Evaluation of planned number of children, the well-being of the couple and associated factors in a prospective cohort in Yokohama (HAMA study): study protocol.

INTRODUCTION: Many developed countries including Japan are experiencing declining birth rates, particularly in urban areas. A gap between the planned number of children and the actual number of children exists, that is attributed to various factors such as: childcare leave and employment policies, childcare services, financial support, husbands' contributions to household chores and childcare, marriage support, community, and couples' well-being. Therefore, we propose HAMA study for having a baby, parenting, and marriage life (HAMA = 'H'aving 'A' baby, parenting, and 'MA'rriage life) in Yokohama (an urban area) to examine these issues. METHODS AND ANALYSIS: In this large-scale cohort study, we will elucidate the actual situation of families and child-rearing in Yokohama, evaluate the current policies and propose future measures to prevent a decline in the birth rate. Overall, 10 000 young married couples (wives aged 20-39 years as of 2022) will be randomly selected, and a survey form will be sent to them annually. They will be followed-up for 5 years to examine the factors associated with the planned number of children, well-being of the couple, childcare support policies, externalisation of housework and childcare, fathers' participation in housework and childcare, wives' free time, loneliness and social connectedness, relationship with the spouse and if they are working, questions regarding their work style and work-life balance will also be included. Ultimately, a conceptual model of the planned number of children and associated factors will be developed. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Yokohama City University (reference number: 2022-10) and will be conducted following appropriate ethical guidelines. Opportunities to withdraw consent to participate in the survey are provided to participants. The results of this survey will be published as research papers in relevant journals and will be reported to the administration of Yokohama city and other agencies.

Effects of tongue right positioner use on tongue pressure: a pilot study.

The effectiveness of the tongue right positioner (TRP) use on oral and swallowing functions remains unclear. To investigate the effects of TRP use on tongue function in patients with dysphagia. This interventional study included eight participants with dysphagia who visited a university dental hospital. The measurement variables included tongue pressure (TP) as the primary outcome and lip and tongue movements, peak nasal inspiratory flow, and changes in the tongue and suprahyoid muscle regions on ultrasonography as the secondary outcomes. Each participant was asked to use a TRP for at least 8 h every night for 2 months. The measurement variables before and after the intervention were compared using the paired t test and Wilcoxon signed-rank test. TP after intervention (31.5 ± 13.1 kPa) was significantly higher than that before intervention (23.0 ± 13.4 kPa), while other measurement variables did not significantly improve. Numerous exercises have been suggested to improve TP; however, most require patients' adherence to instructions. In contrast, although participants did not perform active exercises, most participants in this study observed an improved TP. Our findings show that TRP can greatly improve TP after 2 months of usage.Trial registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN000040253, date of first registration: 27/04/2020).

Fib-4 index predicts prognosis after achievement of sustained virologic response following direct-acting antiviral treatment in patients with hepatitis C virus infection.

OBJECTIVES: Toinvestigate liver carcinogenesis and other causes of death by collecting clinical data, including the Fib-4 index, from patients with successfully eradicated hepatitis C virus (HCV) by direct-acting antivirals (DAA) treatment. METHODS: Patients ( n = 690), who achieved a sustained virologic response (SVR) between 2014 and 2021, were identified and followed up for approximately 6.8 years; 71 incident hepatocellular carcinoma (HCC) cases were identified. The Fib-4 index was calculated at DAA-treatment initiation and HCV eradication, and its relationship with carcinogenesis and prognosis was analyzed. RESULTS: The Fib-4 index was initially calculated and divided into three groups: Fib-4<1.45, 1.45 ≤ Fib-4<3.25, and 3.25 ≤ Fib-4 to develop HCC over time. On analysis, no carcinogenic cases were observed at Fib-4<1.45. In patients with a Fib-4 index ≥3.25, the initial HCC carcinogenic rate was higher than that in patients with Fib-4=1.45-3.25, and a significant difference was obtained between the two groups [ P = 0.0057 (<1.45 vs. >3.25); P = 0.0004 (<1.45-3.25 vs. >3.25)]. Regarding all 18 death and Fib-4 at treatment initiation, a significant difference was observed after stratification into two groups [Fib-4 < 3.25 and 3.25 ≤ Fib-4; P = 0.0136 (<3.25 vs. ≥3.25)]. Significant differences were obtained in another analysis of 13 deaths, not due to HCC. CONCLUSIONS: The high Fib-4 index calculated at baseline and SVR12 significantly correlated not only with liver carcinogenesis but also with all mortality rates, including those due to causes other than liver cancer. Our findings suggest that improving liver fibrosis by eradicating HCV improves prognosis related to all etiologies.

Measuring the quality of life of long-term care service users in Japan: a cross-sectional questionnaire study.

BACKGROUND: In Japan's super-aging society, the number of long-term care service providers is increasing, and the quality of care is a matter of concern. One aspect of the quality of care is the user's quality of life. The questionnaires EQ-5D and WHO-5 are representative indicators of quality of life. Herein, we aimed to measure the quality of life in long-term care service users in Japan and to clarify the relationship between quality of life and the level of care required. METHODS: A questionnaire study was conducted in 106 facilities of 22 corporations. In addition to the EQ-5D and WHO-5, sex, age, and the level of care required were assessed by descriptive statistics. Bonferroni's multiple comparison test was used to analyze each quality of life score, and the differences by sex and age were analyzed multiple regression analyses, with each quality of life score as the objective variable. RESULTS: Of 4647 cases collected, 2830 were analyzed, with no missing data. Both indicators tended to be lower than the general older population. Those scores tended to be higher in females than males (EQ-5D: males, 0.58 ± 0.26; females, 0.60 ± 0.24; P = 0.06 and WHO-5: males, 13.8 ± 5.92; females 14.9 ± 5.70; P < 0.001). In terms of age, those under 65 years old with specific diseases had lower EQ-5D scores than those in other age groups (P < 0.001); however, WHO-5 scores did not differ by age. Multiple regression analysis showed a significant association between the EQ-5D score and level of care required, except for support-required level 1, which tended to worsen as the level of care required increased. Conversely, the WHO-5 score was significantly lower for care need levels 2, 4, and 5. CONCLUSIONS: The quality of life of long-term care service users was worse than that of the general older population, it tended to be low among males and those under 65 years old with specific diseases. Furthermore, it gradually decreased as the level of care required increased. It is important to monitor users' quality of life as a quality indicator of care, to improve and manage it.

Balance dysfunction the most significant cause of in-hospital falls in patients taking hypnotic drugs: A retrospective study.

PURPOSE: Preventing falls in patients is one of the most important concerns in acute hospitals. Balance disorder and hypnotic drugs lead to falls. The Standing Test for Imbalance and Disequilibrium (SIDE) is developed for the evaluation of static standing balance ability. There have been no reports of a comprehensive assessment of falls risk including hypnotic drugs and SIDE. The purpose of this study was to investigate the fall rate of each patient who took the hypnotic drug and the factor associated with falls. METHODS: Fall rates for each hypnotic drug were calculated as follows (number of patients who fell/number of patients prescribed hypnotic drug x 100). We investigated the hypnotic drugs as follows; benzodiazepine drugs, Z-drugs, melatonin receptor agonists, and orexin receptor antagonists. Hypnotic drug fall rate was analyzed using Pearson's chi-square test. Decision tree analysis is the method we used to discover the most influential factors associated with falls. RESULTS: This study included 2840 patients taking hypnotic drugs. Accidents involving falls were reported for 211 of inpatients taking hypnotic drugs. Z-drug recipients had the lowest fall rate among the hypnotic drugs. We analyzed to identify independent factors for falls, a decision tree algorithm was created using two divergence variables. The SIDE levels indicating balance disorder were the initial divergence variable. The rate of falls in patients at SIDE level ≦ 2a was 14.7%. On the other hand, the rate of falls in patients at SIDE level ≧ 2b was 2.9%. Gender was the variable for the second classification. In this analysis, drugs weren't identified as divergence variables for falls. CONCLUSION: The SIDE balance assessment was the initial divergence variable by decision tree analysis. In order to prevent falls, it seems important not only to select appropriate hypnotic drugs but also to assess patients for balance and implement preventive measures.

Bio-signal Feature Analysis to Detect Aspiration Caused by Dysphagia.

Dysphagia causes aspiration symptoms and can trigger aspiration pneumonia, poor nutritional status, etc. To address these risks, it is important to properly evaluate dysphagia and link it with treatment and training. However, current dysphagia evaluation methods cannot assess a swallowing function equivalent to that in daily life, owing to the examination method and environment. In this study, we analyzed bio-signal features to realize a system that can detect aspiration symptoms in daily life. Focusing on the neck electrical impedance, swallowing sounds, and a surface electromyogram of the suprahyoid muscles, we created a swallowing-measurement device and analyzed the bio-signals of the throat movement during swallowing. By measuring the swallowing of dysphagic patients, we investigated the characteristic differences, depending on the presence or absence of aspiration symptoms. The analysis results suggest that there were differences in each bio-signal depending on the presence or absence of aspiration symptoms, and these bio-signals could detect aspiration symptoms. This method can detect aspiration symptoms in daily life and evaluate dysphagia more appropriately and simply than current evaluation methods.

Strength and morphology of a suprahyoid muscle and their relationship to forward head posture in healthy older adults.

AIM: Forward head posture, an abnormality in head and trunk positioning, adversely affects suprahyoid muscle activity. Jaw-opening force, which reflects suprahyoid muscle strength, is a useful index of dysphagia. However, the relationship between forward head posture and strength and morphology of suprahyoid muscles remains unclear. This study aims to clarify the relationship between forward head posture, jaw-opening force and morphology of suprahyoid muscles. METHODS: During October 2018, we enrolled older adults aged ≥65 years. The craniovertebral angle was measured, and an angle <49° was defined as forward head posture. Jaw-opening force was also measured. The geniohyoid muscle (GHM) was selected to represent the suprahyoid muscles, and its cross-sectional area and length were measured using ultrasonography. Sarcopenia was also determined based on the criteria of the 2019 Asian Working Group for Sarcopenia. Multiple regression analyses were conducted to determine the association between morphological characteristics of the suprahyoid muscle and jaw-opening force as well as the association between the former and forward head posture. RESULTS: Data of 87 participants were analyzed. Sex, cross-sectional area and length of the GHM, and sarcopenia were significantly associated with jaw-opening force. In addition, sex and forward head posture were significantly associated with the length of the GHM. CONCLUSIONS: Our study demonstrated that an overextended length of suprahyoid muscles mediates the relationship between forward head posture and jaw-opening force. Forward head posture is easily visualized and can be a useful indicator of decline in suprahyoid muscle strength. Geriatr Gerontol Int 2022; 22: 779-784.

Current Issues in Social Medicine and Public Health from the Viewpoint of Early-career Researchers: Summary of Opinions at the Social Medicine Young Retreat.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of research, practice, social contribution, and education in social medicine and public health, which relate to the core mission of universities. Early-career researchers and professionals play an important role in these domains, but little is known about the challenges and issues they encountered or recognized during this pandemic. Therefore, we summarized the opinions of 37 participants (30 early-career researchers and seven senior researchers) on this issue from discussions at the Social Medicine Young Retreat, 2019, of the Japanese Medical Science Federation. The retreat was initially planned to be held during March 5-6, 2020 in Yamanashi but was changed to be held virtually on March 5, 2021. Early-career researchers participated in group discussions on how social medicine should transform itself to serve the public during the COVID-19 pandemic. Afterward, each group provided opinions on challenges and issues in social medicine. For example, participants perceived difficulties in implementing research in a timely way and the lack of multidisciplinary collaboration. They recognized challenges in continuing practice because of the limited evidence on COVID-19. On social contribution, they described difficulties in communicating risk as professionals. They also noted issues arising from online teaching and learning. One group suggested that the essence of social medicine did not need to be changed, but methodologies should be updated to tackle multiple existing challenges. These opinions may not cover all issues but could help establish a better relationship between medicine and society in a bottom-up manner. The continuous promotion of interdisciplinary collaboration in social medicine (and basic and clinical medicine) would provide ideas to solve these issues at scale. Organizational support is warranted to ensure sustainability and scalability of these actions.

Association between Tongue Pressure and Jaw-Opening Force in Older Adults.

Tongue pressure (TP) is used to assess tongue muscle strength and is related to function and frailty. While performing TP, it is necessary to elevate the tongue and oral floor by contracting the suprahyoid muscles. However, the association between TP and suprahyoid muscle strength remains unclear. Accordingly, this study investigated the relationship between TP and jaw-opening force (JOF), an indicator of suprahyoid muscle strength. This cross-sectional study included 88 independent community-dwelling participants aged ≥65 years. Age, sex, and the number of remaining teeth were recorded. Ultrasonography was used to evaluate the cross-sectional area of the tongue and geniohyoid muscle, as representatives of the suprahyoid muscles. Sarcopenia was diagnosed based on appendicular skeletal muscle mass index, handgrip strength, and gait speed. Multiple regression analysis was performed with TP as the dependent variable. TP was significantly associated with JOF (ß = 0.371, p = 0.003). This study revealed that decreased TP was associated with a decline in JOF and suprahyoid muscle mass in older adults. Thus, low TP may be associated with decreased JOF. Prevention of the weakness of the suprahyoid muscles and maintaining TP may also contribute to the prevention of frailty associated with TP.

Verbascoside administered intrathecally attenuates hyperalgesia via activating mu-opioid receptors in a rat chronic constriction injury model.

BACKGROUND: Verbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health. Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved. METHODS: Chronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold-plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination. RESULTS: Verbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose-dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ-opioid receptor antagonist. CONCLUSIONS: These findings imply that verbascoside exerts an antihyperalgesic effect by activating µ-opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain. SIGNIFICANCE: Currently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long-term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first-line remedy for neuropathic pain. Natural products may be promising candidates for novel treatments of neuropathic pain.

The impact of sarcopenia on low back pain and quality of life in patients with osteoporosis.

PURPOSE: Osteoporosis combined with sarcopenia contributes to a high risk of falling, fracture, and even mortality. However, sarcopenia's impact on low back pain and quality of life (QOL) in patients with osteoporosis is still unknown. The purpose of this study is to investigate low back pain and QOL in osteoporosis patients with sarcopenia. METHODS: We assessed 100 ambulatory patients who came to our hospital for osteoporosis treatment. Low back pain was evaluated using the Visual Analogue Scale (VAS) with 100 being an extreme amount of pain and 0 no pain. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score was used to assess QOL after adjustment for age, history of vertebral fracture, and adult spinal deformity. Differences in low back pain intensity assessed by VAS between groups were evaluated by the Willcoxon rank-sum test. Covariance analysis was used to assess QOL. All data are expressed as either median, interquartile range, or average, standard error. RESULTS: Patients were classified into the sarcopenia group (n = 32) and the non-sarcopenia group (n = 68). Low back pain intensity assessed by VAS was significantly higher in the sarcopenia group than in the non-sarcopenia group (33.0 [0-46.6] vs. 8.5 [0-40.0]; p < 0.05). The subscales of the JOABPEQ for low back pain were significantly lower in the sarcopenia group than in the non-sarcopenia group (65.0 ± 4.63 vs. 84.0 ± 3.1; p < 0.05). CONCLUSION: In this cross-sectional study, sarcopenia affected low back pain and QOL in ambulatory patients with osteoporosis. Sarcopenia may exacerbate low back pain and QOL.

Jaw-Opening Force as a Useful Index for Dysphagia: A Cross-Sectional and Multi-Institutional Study.

INTRODUCTION: Jaw-opening force (JOF) can be a potential screening tool for dysphagia. However, confounding variables such as comorbidities or physical and oral functions that are associated with the physiology of swallowing have not previously been examined. Adjusting for these variables could reveal the relationship between JOF and dysphagia and indicate whether JOF is an independent factor associated with dysphagia. We therefore aimed to assess the efficacy of using JOF for dysphagia screening in this multi-institutional study. METHODS: Community-dwelling older adults over the age of 65 years (N = 403) who visited the university dental hospitals and participated in health surveys (mean age ± standard deviation, 77.1 ± 7.0 years; range, 65-96 years) between November 2018 and January 2020 were included in this study. The JOFs of all participants were measured. The measured JOF was compared with the presence of dysphagia, which was defined using the Functional Oral Intake Scale and the Eating Assessment Tool-10. RESULTS: Multiple logistic regression analysis revealed that the presence of dysphagia was independently associated with JOF, calf circumference, and dependence after adjusting for age and sex. DISCUSSION/CONCLUSION: Decreased JOF can be a risk factor for dysphagia in older adults.

Jaw-retraction exercise increases anterior hyoid excursion during swallowing in older adults with mild dysphagia.

OBJECTIVES: The present study aimed to evaluate the effectiveness of a newly designed jaw-retraction exercise for strengthening the geniohyoid muscle and thus improving the anterior movement of the hyoid bone during swallowing. BACKGROUND: Although previous studies suggest a relationship between anterior hyoid excursion and upper esophageal sphincter (UES) opening, there are currently no reports of physical exercises without the use of special equipment that can effectively improve this movement of the hyoid bone during swallowing. MATERIALS AND METHODS: This before-after study included patients presenting to the authors' hospital with mild dysphagia (Level 5 on the Dysphagia Outcome and Severity Scale). The participants were instructed to perform a jaw-retraction exercise designed to strengthen the geniohyoid muscle. Each participant was instructed to perform two sets of the exercise daily for four weeks, with each set consisting of five repetitions. Before and after the four-week training period, videofluoroscopic swallowing studies were performed and later analysed. RESULTS: Twenty-five patients with a median age of 77 were included. The median peak anterior hyoid position before and after exercise were 129.82 and 132.74 (%C2-C4 length), respectively, and this increase was found to be significant (P = .007). The median extent of UES opening before and after exercise were 8.6 and 9.3 (mm), respectively, and this increase was also found to be significant (P = .040). CONCLUSION: Our findings demonstrate that the jaw-retraction exercise can effectively improve the anterior movement of the hyoid bone. This exercise may be effective in individuals with oral frailty when signs of swallowing disorders are observed.

The effect of rotator cuff physical exercise combined with electrically stimulated antagonist on shoulder rotator cuff strength.

BACKGROUND: An elastic band (EB) is generally used with a low load for rotator cuff physical exercise, but the resulting increase in muscle strength is insufficient. We assessed the efficacy on external rotator muscle strength of the shoulder joint; of a hybrid training system (HTS) that resists the motion of a volitionally contracting agonist muscle using the force generated by its electrically stimulated antagonist vs. general rotator cuff exercise with EB. METHODS: Twenty healthy men with no shoulder joint disorders were randomized to 6 weeks of triweekly 10-min rotator cuff exercise with HTS or EB in a clinical research laboratory. Isokinetic concentric external rotator muscle strength at angular velocities of 60°/s and 180°/s (CON60, CON180, respectively) and isokinetic eccentric external rotator muscle strength at an angular velocity of 60°/s (ECC60) were measured as rotator cuff function before and after 6 weeks of intervention. RESULTS: There were no significant intergroup differences in baseline characteristics. There were statistically significant differences (p = 0.0358, p = 0.0213, respectively) in the increase in CON180 (mean ± SD) and ECC60 between the HTS group (Δ6.0 ± 6.0Nm, p = 0.015; Δ7.5 ± 4.7Nm p = 0.0007, respectively) and the EB group (Δ0.3 ± 5.2Nm, p = 0.8589; Δ1.8 ± 5.3 Nm p = 0.3133, respectively). There was a trend toward CON60 increasing in the HTS group (Δ4.7 ± 6.5Nm, p = 0.0494) which was greater than in the control group (Δ-0.9 ± 6.3Nm, p = 0.6637) (inter-group, p = 0.0677). CONCLUSIONS: The results of this study support the conclusion that HTS is more effective for increasing external rotator muscle strength more effectively than EB. HTS would be useful for rotator cuff physical exercise.

Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models.

Punicalagin, a natural polyphenolic compound classified as an ellagitannin, is a major ingredient of pomegranate (Punica granatum L.). Punicalagin has potent antioxidant and anti-inflammatory effects. Although the antinociceptive effects of orally administered pomegranate extracts have been reported, little is known about the effect of punicalagin on nociceptive transmission in the central nervous system. We examined whether punicalagin ameliorates neuropathic pain and inflammatory pain in the spinal cord. Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve, and an intrathecal catheter was implanted for drug administration. The electronic von Frey test and cold-plate test were performed in CCI rats to evaluate mechanical and cold hyperalgesia in neuropathic pain, and the formalin test was performed in normal rats to evaluate acute and persistent inflammatory pain. An open-field test was conducted to explore whether punicalagin affects locomotor activity in CCI rats. Punicalagin administered intrathecally attenuated mechanical and cold hyperalgesia to the same degree as gabapentin in CCI rats and reduced pain-related behaviors in both the early and late phases in formalin-injected rats. Punicalagin did not affect motor function. These results suggest that punicalagin exerts an antinociceptive effect in the spinal cord without motor deficit, thus showing therapeutic potential for neuropathic pain and inflammatory pain.

Can Videofluoroscopic Swallowing Kinematic Analysis Predict Recovery of Oral Intake in Postoperative Oral Cancer Patients Requiring Nasogastric Tube Feeding?

This retrospective study determined the significant predictive factors for the number of days required to remove nasogastric tubes (NGTs) after surgery in patients with oral cancer (OC). In this study, patients underwent a videofluoroscopic swallowing study (VFSS) approximately 2 weeks after surgery. Videofluoroscopic images were analyzed, and variables such as swallowing and swallowing kinematics were measured. Patient characteristics, swallowing kinematics, and swallowing results were assessed using a Cox proportional hazards model. This study assessed 129 participants (66 men, 63 women, mean age: 69.0 ± 14.1 years) with nine types of cancer. The Cox proportional hazard ratio revealed that sex, body mass index before surgery, radiotherapy and/or chemotherapy, dysphagia before surgery, normalized pharyngeal constriction ratio, upper esophageal sphincter (UES) opening, and laryngeal vestibule disclosure (LVC) disorder were predictive factors for the removal of NGTs when adjusted for age. The study identified several predictive factors for the removal of NGTs and oral intake recovery in patients with OC. Regarding swallowing kinematics, UES opening is the most significant predictive factor. After surgery for OC, VFSS should be performed to assess safe eating methods and predict the recovery of oral intake and removal of the NGT.

Optimal application of stereotactic body radiotherapy and radiofrequency ablation treatment for different multifocal hepatocellular carcinoma lesions in patients with Barcelona Clinic Liver Cancer stage A4-B1: a pilot study.

BACKGROUND: In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4-B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4-B1 patients. METHODS: From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). RESULTS: The median follow-up duration was 31.3 months (range: 15.1-71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8-45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months' observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin-bilirubin grade, respectively. CONCLUSIONS: For patients with BCLC stage A4-B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

Effects of a low-intensity resistance exercise program on serum miR-630, miR-5703, and Fractalkine/CX3CL1 expressions in subjects with No exercise habits: A preliminary study.

AIMS: Exercise is effective for the prevention of liver cancer. Exercise exerts biological effects through the regulation of microRNAs (miRNAs) and cytokines/myokines. We aimed to investigate the effects of low-intensity resistance exercise on serum miRNA and cytokine/myokine expressions in subjects with no exercise habits. METHODS: We enrolled seven male subjects with no exercise habits in this prospective before-after study. All subjects performed a low-intensity resistance exercise program (three metabolic equivalents, approximately 20 min/session). Serum miRNA expressions were evaluated using microarrays. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed miRNAs before and after exercise. Serum cytokine/myokine expressions were evaluated using a multiplex panel. RESULTS: All subjects completed the exercise program with no adverse events. In the microarray analysis, seven miRNAs showed a significant change between before and after exercise. Of these, microRNA (miR)-630 and miR-5703 showed a >1.5-fold increase (miR-630: 40.7 vs. 69.3 signal intensity, p = 0.0133; miR-5703: 30.7 vs. 55.9 signal intensity, p = 0.0051). KEGG pathway enrichment analysis showed that miR-630- and miR-5703-related genes were enriched in 37 and 5 pathways, including transforming growth factor-beta and Wnt signaling pathways, respectively. In the multiplex analysis, 12 cytokines/myokines showed significant alteration after exercise compared to before exercise. Of these, fractalkine/CX3CL1 showed the most significant up-regulation by exercise (94.5 vs. 109.1 pg/ml, p = 0.0017). CONCLUSIONS: A low-intensity resistance exercise program was associated with upregulation of serum miR-630, miR-5703, and fractalkine/CX3CL1 expressions in subjects with no exercise habits. Thus, even low-intensity exercise may alter miRNA and cytokine/myokine expressions in humans.

Sofosbuvir-based therapies associated with regression of liver fibrosis in patients with hepatitis C virus infection: A prospective observational study.

ABSTRACT: Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2  cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.

Inhibitory effect of intrathecally administered AM404, an endocannabinoid reuptake inhibitor, on neuropathic pain in a rat chronic constriction injury model.

BACKGROUND: The endocannabinoid system modulates a wide variety of pain conditions. Systemically administered AM404, an endocannabinoid reuptake inhibitor, exerts antinociceptive effects via activation of the endocannabinoid system. However, the mechanism and site of AM404 action are not fully understood. Here, we explored the effect of AM404 on neuropathic pain at the site of the spinal cord. METHODS: Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effects of intrathecal administration of AM404 on mechanical and cold hyperalgesia were examined using the electronic von Frey test and cold plate test, respectively. Motor coordination was assessed using the rotarod test. To understand the mechanisms underlying the action of AM404, we tested the effects of pretreatment with the cannabinoid type 1 (CB1) receptor antagonist AM251, CB2 receptor antagonist AM630, and transient receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine. RESULTS: AM404 attenuated mechanical and cold hyperalgesia with minimal effects on motor coordination. AM251 significantly inhibited the antihyperalgesic action of AM404, whereas capsazepine showed a potentiating effect. CONCLUSIONS: These results indicate that AM404 exerts antihyperalgesic effects primarily via CB1, but not CB2, receptor activation at the site of the spinal cord. TRPV1 receptors appear to play a pronociceptive role in CCI rats. The endocannabinoid reuptake inhibitor may be a promising candidate treatment for neuropathic pain.