the association between the expression of specific MSC markers in gastric cancer stromal cells and the clinicopathological features of the disease. The expression of CD73, CD90 and CD105 in spindle-shaped cancer stromal cells was studied by immunohistochemistry in tissue arrays containing 546 gastric cancer cases. Univariate and multivariate analyses were performed to evaluate the association of MSC marker expression with clinicopathological variables. Spindle-shaped cancer stromal cells expressing the MSC markers CD73, CD90 or CD105 were associated with larger tumor size, advanced cancer, venous infiltration, lymphatic infiltration, and lymph node metastasis. Statistical analysis demonstrated that the presence of CD105-positive spindle cells was an independent prognostic factor of advanced cancer, lymph node metastasis and EBV infection in multivariate analysis. Spindle-shaped gastric cancer stromal cells expressing CD73, CD90 or CD105 are involved in disease progression, and among them, CD105-positive cells are strongly associated with poor prognosis.

Several recent experimental studies have investigated the effects of caffeine and chlorogenic acid (CGA), representative ingredients of coffee, on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the results are conflicting, and their effects are yet to be clarified. In the present study, we examined the effects of caffeine and CGA on choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, relatively new model mice of NASH. Seven-week-old male C57BL/6J mice were divided into the following groups: Control diet (control), CDAHFD (CDAHFD), CDAHFD supplemented with 0.05% (w/w) caffeine (caffeine), and CDAHFD supplemented with 0.1% (w/w) CGA (CGA). After seven weeks, the mice were killed and serum biochemical, histopathological, and molecular analyses were performed. Serum alanine aminotransferase (ALT) levels were significantly higher in the caffeine and CGA groups than in the CDAHFD group. On image analysis, the prevalence of Oil red O-positive areas (reflecting steatosis) was significantly higher in the caffeine group than in the CDAHFD group, and that of CD45R-positive areas (reflecting lymphocytic infiltration) in the hepatic lobule was significantly higher in the caffeine and CGA groups than in the CDAHFD group. Hepatic expression of interleukin (IL)-6 mRNA was higher in the caffeine and CGA groups than in the CDAHFD group, and the difference was statistically significant for the caffeine group. In conclusion, in the present study, caffeine and CGA significantly worsened the markers of liver cell injury, inflammation, and/or steatosis in NASH lesions in mice.