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Purpose: This study evaluated the efficacy and safety of transvaginal approach combined intracavitary and interstitial brachytherapy (IC/IS BT) assisted by transrectal ultrasound (TRUS) for treatment of locally advanced cervical cancer (LACC). Materials and Methods: A total of 30 patients of LACC treated with external beam radiotherapy and IC/IS BT via transvaginal approach assisted by transrectal ultrasound were observed retrospectively. The 2-year local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan–Meier method. Late adverse events were also evaluated to assess the safety of IC/IS BT. Results: The median follow-up period was 22 months. The 2-year LC, PFS, and OS were 90%, 61%, and 82%, respectively. We observed no critical complications related to the IC/IS BT technique. Late adverse events of grade 3 or more included one case of grade 4 colon perforation. Conclusion: Our patient series demonstrated that radiotherapy combined with transvaginal approach, TRUS-assisted IC/IS BT achieves favorable local control and safety for LACC. [ABSTRACT FROM AUTHOR]

Background: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste. Methods: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance – time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes. Results: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min). Conclusions: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing. [ABSTRACT FROM AUTHOR]

Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research. [ABSTRACT FROM AUTHOR]

Purpose: This study compared concentric–eccentric coupled (CON-ECC), concentric-only (CON), and eccentric-only (ECC) resistance training of the elbow flexors for their effects on muscle strength and hypertrophy. Methods: Non-resistance-trained young adults were assigned to one of the four groups: CON-ECC (n = 14), CON (n = 14) and ECC (n = 14) training groups, and a control group (n = 11) that had measurements only. The training group participants performed dominant arm elbow flexor resistance training in extended elbow joint angles (0°–50°) twice a week for 5 weeks. The total training volume (dumbbell weight × number of contractions) in CON-ECC (5745 ± 1020 kg) was double of that in CON (2930 ± 859 kg) and ECC (3035 ± 844 kg), because 3 sets of 10 contractions were performed for both directions in CON-ECC. Maximum voluntary isometric (MVC-ISO), concentric (MVC-CON), and eccentric contraction (MVC-ECC) torque of the elbow flexors and biceps brachii and brachialis muscle thickness (MT) were measured at baseline, and 3–9 days post-last training session. Results: No significant changes in any measures were evident for the control group. The CON-ECC and ECC groups showed increases (P < 0.05) in MVC-ISO (12.0 ± 15.7% and 11.3 ± 10.8%, respectively) and MVC-ECC torque (12.5 ± 18.3%, 16.2 ± 11.0%) similarly. Increases in MVC-CON torque (P < 0.05) were evident for the CON-ECC (17.5 ± 13.5%), CON (10.5 ± 12.8%), and ECC (14.2 ± 10.4%) groups without a significant difference among groups. MT increased (P < 0.01) after CON-ECC (10.6 ± 5.4%) and ECC (9.7 ± 7.2%) similarly, but not significantly after CON (2.5 ± 4.8%). Conclusions: ECC training increased muscle strength and thickness similarly to CON-ECC training, despite the half training volume, suggesting that concentric contractions contributed little to the training effects. [ABSTRACT FROM AUTHOR]

Background: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Methods: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Results: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Conclusion: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant. [ABSTRACT FROM AUTHOR]

We investigated the biofilm removal effects of laser activated irrigation (LAI) using a pig model, focusing on the impact of the fiber tip position, and used a high-speed camera to observe the occurrence and positioning of the cavitation associated with laser irradiation. A total of 16 roots of deciduous mandibular second premolars from 4 pigs were used. After a pulpectomy, the canals were left open for 2 weeks and sealed for 4 weeks to induce intraradicular biofilm. Root canal irrigation was then performed with Er:YAG laser activation. The fiber tip was inserted at two different positions, i.e., into the root canal in the intracanal LAI group and into the pulp chamber in the coronal LAI group. Intracanal needle irrigation with saline or 5% NaOCl was utilized in the positive control and conventional needle irrigation (CNI) groups. SEM and qPCR were carried out to evaluate treatment efficacy. Statistical analysis was performed using ANOVA and a Tukey–Kramer post-hoc test for qPCR and with a Steel–Dwass test to compare the SEM scores, with α = 0.05. A high-speed camera was used to observe the generation of cavitation bubbles and the movement of the induced bubbles after laser irradiation. The intracanal and coronal LAI groups showed significantly lower amounts of bacteria than either the positive control or CNI groups. There was no significant difference found between the intracanal and coronal LAI groups. SEM images revealed opened dentinal tubules with the destruction of biofilm in both LAI groups. High-speed camera images demonstrated cavitation bubble production inside the root canal after a single pulse irradiation pulse. The generated bubbles moved throughout the entire internal multi-rooted tooth space. Coronal LAI can generate cavitation in the root canal with a simply placed fiber inside the pulp chamber, leading to effective biofilm removal. This method could thus contribute to the future development of endodontic treatments for refractory apical periodontitis caused by intraradicular biofilm. [ABSTRACT FROM AUTHOR]

Both quality and quantity of skeletal muscle are considered important for prognostic factors and clinical outcomes in solid cancers. However, few studies have examined both quality and quantity of skeletal muscle in patients with hematological malignancies. The aim of the present study was to clarify the prevalence of low skeletal muscle quantity and quality and their associated factors in patients before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Pretransplant plain CT imaging at the third lumber vertebra level was used to measure the psoas muscle mass index (PMI) and the intramuscular adipose tissue content (IMAC) in 113 adult patients (age 47.1 ± 14.6 years) before HSCT. We analyzed the factors associated with PMI and IMAC, respectively. Although 62.8% of all patients had low skeletal muscle mass, only 8% had poor skeletal muscle quality. Multivariable logistic analysis showed that older age [odds ratio (OR) = 2.45, confidence interval (CI) = 1.04–5.76, P = 0.04], male (OR = 4.35, CI = 0.05–0.97, P = 0.04), and low BMI (OR = 0.83, CI = 0.71–0.97, P = 0.02) were independent risk factors for low PMI before HSCT. Only age (≤ 50 years) was significantly associated with muscle quality (modified OR = 0.07, CI = 0.00–0.43, P < 0.01) in univariate analysis. Most patients already showed low skeletal muscle mass before allo-HSCT although skeletal muscle quality was relatively preserved. These results may be indicative of pre-cachexia and may be useful for its long-term management in allo-HSCT patients. [ABSTRACT FROM AUTHOR]

Introduction: Anterior cruciate ligament (ACL) reconstruction using hamstring tendons may involve harvesting of the gracilis tendon in addition to the semitendinosus tendon (ST) depending on the size of the ST graft. However, the effect of gracilis harvesting in addition to ST harvesting on muscle strength, such as the hamstring-to-quadriceps (HQ) ratio, remains unclear. Hence, this study aimed to investigate the effect of gracilis harvesting on subsequent knee muscle strength. Materials and methods: Eighty-two patients who underwent ACL reconstruction were included in this retrospective study. They were divided into the following two groups depending on the tendon graft used for ACL reconstruction: the ST group (41 patients) and the semitendinosus tendon/gracilis tendon (STG) group (41 patients). The isokinetic peak torque of the knee extensor and flexor was measured using a BIODEX dynamometer at a velocity of 60°/s and 180°/s, respectively, 3 and 6 months after ACL reconstruction. The groups were compared in terms of the limb symmetry index (LSI) and HQ ratio. Results: The significant difference in the knee flexor of the LSI at 6 months after ACL reconstruction was as follows: ST group, 120.3 ± 28.3 vs STG group, 105.6 ± 19.0 (p < 0.01) at 60°/s and ST group, 122.9 ± 35.2 vs STG group, 106.2 ± 24.6 (p = 0.02) at 180°/s. There were significant differences in the HQ ratio at 180°/s as follows: ST group, 0.67 ± 0.15 vs STG group, 0.60 ± 0.13 (p < 0.01) at 3 months and ST group, 0.67 ± 0.13 vs STG group, and 0.59 ± 0.12 (p < 0.01) at 6 months after ACL reconstruction. Conclusions: Gracilis tendon harvesting may contribute to a decrease in knee flexor strength and HQ ratio with fast contraction. Thus, the need for gracilis tendon harvesting in ACL reconstruction should be carefully considered. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a one-dimensional (1-D) model for predicting the amount of unburned hydrocarbons (UHC) due to flame extinction by quenching close to the combustion chamber wall in a gasoline engine. The local Reynolds number was used to predict the thickness of the thermal boundary layer developed by in-cylinder flow caused by high speed charge passing through the intake valves. The effect of different intake port geometries, including moderate- and high-tumble types, on the thickness of the thermal boundary layer was examined. The flame extinction model was integrated into a 1-D gasoline engine model. The amount of UHC predicted by the model was compared with experimental results by using a single-cylinder gasoline engine under various engine operating conditions. The numerical values were found to be in reasonable agreement with the measured data. A methodology for controlling UHC was also proposed in the final section. [ABSTRACT FROM AUTHOR]

In this study, we examined the antileukemic effects of pterostilbene, a natural methylated polyphenol analog of resveratrol that is predominantly found in berries and nuts, using various human and murine leukemic cells, as well as bone marrow samples obtained from patients with leukemia. Pterostilbene administration significantly induced apoptosis of leukemic cells, but not of non-malignant hematopoietic stem/progenitor cells. Interestingly, pterostilbene was highly effective in inducing apoptosis of leukemic cells harboring the BCR/ABL fusion gene, including ABL tyrosine kinase inhibitor (TKI)-resistant cells with the T315I mutation. In BCR/ABL+ leukemic cells, pterostilbene decreased the BCR/ABL fusion protein levels and suppressed AKT and NF-κB activation. We further demonstrated that pterostilbene along with U0126, an inhibitor of the MEK/ERK signaling pathway, synergistically induced apoptosis of BCR/ABL+ cells. Our results further suggest that pterostilbene-promoted downregulation of BCR/ABL involves caspase activation triggered by proteasome inhibition-induced endoplasmic reticulum stress. Moreover, oral administration of pterostilbene significantly suppressed tumor growth in mice transplanted with BCR/ABL+ leukemic cells. Taken together, these results suggest that pterostilbene may hold potential for the treatment of BCR/ABL+ leukemia, in particular for those showing ABL-dependent TKI resistance. [ABSTRACT FROM AUTHOR]

Purpose: Passive torque during static stretching was decreased. This phenomenon occurs due to stress relaxation. However, no studies have investigated the relationship stress relaxation and changes in range of motion (ROM) or muscle–tendon unit stiffness. Moreover, no study calculated the total volume during static stretching as total work and investigated the relationship between total work and ROM changes or muscle–tendon stiffness. This study aimed to investigate the relationship between stress relaxation, total work from measuring passive torque normalized by muscle thickness and ROM, and muscle–tendon stiffness. Methods: A total of 63 healthy students voluntarily participated in this study. Static stretching was performed for the plantar flexor muscles at 120 s. Outcomes were assessed on ROM, passive torque at dorsiflexion ROM, and muscle–tendon stiffness. Stress relaxation was defined as the change of torque from the start to end of static stretching. Total work was defined as the sum of the torque from the start to end of static stretching. Results: Stress relaxation was found to be significantly correlated with muscle–tendon stiffness whether normalized by muscle thickness or not (r = 0.603, r = 0.599). Furthermore, total work was significantly correlated with muscle–tendon stiffness, regardless of normalization (r = − 0.276, r = − 0.327). However, the relationship among stress relaxation, total work and ROM, and passive torque at dorsiflexion ROM was not significant. Conclusion: Stress relaxation and total work are associated with muscle–tendon stiffness changes after stretching, but not associated with ROM changes. [ABSTRACT FROM AUTHOR]

Birth order is a crucial environmental factor for child development. For example, later-born children are relatively unlikely to feel secure due to sibling competition or diluted parental resources. The positive effect of being earlier-born on cognitive intelligence is well-established. However, whether birth order is linked to social behavior remains controversial, and the neural correlates of birth order effects in adolescence when social cognition develops remain unknown. Here, we explored the birth order effect on prosociality using a large-scale population-based adolescent cohort. Next, since the amygdala is a key region for sociality and environmental stress, we examined amygdala substrates of the association between birth order and prosociality using a subset neuroimaging cohort. We found enhanced prosociality in later-born adolescents (N = 3160), and observed the mediating role of larger amygdala volume (N = 208) and amygdala-prefrontal functional connectivity with sex-selective effects (N = 183). We found that birth order, a non-genetic environmental factor, affects adolescent social development via different neural substrates. Our findings may indicate the later-born people's adaptive survival strategy in stressful environments. [ABSTRACT FROM AUTHOR]

Machine learning classifiers for psychiatric disorders using resting-state functional magnetic resonance imaging (rs-fMRI) have recently attracted attention as a method for directly examining relationships between neural circuits and psychiatric disorders. To develop accurate and generalizable classifiers, we compiled a large-scale, multi-site, multi-disorder neuroimaging database. The database comprises resting-state fMRI and structural images of the brain from 993 patients and 1,421 healthy individuals, as well as demographic information such as age, sex, and clinical rating scales. To harmonize the multi-site data, nine healthy participants ("traveling subjects") visited the sites from which the above datasets were obtained and underwent neuroimaging with 12 scanners. All participants consented to having their data shared and analyzed at multiple medical and research institutions participating in the project, and 706 patients and 1,122 healthy individuals consented to having their data disclosed. Finally, we have published four datasets: 1) the SRPBS Multi-disorder Connectivity Dataset 2), the SRPBS Multi-disorder MRI Dataset (restricted), 3) the SRPBS Multi-disorder MRI Dataset (unrestricted), and 4) the SRPBS Traveling Subject MRI Dataset. Measurement(s) mental or behavioural disorder • brain measurement • Demographic Data Technology Type(s) functional magnetic resonance imaging • magnetic resonance imaging • Resting State Functional Connectivity Magnetic Resonance Imaging Factor Type(s) age • sex • site • disorder Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14716329 [ABSTRACT FROM AUTHOR]

Background: The International Federation of Gynecology and Obstetrics (FIGO) staging system for Müllerian cancer was changed in 2014. Our objective was to evaluate the prognostic impact of stage IV subclassification in this new staging system, especially focusing on extra-abdominal lymph node metastasis. Methods: Eighty-two patients with stage IV Müllerian cancer treated between 2005 and 2016 at our hospital were retrospectively analyzed. Data for the following clinicopathological variables were analyzed: (1) FIGO stage; (2) tumor stage; (3) lymph node status; (4) histologic type; (5) neoadjuvant chemotherapy; (6) optimal surgery; and (7) bevacizumab use. Survival analysis was performed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. Results: In accordance with the new classification, 28 and 54 patients were classified as FIGO IVA and IVB, respectively. In the Cox proportional hazards model, early-stage tumors (T1b–3b) and optimal surgery were statistically significant favorable prognostic factors. However, the new FIGO system did not discriminate prognostically between stage IVA and IVB. Median overall survival of stage IVB patients diagnosed with extra-abdominal lymph node metastasis only was better than that of stage IVA and stage IVB patients diagnosed with solid organ metastasis. Conclusions: In this analysis of the revised FIGO system of patients reclassified as FIGO stage IVA or IVB, no new prognostic information was obtained. There is a possibility that stage IVB patients diagnosed with extra-abdominal lymph node metastasis only can be classified as an earlier stage. Further modification of the FIGO staging system may be needed to improve the prediction of patient prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The application of superficial icing has often been used in rehabilitation and sport settings. Some previous studies have shown that superficial icing or cooling increased range of motion and muscle stiffness. Considering that previous studies have investigated the effects of superficial icing only after 20 or 30 min, the superficial icing duration needed to increase range of motion has remained unclear. Moreover, another study showed that superficial icing increased spinal excitability, which could consequently increase muscle stiffness, although no study has investigated the relationship between change in muscle stiffness and change in spinal excitability after superficial cooling. The aims of this study was to determine the time required to increase range of motion by investigating changes over time during superficial icing and elucidate the mechanism whereby superficial cooling increased muscle stiffness by investigating the changes in muscle temperature and spinal cord excitability. Methods: A total of 19 healthy volunteers participated in 2 experiments, the first of which sought to determine time-course changes in medial gastrocnemius muscle stiffness, dorsiflexion range of motion, passive torque at dorsiflexion range of motion during superficial icing and the second of which sought to investigate the time-course changes in spinal cord excitability in the dominant leg. Results and conclusion: Our results showed that more than 5 min of superficial icing is required to increase range of motion, while the increase in muscle stiffness could be attributed to the decrease in muscle temperature and not change in spinal excitability. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan. Methods: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities' experience with clinical research on SN biopsy. Results: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%). Conclusion: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan. [ABSTRACT FROM AUTHOR]

Purpose: Static stretching (SS) is performed in various settings, but there is no consensus about the effects of SS programmes on changes in muscle morphofunction. This study aimed to investigate the effects of a high-volume SS programme on muscle strength and architecture. Methods: Sixteen healthy young male adults participated, and the dominant leg was defined as the intervention side, with the non-dominant leg as the control side. Stretching exercises were performed two times per week (6 sets of 5 min, totally 30 min per session,) for 5-week using a stretching board under the supervision of the research team. Before and after SS intervention programme, plantar-flexor strength (maximum voluntary isometric contraction, MVC-ISO; maximum voluntary concentric contraction, MVC-CON) and architecture (muscle thickness, pennation angle, and fascicle length) were measured via dynamometer and ultrasound, respectively. Results: Following the SS-training programme, significant increases were observed for stretching side in MVIC-ISO at neutral ankle position (p = 0.02, d = 0.31, Δ = 6.4 ± 9.9%) and MVC-CON at 120°/s (p = 0.02, d = 0.30, Δ = 7.8 ± 9.1%), with no significant change on the control side. There was no significant change in any measure of muscle architecture for both intervention and control sides. Conclusion: Five-week high-volume SS induced positive changes on some measures of muscle strength but not hypertrophy of plantar-flexor muscles. Even with a volume much greater than already tested, the low strain offered by the SS per set seems be insufficient to induce architectural changes on skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years. Methods: Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes. Results: The mean patient age was 34 years (range 18–64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio [HR], 1.028; 95% CI 1.005–1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008–1.098; P = 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353–2.846; P = 0.0004). Conclusions: Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence. [ABSTRACT FROM AUTHOR]

The structural mechanisms of single-pass transmembrane enzymes remain elusive. Kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases. Here, we report the mammalian full-length structure of KMO in its membrane-embedded form, complexed with compound 3 (identified internally) and compound 4 (identified via DNA-encoded chemical library screening) at 3.0 Å resolution. Despite predictions suggesting that KMO has two transmembrane domains, we show that KMO is actually a single-pass transmembrane protein, with the other transmembrane domain lying laterally along the membrane, where it forms part of the ligand-binding pocket. Further exploration of compound 3 led to identification of the brain-penetrant compound, 5. We show that KMO is dimeric, and that mutations at the dimeric interface abolish its activity. These results will provide insight for the drug discovery of additional blood-brain-barrier molecules, and help illuminate the complex biology behind single-pass transmembrane enzymes. Mimasu et al. report a rat full-length structure of kynurenine 3-monooxygenase (KMO) in its membrane-embedded form, complexed with two inhibitors. They find that the dimeric interface of KMO is critical for its activity. This study provides insights into the drug development strategies that target KMO, an important regulator of tryptophan metabolism. [ABSTRACT FROM AUTHOR]

Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. Methods: Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. Results: Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12–146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. Conclusion: Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation. [ABSTRACT FROM AUTHOR]

Background: Metastatic tumors to the breast reportedly account for 0.5% to 2.0% of all malignant breast diseases. Such metastatic tumors must be differentiated from primary breast cancer. Additionally, few reports have described metastases of gynecological cancers to the breast. We herein report two cases of metastasis of pelvic high-grade serous adenocarcinoma to the breast. Case presentation: The first patient was a 57-year-old woman with a transverse colon obstruction. Colostomy was performed, but the cause of the obstruction was unknown. We found scattered white nodules disseminated throughout the abdominal cavity and intestinal surface. Follow-up contrast-enhanced computed tomography (CT) showed an enhanced nodule outside the right mammary gland. Core needle biopsy (CNB) of the right breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. We diagnosed the patient's condition as breast and lymph node metastasis of a high-grade serous carcinoma of the female genital tract. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. The second patient was a 71-year-old woman with a medical history of low anterior resection for rectal cancer at age 49, partial right thyroidectomy for follicular thyroid cancer at age 53, and left lower lung metastasis at age 57. Periodic follow-up CT showed peritoneal dissemination, cancerous peritonitis, and pericardial effusion, and the patient was considered to have a cancer of unknown primary origin. Contrast-enhanced CT showed an enhanced nodule in the left mammary gland with many enhanced nodules and peritoneal thickening in the abdominal cavity. CNB of the left breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. Conclusions: We experienced two rare cases of intramammary metastasis of high-grade serous carcinoma of female genital tract origin. CNB was useful for confirming the histological diagnosis of these cancers that had originated from other organs. A correct diagnosis of such breast tumors is important to ensure quick and appropriate treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. Methods: A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum β-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. Results: The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5–25.1) vs. 3.7 (0.0–7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. Conclusion: Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period. [ABSTRACT FROM AUTHOR]

Thermal and evolved gas analyses were carried out to assess the decomposition of an ionic liquid propellant consisting of ammonium dinitramide (ADN), methylammonium nitrate (MMAN) and urea, using thermogravimetry–differential scanning calorimetry–high-resolution time-of-flight mass spectrometry (TG–DSC–HRTOFMS). This technique simultaneously assesses the thermal and evolved gas behavior and is able to distinguish between products having similar mass-to-charge ratios, based on accurate mass determinations. ADN/MMAN and ADN/MMAN/urea mixtures were found to decompose to form NH3, H2O, HCN, CO, N2, CH2O, CH3NH2, HNCO, CO2, N2O and HNO3, and possible reaction schemes for the decomposition processes were developed. Interactions between ADN and MMAN appear to enhance the generation of N2, while the presence of urea reduces the net exothermic heat of reaction due to the endothermic pyrolysis reaction of urea to NH3 and HNCO, followed by the reaction HNCO + H2O → NH3 + CO2. [ABSTRACT FROM AUTHOR]

Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted. [ABSTRACT FROM AUTHOR]

Background: The baseline data obtained in the CKD-JAC demonstrated that insufficient treatment was being provided for renal anemia by institutions specializing in renal disease. The objective of this study was to investigate the status of treatment for renal anemia, including renal/cardiovascular outcomes and mortality, at regional medical facilities since the development of long-acting erythropoiesis-stimulating agents (LA-ESA). Methods: Non-dialysis outpatients with chronic kidney disease and renal anemia were eligible. Anemia was treated based on the clinical condition of each patient and targeted hemoglobin (Hb) levels. Results: A total of 283 patients from 21 institutions were enrolled and followed up for a maximum of 3 years. A doubling of the serum creatinine level was observed in 89 patients, and renal replacement therapy was initiated in 57 patients. Multivariate Cox regression analysis revealed that a lower mean Hb level (mHb) and receiving fewer frequency of ESA during the follow-up period were independent determinants of the composite renal outcome and overall mortality. During the follow-up period, the percentages of patients with mHb of 10–10.9 g/dL and ≥ 11 g/dL were increased. Similar trends were seen regardless of whether the patients were treated by nephrologists or non-nephrologists. The frequency of ESA treatment was increased among the patients treated by non-nephrologists; however, it was much lower than nephrologists. Conclusion: This study demonstrated that, in the era of LA-ESA treatment, higher Hb levels are associated with reduced composite renal outcomes at regional medical facilities. The importance of renal anemia management should be highlighted, even among non-nephrologists. [ABSTRACT FROM AUTHOR]

Purpose: Lately, awake surgery has been frequently adapted for glioblastoma (GBM). However, even with awake surgery, the expected long-term independence levels may not be achieved. We studied the characteristics of independence levels in GBM patients, and investigated the usefulness and parameter thresholds of awake surgery from the standpoint of functional outcomes. Methods: Totally, 60 GBM patients (awake group, n = 30; general anesthesia group, n = 30) who underwent tumor resection surgery were included. We collected preoperative and 1- and 3-month postoperative Karnofsky Performance Status (KPS) scores, and analyzed causes of low KPS scores from the aspect of function, brain region, and clinical factors. Then, we focused on the operative method, and investigated the usefulness of awake surgery. Finally, we explored the parameter standards of awake surgery in GBM considering independence levels. Results: Postoperative KPS were significantly lower than preoperative scores. Responsible lesions for low KPS scores were deep part of the left superior temporal gyrus and the right posterior temporal gyri that may be causes of aphasia and neuropsychological dysfunctions, respectively. Additionally, operative methods influenced on low independence level; long-term KPS scores in the awake group were significantly higher than those in the general anesthesia group, but they depended on age and preoperative KPS scores. Receiver operating characteristic curve analysis showed preoperative KPS = 90 and age = 62 years as the cutoff values for preservation of long-term KPS scores in awake group. Conclusion: Awake surgery for GBM is useful for preserving long-term independence levels, but outcomes differ depending on age and preoperative KPS scores. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy.Methods: A total of 139 patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group.Results: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group.Conclusions: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted. [ABSTRACT FROM AUTHOR]

Introduction: High-dose chemotherapy for remission induction can induce cardiac toxicity prior to hematopoietic stem cell transplantation (HSCT). However, the details of cardiac function in patients undergoing HSCT are unclear, particularly during exercise. The aim of present study was to evaluate cardiac output responses to exercise in patients after high-dose chemotherapy before HSCT compared with in age-matched healthy controls.Methods: Twenty-nine patients before HSCT (age 44.6 ± 15.2 years) and 13 controls (45.8 ± 16.0 years) performed the 6-min walk test (6MWT). Cardiac output (CO), stroke volume (SV), heart rate (HR), and cardiac index (CI) were continuously measured during the 6MWT using the noninvasive thoracic impedance method.Results: No significant difference was observed in the six-minute walk distance (6MD) between the two groups. SV, CO, and CI both at rest and the end of the 6MWT in the patients were significantly lower, compared with the controls, but there was no significant difference in HR. In all subjects, the 6MD was positively correlated with SV, CO, CI, and HR after the 6MWT.Conclusion: These findings suggest that cardiac output response to exercise indicates exercise intolerance, which may not be detected by 6MD in patients before HSCT. [ABSTRACT FROM AUTHOR]

In Japan, almost all patients with knee arthritis and WSD have shown the right knee in valgus and left knee in varus with 15 out of 17 patients with the WSD showing right knees having valgus deformity across five articles written in Japanese. Therefore, researchers have discussed the aetiology of the knee WSD and the reason why valgus deformity is usually observed in the right knee. Letter to the Editor concerning "Alterations of 3D acetabular and lower limb parameters in adolescent idiopathic scoliosis" by Karam M, et al. (Eur Spine J [2020]; 29(8):2010-2017): Does windswept deformity of the knee exist in 274 participants with adolescent idiopathic scoliosis?. [Extracted from the article]

Metal-based additive manufacturing, or three-dimensional (3D) printing, is a potentially disruptive technology across multiple industries, including the aerospace, biomedical and automotive industries. Building up metal components layer by layer increases design freedom and manufacturing flexibility, thereby enabling complex geometries, increased product customization and shorter time to market, while eliminating traditional economy-of-scale constraints. However, currently only a few alloys, the most relevant being AlSi10Mg, TiAl6V4, CoCr and Inconel 718, can be reliably printed; the vast majority of the more than 5,500 alloys in use today cannot be additively manufactured because the melting and solidification dynamics during the printing process lead to intolerable microstructures with large columnar grains and periodic cracks. Here we demonstrate that these issues can be resolved by introducing nanoparticles of nucleants that control solidification during additive manufacturing. We selected the nucleants on the basis of crystallographic information and assembled them onto 7075 and 6061 series aluminium alloy powders. After functionalization with the nucleants, we found that these high-strength aluminium alloys, which were previously incompatible with additive manufacturing, could be processed successfully using selective laser melting. Crack-free, equiaxed (that is, with grains roughly equal in length, width and height), fine-grained microstructures were achieved, resulting in material strengths comparable to that of wrought material. Our approach to metal-based additive manufacturing is applicable to a wide range of alloys and can be implemented using a range of additive machines. It thus provides a foundation for broad industrial applicability, including where electron-beam melting or directed-energy-deposition techniques are used instead of selective laser melting, and will enable additive manufacturing of other alloy systems, such as non-weldable nickel superalloys and intermetallics. Furthermore, this technology could be used in conventional processing such as in joining, casting and injection moulding, in which solidification cracking and hot tearing are also common issues. [ABSTRACT FROM AUTHOR]

Purpose: The diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) is able to diagnose DIC accurately and promptly. The aim of this retrospective study is to evaluate the degree of association between each parameter of JAAM DIC criteria and the diagnosis of trauma induced DIC (T-DIC) utilizing thromboelastometry (ROTEM). Methods: Trauma patients transported to our hospital with ROTEM performed in the emergency department between January 2013 and December 2015 were enrolled in this study. We evaluated (1) the characteristics of T-DIC, (2) the relationships between T-DIC and each parameter of the JAAM DIC criteria and (3) the diagnostic accuracies of each parameter for T-DIC by statistical measurement. Results: All 72 patients (21 T-DIC and 51 control) were included in primary analysis. T-DIC was significantly related to younger age, more severe trauma scores, more cases of massive transfusions, and remarkable coagulation abnormality detected by standard coagulation tests. In the cases of T-DIC, ROTEM showed longer clotting time, lower acceleration, lower clot firmness, and inhibited fibrinolysis in EXTEM/INTEM. Within the JAAM DIC score, PT-INR ≥1.2 was the most accurate factor for T-DIC diagnosis; sensitivity 60.0%, specificity 100.0%, and accuracy 88.7%. PT-INR ≥1.2 was statistically correlated with the JAAM DIC score ( p < 0.001, r = 0.709). The univariate analysis based on 1.2 of PT-INR indicated statistical differences in most categories of ROTEM, which is similar to analysis performed for the presence and absence of T-DIC. Conclusions: Among JAAM DIC criteria, the PT-INR ≥1.2 was the most accurate factor for both the diagnosis of T-DIC and the evaluation of its severity. [ABSTRACT FROM AUTHOR]

Background: Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy. Methods: We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed. Results: We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients. Conclusions: Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test nickel titanium (NiTi) instrument performance under different surrounding temperatures. Twenty-four superelastic NiTi instruments with a conical shape comprising a 0.30-mm-diameter tip and 0.06 taper were equally divided into 3 groups according to the temperature employed. Using a specially designed cyclic fatigue testing apparatus, each instrument was deflected to give a curvature 10 mm in radius and a 30° angle. This position was kept as the instrument was immersed in a continuous flow of water under a temperature of 10, 37, or 50 °C for 20 s to calculate the deflecting load (DL). In the same position, the instrument was then allowed to rotate at 300 rpm to fracture, and the working time was converted to the number of cycles to fracture (NCF). The statistical significance was set at p = 0.05. The mean DL (in N) and NCF (in cycles) of the groups at 10, 37, and 50 °C were 10.16 ± 1.36 and 135.50 ± 31.48, 13.50 ± 0.92 and 89.20 ± 16.44, and 14.70 ± 1.21 and 65.50 ± 15.90, respectively. The group at 10 °C had significantly the lowest DL that favorably resulted in the highest NCF. Within the limitations of this study, the surrounding temperature influences the cyclic fatigue resistance and DL of the superelastic NiTi instruments. Lower temperatures are found to favorably decrease the DL and extend the lifetime of the superelastic NiTi instrument. Further NiTi instrument failure studies should be performed under simulated body temperature. [ABSTRACT FROM AUTHOR]

There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients. [ABSTRACT FROM AUTHOR]

Background: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. Methods: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with 'no vomiting', 'no significant nausea', and complete response, respectively. Results: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of 'no vomiting' patients (78.2 vs. 54.8 %; P < 0.0001), 'no significant nausea' patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group. Conclusion: The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy. [ABSTRACT FROM AUTHOR]

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using 1H-magnetic resonance spectroscopy (1H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and 1H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC. [ABSTRACT FROM AUTHOR]