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Background & Aims: Milk-derived miR-148a-3p (miR-148a), which is abundant in breast milk, has been shown to be associated with the development of infants' intestines. Although it is well known that stress during lactation changes milk constituents in terms of lipid and protein, no studies have examined the influence of stress on miR-148a expression in breast milk. The objective of this study is to investigate the relationship between stress and miR-148a expression in milk, and to evaluate whether the changes in milk-derived miR-148a expression-caused by the mother's exposure to stress-influence intestinal ZO-1 expression in infants., Methods: The participants of this study were healthy Japanese women who were nursing. Psychological stress evaluation of the subjects was conducted using a short form of the Profile of Mood State Second Edition-Adult (POMS-2). Additionally, miR-148a expressions in restraint stressed nursing mice were investigated using quantitative real-time PCR. The levels of a tight junction protein zonula occludens-1 (ZO-1) and DNA methyltransferase 1 (DNMT1), which is a direct target of miR-148a, in ileum in neonatal mice breastfed by stressed nursing mice were investigated using Western blot. Furthermore, to investigate the influence of miR-148a on ZO-1 expression within the intestine, the levels of ZO-1 and DNMT1 in human intestinal epithelial Caco-2 cells with lentivirus-mediated miR-148a overexpression were evaluated., Results: A significantly negative correlation was observed between relative miR-148a expression in breast milk and the total mood disturbance T-score. Each T-score on negative mood subscales of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, and tension-anxiety was significantly negatively correlated with relative miR-148a expression in breast milk: a positive mood subscale vigor-activity T-score was significantly positively correlated with relative miR-148a expression in breast milk. A positive mood friendliness T-score, estimated separately from other scores, was significantly positively correlated with relative miR-148a expression in breast milk. Additionally, the relative expression of miR-148a in the milk obtained from stressed mice was significantly lower than that of control mice. The relative level of ZO-1 in ileum of neonatal mice nursed by stressed mice was significantly lower than that of neonatal mice nursed by control mice. Additionally, the relative level of DNMT1 in ileum of neonatal mice nursed by stressed mice was significantly higher than that of neonatal mice nursed by control mice. Furthermore, the relative level of ZO-1 in miR-148a-overexpressed Caco-2 cells was significantly higher than that in control cells. The relative level of DNMT1 in miR-148a-overexpressed Caco-2 cells was significantly lower than that in control cells., Conclusions: Mothers' exposure to stress during lactation may cause miR-148a expression in breast milk. Additionally, stressed-induced suppression of miR-148a expression in breast milk may cause a decrease in intestinal ZO-1 level via the increase in DNMT1 in infants' intestines. These observations are beneficial information for breastfeeding mothers and their families and perinatal medical professionals. Our findings encourage monitoring maternal psychological stress during lactation to promote breastfeeding and adequate infant nutrition., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Milk-derived microRNAs (miRNAs), including hsa-miR-148a-3p (miR-148a) and hsa-miR-125b-5p (miR-125b), have been shown to be beneficial to the gastrointestinal function in infants. Here, we investigated their expression during lactation in humans and determined whether the infant formulae available in Japan contain these miRNAs., Methods: Healthy Japanese women (n = 16) who gave birth vaginally or by cesarean section at the Teine Keijinkai Hospital between 1 September 2020, and 31 April 2021 were included in this study. Breast milk was collected by nurses on days 4 or 5 after delivery (hereinafter, transition milk) and on day 30 of postpartum (hereinafter, mature milk). The levels of miR-148a and miR-125b in breastmilk and six commercially available infant formulae were compared and evaluated using quantitative reverse transcription-polymerase chain reaction., Results: In all participants, the miR-148a level in mature breastmilk was significantly lower than that in the transition milk. The changes in miR-125b expression during lactation showed similar trends to the changes in miR-148a expression. The miR-148a and miR-125b levels in all analyzed infant formulae were lower than 1/500th and 1/100th of those in mature breastmilk, respectively., Conclusions: The levels of both miR-148a and miR-125b in human breast milk decreased on day 30 postpartum compared with those in the transition milk. Additionally, the expression of these miRNAs in infant formulae available in Japan was very low. Further studies with larger populations are required to understand precisely the lactational changes in the expression of miR148a and miR-125b in breast milk., (© 2021. The Author(s).)

Study Design: Prospective cohort study., Objective: To investigate the dynamic changes of cervical spinal cord with postural change after cervical laminoplasty by means of postoperative percutaneous ultrasonography., Summary of Background Data: Many reports have been published about intraoperative ultrasonographic evaluation of the spinal cord. Few reports have described postoperative diagnostic ultrasonographic findings of the spinal cord after a previous laminectomy. To date, there are no studies that have examined the changes in pulsation pattern and intensity of the spinal cord at different body positions with percutaneous ultrasonography., Methods: Thirty-three patients after cervical laminoplasty were evaluated postoperatively by percutaneous ultrasonography of the cervical spinal cord. Ultrasonographic images were obtained from 5 different body positions sitting with neck neutral, sitting with neck flexion, sitting with neck extension, prone, and supine position., Results: The pattern and intensity of cervical spinal cord pulsation and the anteroposterior position of the cervical spinal cord changed according to posture. Pulsation of the cervical spinal cord was more common in sitting position, whereas wave motion was more common in supine position.Supine, prone, sitting with neck extension, sitting with neck neutral, and sitting with neck flexion position were ranked in descending order of spinal cord pulsating intensity. Subarachnoidal space ventral to the cervical spinal cord was more likely to appear in the supine position., Conclusion: Assuming that good spinal cord pulsation represents good spinal circulation, these results suggest that the supine position will provide the most favorable condition for recovery of the cervical spinal cord.

Reactivation of hepatitis B involves the reappearance of active necroinflammatory liver disease after an inactive hepatitis B surface antigen (HBsAg) carrier state or resolved hepatitis B, occurring during or after immunosuppression therapy or chemotherapy. We prospectively investigated the reactivation rate for hepatitis B virus (HBV) DNA replication in cases of rheumatoid arthritis (RA) with resolved hepatitis B. HBV markers were evaluated in 428 RA patients. Patients with positive findings of HBsAg or HBV DNA at enrolment were excluded. The study population comprised 422 RA patients, with resolved hepatitis B diagnosed in 135 patients based on HBsAg-negative and antihepatitis B core antibody/antihepatitis B surface antibody-positive results. HBV DNA was measured every 3 months in this group, and if HBV DNA became positive after enrolment, measurement was repeated every month. HBV DNA became positive (≥3.64 log copies/mL) in 7 of 135 patients for 12 months. Use of biologic agents was significantly more frequent in patients who developed reactivation of HBV DNA replication (85.7%) than in patients who did not (36.0%, p = 0.008). Hazard ratios for use of biologic agents and etanercept were 10.9 (p = 0.008) and 6.9 (p = 0.001), respectively. RA patients with resolved hepatitis B need careful monitoring when receiving biologic agents, regardless of HBV DNA levels.

We present a rare case of spontaneous bilateral Achilles tendon rupture induced by levofloxacin, one of the fluoroquinolone antibiotics. A 76-year-old man was diagnosed with acute appendicitis and was commenced on oral levofloxacin 300 mg/day for 2 weeks. Seven days afterward he developed pain in both Achilles tendons, and at 14 days he developed swelling in the tendons. Four days later he felt a sharp, painful snap in both Achilles tendons while changing trousers. Both Achilles tendons ruptured completely at the mid-portion. There was no obvious underlying disease or pathophysiological factor causing fragility of his Achilles tendons. Despite the relatively large volume of case-based evidence, the pathophysiology of fluoroquinolone-induced tendinitis and tendon rupture is unclear. When tendinitis develops during fluoroquinolone therapy, the physician should consider the possible association between the fluoroquinolone and tendon rupture.

To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1beta) and interferon gamma (IFN-gamma) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-alpha and tumour necrosis factor alpha (TNF-alpha) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-beta) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.

Decaglycerol mono-oleate (DGMO), a type of food additive (a polyglycerol ester of fatty acids), was evaluated for its in vitro effect on reactive oxygen species (ROS) generation by human neutrophils using a luminol-dependent chemiluminescence assay. Neutrophils were isolated by the Histopaque-1077/1119 double density gradient technique. Opsonized zymosan (OZ) and phorbol 12-myristate 13-acetate (PMA) were employed as artificial stimuli. DGMO inhibited the chemiluminescence response of OZ-stimulated neutrophils by 58% (p < 0.01) at a concentration of 0.5 mg/mL. DGMO inhibited the PMA-induced chemiluminescence by 40% (p < 0.01) at a concentration of 0.01 mg/mL. The inhibition phenomena could not be attributed to light absorption by DGMO alone, because the percentage chemiluminescence in the presence of DGMO is lower than the percentage transmittance of DGMO at 425 nm. These results suggest that DGMO downregulates ROS generation by human neutrophils., (Copyright 1999 John Wiley & Sons, Ltd.)

This study examined the applicability of luminol-dependent chemiluminescence (CL) response of neutrophils to assess the degree of stress of spinal surgery by measuring the capacity of circulating neutrophils to produce reactive oxygen species and the levels of serum cytokines: interleukin(IL)-1beta, IL-6, IL-8, tumour necrosis factor (TNF)-alpha and granulocyte colony stimulating factor (G-CSF). Ten male patients underwent spinal surgery. Peripheral blood samples, collected before and after the operation and the next morning, were used for measuring the CL response of neutrophils stimulated with opsonized zymosan and measuring the levels of serum cytokines. The operative stress induced leukocytosis, particularly granulocytosis, and increased serum IL-6 and G-CSF significantly. However, there was no significant change in the luminol-dependent CL response of neutrophils or the levels of serum IL-1beta, IL-8 and TNF-alpha throughout the experimental period. These results suggest that, at least in the early postoperative period, operative stress does not prime the circulating neutrophils, and thus the CL response of neutrophils is not appropriate to assess the degree of stress of spinal surgery., (Copyright 1999 John Wiley & Sons, Ltd.)