Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug ...screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC
of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.
Purpose
To investigate the effects of full marathon running on intrinsic and extrinsic foot muscle damage and to determine the relationship with the height change of the longitudinal foot arch ...following full marathon completion.
Methods
Magnetic resonance imaging‐measured transverse relaxation time (T2) of the abductor hallucis (ABH), flexor digitorum brevis (FDB) and quadratus plantae (QP), flexor digitorum longus (FDL), tibialis posterior (TP), and flexor hallucis longus (FHL) from 22 collegiate runners were assessed before and 1, 3, and 8 days after full marathon running. The three‐dimensional foot posture of 10 of the 22 runners was further obtained using a foot scanner system before and 1, 3, and 8 days after the marathon.
Results
Marathon‐induced increases in T2 were observed in the QP, FDL, TP, and FHL 1 day after the marathon (+7.5%, +4.7%, +6.7%, and +5.9%, respectively), with the increased T2 of TP persisting until 3 days after the marathon (+4.6%). T2 changes of FDL and FHL from pre‐marathon to DAY 1 showed direct correlations with the corresponding change in the arch height ratio (r = 0.823, p = 0.003, and r = 0.658, p = 0.038).
Conclusion
The damage and recovery response from a full marathon differed among muscles; QP, FDL, TP, and FHL increased T2 after the marathon, whereas ABH and FDB did not. In addition, T2 changes in FDL and FHL and the arch height ratio change were correlated. Our results suggest that the extrinsic foot muscles could be more susceptible to damage than the intrinsic during marathon running.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Previous studies suggest that marathon running induces lower extremity muscle damage. This study aimed to examine inter- and intramuscular differences in hamstring muscle damage after a marathon ...using transverse relaxation time (T.sub.2 )-weighted magnetic resonance images (MRI). 20 healthy collegiate marathon runners (15 males) were recruited for this study. T.sub.2 -MRI was performed before (PRE) and at 1 (D1), 3 (D3), and 8 days (D8) after marathon, and the T.sub.2 values of each hamstring muscle at the distal, middle, and proximal sites were calculated. Results indicated that no significant intermuscular differences in T.sub.2 changes were observed and that, regardless of muscle, the T.sub.2 values of the distal and middle sites increased significantly at D1 and D3 and recovered at D8, although those values of the proximal site remained constant. T.sub.2 significantly increased at distal and middle sites of the biceps femoris long head on D1 (p = 0.030 and p = 0.004, respectively) and D3 (p = 0.007 and p = 0.041, respectively), distal biceps femoris short head on D1 (p = 0.036), distal semitendinosus on D1 (p = 0.047) and D3 (p = 0.010), middle semitendinosus on D1 (p = 0.005), and distal and middle sites of the semimembranosus on D1 (p = 0.008 and p = 0.040, respectively) and D3 (p = 0.002 and p = 0.018, respectively). These results suggest that the distal and middle sites of the hamstring muscles are more susceptible to damage induced by running a full marathon. Conditioning that focuses on the distal and middle sites of the hamstring muscles may be more useful in improving recovery strategies after prolonged running.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prolonged running results in lowering of the foot arch and a low arch is associated with subsequent chronic injuries. Foot posture alteration and recovery following a marathon run remain unknown. ...Therefore, the present study aimed to evaluate foot posture alteration following a full marathon run. The three-dimensional foot posture data of 11 collegiate runners were obtained using an optical foot scanner system before, and immediately, 1 day, 3 days, and 8 days after a full marathon. The navicular height and arch height ratio significantly decreased from before to immediately, 1 day, 3 days, and 8 days after the marathon (navicular height: before, 44.2 ± 5.0 mm; immediately after, 39.4 ± 5.5 mm; 1 day, 37.7 ± 6.2 mm; 3 days, 38.7 ± 5.5 mm; 8 days, 37.6 ± 5.7 mm; arch height ratio: before, 18.4 ± 1.9; immediately after, 16.5 ± 2.5; 1 day, 15.7 ± 2.5; 3 days, 16.2 ± 2.6; 8 days, 15.6 ± 2.2, P < 0.001, respectively). By contrast, the dorsal height significantly increased from before and immediately after to 1 day after the marathon, and then significantly decreased until 8 days after the marathon (P < 0.001). These results indicate that the recovery patterns of the dorsal and navicular heights following a marathon did not coincide; the dorsal height rose temporally at 1 day after and subsequently decreased, but the navicular height decreased throughout the 8-day period after the marathon. More than one week may be necessary for sufficient foot alignment recovery from marathon-induced changes.
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FSPLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Long-distance running results in lowering of the foot medial longitudinal arch, but it is unknown whether the left and right arches decrease equally. This study aimed to determine whether foot arch ...asymmetry increases upon completion of a full marathon and to identify factors capable of explaining the degree of asymmetry of navicular height and navicular height displacement. The three-dimensional foot posture data of 74 collegiate runners were obtained using an optical foot scanner system before (PRE) and immediately after (POST) a full marathon. The navicular height and arch height ratio (normalised navicular height by foot length) of both feet significantly decreased from PRE to POST full marathon completion (44.3 ± 6.3 mm versus 40.8 ± 6.5 mm, 17.8 ± 2.5 versus 16.6 ± 2.7, respectively; p < 0.001, both). The asymmetry of the arch height ratio was significantly greater POST than PRE marathon. Multiple linear regression analysis indicated that the POST-race Asymmetry Index (AI) of navicular height was significantly predicted by the PRE-race AI of navicular height; navicular height displacement was predicted by PRE-race navicular height and the marathon time. Full marathon running induced increasing asymmetry and lowering of the medial longitudinal arch in runners.
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BFBNIB, FSPLJ, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
PURPOSETreatment of sinonasal malignant tumors is challenging, and evidence to establish a standard treatment is limited. Our objective was to evaluate the efficacy and safety of spot scanning proton ...therapy (SSPT) for sinonasal malignant tumors. PATIENTS AND METHODSWe retrospectively analyzed patients with sinonasal malignant tumors (T1-4bN0-2M0) who underwent SSPT between May 2014 and September 2019. The prescription dose was typically either 60 GyRBE in 15 fractions or 60.8 GyRBE in 16 fractions for mucosal melanoma and 70.2 GyRBE in 26 fractions for other histologic subtypes. Endpoints included local control (LC), progression-free survival, overall survival (OS), and incidence of toxicity. Prognostic factors were analyzed using the Kaplan-Meier method and log-rank test. RESULTSOf 62 enrolled patients, the common histologic subtypes were mucosal melanoma (35%), squamous cell carcinoma (27%), adenoid cystic carcinoma (16%), and olfactory neuroblastoma (10%). Locally advanced stages were common (T3 in 42% and T4 in 53%). Treatment-naïve tumors and postsurgical recurrent tumors accounted for 73% and 27%, respectively. No patient had previous radiotherapy. The median follow-up was 17 months (range, 6-66) for all patients and 21.5 months (range, 6-66) for survivors. The 2-year LC, progression-free survival, and OS rates of all patients were 92%, 50%, and 76%, respectively. Univariate analysis revealed histology as a prognostic factor for OS, being higher in adenoid cystic carcinoma and olfactory neuroblastoma than in other tumors. Sixteen grade ≥3 late toxicities were observed in 12 patients (19%), including 11 events resulting in visual impairment; the most common was cataract. There was 1 grade 4 toxicity, and there were no grade 5 toxicities. CONCLUSIONSSPT was well tolerated and yielded good LC for sinonasal malignant tumors. Although we consider SSPT to be a leading treatment modality, further studies are required to establish its status as a standard treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The complication of diverticulitis in the patients with ulcerative colitis (UC) is rare, because UC is common in young people and diverticulosis in elderly people. Here we presented a rare case of UC ...with sigmoid colon stenosis due to the abscess derived from diverticulitis.70-year-old male with 2-year history of ulcerative colitis (UC) treated with 5-aminosalycilic acid (5-ASA) admitted to our hospital due to the recurrence after one-year remission. Blood examination demonstrated elevated white blood cell (WBC) and CRP. Contrast-enhanced computed tomography (CT) demonstrated abscess formation around sigmoid colon with multiple diverticulosis, and thickening of colonic wall from sigmoid colon to rectum. Colonoscopy demonstrated recurrence of UC and sigmoid colon stenosis. Prednisolone improved mucosal inflammation, however, did not improve stenosis and abscess formation. Therefore, sigmiodectomy was performed and resected specimen presented sigmoid colon stenosis with diverticulitis with the infiltration of neutrophils. Differential diagnosis may include superimpose of diverticular colitis in the setting of UC.Diverticulitis should be considered as differential diagnosis when segmental stenosis was complicated in elderly patients with UC.
要旨
...硫酸マグネシウム(以下Mg)静注療法は,破傷風の筋痙攣・強直や自律神経障害への有効性が報告されている。しかし,その投与量の調整方法は確立されていない。本邦で破傷風患者は稀であるが,我々は異なる指標で硫酸Mgの投与量を調整した2名の破傷風患者を経験した。患者1では臨床所見にもとづいて調整したところ,筋痙攣・強直や自律神経障害のコントロールは良好であったものの重篤な高Mg血症を生じ,経過中にQT延長と気管内出血の合併症を来した。患者2では血清Mg濃度で投与量を調整したところ,患者1よりも血圧変動が目立ったものの,有害事象を生じることなく良好な転帰を得ることができた。破傷風に対して硫酸Mg静注を行う際には,ある程度の自律神経障害が残存したとしても,重篤な高Mg血症を来さないように血中濃度をもとに投与量を調整するほうが好ましい可能性が示唆された。
ABSTRACT
Continuous intravenous magnesium (Mg) infusion is reported to be effective for improving muscle spasm, myotonia, and autonomic neuropathy, all of which pose problems in the systemic management of tetanus. However, much remains unknown regarding adverse events such as arrhythmia secondary to hypermagnesemia, and few studies have defined the ideal serum concentration of Mg. Through our experience with managing two cases of tetanus, which is a rare condition in Japan, we have examined the efficacy and safety of Mg. In Case 1, we managed serum Mg concentration based on clinical findings. Although we achieved favorable control of muscle spasm, myotonia, and autonomic neuropathy, the patient had a high serum concentration of Mg and showed QT prolongation and endotracheal bleeding secondary to hypermagnesemia as adverse events. In Case 2, we maintained the patient’s serum Mg concentration at 4.5−7.5mg/dL. The patient demonstrated greater variations in vital signs than in Case 1 but did not develop any adverse events associated with hypermagnesemia. Our experience suggests that, administering Mg until it completely suppresses muscle spasm, myotonia, and autonomic neuropathy may cause serious side effects due to hypermagemia, patients with tetanus can be managed more safely when serum concentrations of Mg are maintained within an appropriate range (4.5−7.5mg/dL).