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Aims: p16 is a sensitive surrogate marker for transcriptionally active high‐risk human papillomavirus (HR‐HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect. Methods and results: We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR‐HPV infection by mRNA in‐situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR‐HPV was detected in 83 of 108 ECA cases (77%), including five HPV‐associated adenocarcinomas in situ and 78 invasive HPV‐associated adenocarcinomas. All 83 HPV‐positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV‐independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV‐independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR‐HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR‐HPV infection correlated with better prognosis among invasive ECAs. Conclusions: The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR‐HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy. [ABSTRACT FROM AUTHOR]

Guangnanmycin A is a recently discovered congener of the well‐known antitumor drug lead leinamycin; its macrolactam ring, however, is even more strained than that of the parent compound. The first synthetic foray towards this challenging target is reported, which relies on molybdenum‐catalyzed macrocyclization by ring closing alkyne metathesis (RCAM) followed by ruthenium‐catalyzed redox isomerization of the propargyl alcohol thus formed; the resulting enone enabled the introduction of the yet missing exo‐methylene group by a modified Peterson olefination. The signature disulfide moiety of guangnanmycin A was installed by strain‐driven thia‐Michael addition followed by conversion of the thioether thus formed into an unsymmetric disulfide with the aid of (methylthio)dimethylsulfonium tetrafluoroborate and MeSSMe. While this sequence furnished racemic guangnanmycin A alcohol in good overall yield, the final oxidation to the corresponding acid failed, most likely because of the exceptional sensitivity of the strained scaffold. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the optimal sodium hypochlorite solution (NaOCl) concentration to effectively remove the root canal biofilm without stimulating periradicular inflammation using coronal laser‐activated irrigation (CLAI). To compare the efficacy of different NaOCl concentrations combined with CLAI in removing the biofilm, an in vivo intraradicular biofilm rat model was used. Root canals were irrigated using an Er:YAG laser with either 5% or 0.5% NaOCl. Biofilm removal efficacy of CLAI was compared to that of conventional needle irrigation using scanning electron microscopy (SEM) and quantitative polymerase chain reaction (qPCR). Histological observation of CLAI‐associated periradicular inflammation was also conducted. In both the 5% and 0.5% CLAI groups, SEM observation showed the opening of the dentin tubules and biofilm removal. qPCR analysis indicated that the residual bacteria counts after cleaning were significantly lower in the 5% and 0.5% CLAI groups than in the conventional needle irrigation and positive control groups (Tukey test, p < 0.05), and no significant difference was observed between the 5% and 0.5% CLAI groups (p > 0.05). Periapical inflammation in the 5% CLAI group revealed the most severe, including significant neutrophilic and lymphocytic infiltration with abscess formation, while only mild vasodilation was observed in the 0.5% CLAI group. CLAI can remove the biofilm independently of chemical action, which avoids the risks associated with high NaOCl concentrations. Therefore, this root canal irrigation technique ensures safety and effectiveness, promising to contribute to new treatment strategies intended to remove intraradicular biofilm. [ABSTRACT FROM AUTHOR]

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high‐grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population‐based cancer registry, the incidence of ICC among young women aged 20–29 years showed a significant decline from 3.6 to 2.8 per 100 000 women‐years during 2016–2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20–29 years also decreased from 256 cases to 135 cases during 2011–2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20–29 years during 2017–2022 (90.5%–64.7%, p = 0.05; Cochran–Armitage trend test). This is the first report to suggest population‐level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) with near‐infrared (NIR) fluorescence imaging is used for lymphatic mapping. However, binding of ICG to blood proteins like serum albumin can shorten its retention time in sentinel lymph nodes (SLNs). Here, we investigated the efficacy and safety of a new fluorescence tracer comprising phytate and liposome (LP)‐encapsulated ICG. Coadministration of phytate with LP containing phosphatidic acid promotes chelation mediated by Ca2+ in bodily fluids to enhance SLN retention. Uniformly sized LPs (100 nm) encapsulating ICG under conditions that minimized fluorescence self‐quenching during storage were produced. We analyzed the behavior of the new tracer (ICG‐phytate‐LP) and control tracers (ICG and ICG‐LP) in the lymphatic flow of mice in terms of lymph node retention time. We also tested lymphatic flow and safety in pigs that have a more human‐like lymphatic system. LPs encapsulating stabilized ICG were successfully prepared. Mixing LP with phytate in the presence of Ca2+ increased both the particle size and negative surface charge. In mice, ICG‐phytate‐LP had the best lymph node retention, with a fluorescence intensity ratio that increased over 6 h and then decreased slowly over the next 24 h. In pigs, administration of ICG and ICG‐phytate‐LP resulted in no death or weight loss. There were no obvious differences between blood test results for the ICG and ICG‐phytate‐LP groups, and the overall safety was good. ICG‐phytate‐LP may be a useful new tracer for gynecological cancers that require time for lymph node identification due to a retroperitoneal approach. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis. To clarify the epidemiology of HEV and characterize the genetic diversity of the virus in Japan, nationwide enhanced surveillance and molecular characterization studies of HEV in Japan were undertaken from 2014 to 2021. In total, 2770 hepatitis E cases were reported, of which 88% were domestic cases, while only 4.1% represented cases following infection abroad. In addition, 57% of domestic infections occurred in males aged in their 40s–70s. For domestic cases, infection via pork meat consumption continued to be the most reported route. Analysis of the 324 sequences detected between 2016 and 2021 showed that the majority of domestic HEV strains belong to Genotype 3a (G3a) and G3b. In contrast, six of eight cases of G1 HEV reflected infection abroad. Our results suggest that HEV is circulating widely in Japan, with genotypes G3a and G3b being most prevalent. Continued surveillance is necessary to monitor future trends and changes in the epidemiology of HEV in Japan. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of in‐person attendance at an academic conference held during the Covid‐19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid‐19 virus. Methods: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7. Results: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in‐person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167–0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229–0.690, p = 0.0010]). Conclusion: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in‐person attendance at the congress. [ABSTRACT FROM AUTHOR]

Aim: Westernization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic‐assisted surgery according to whether patients are obese, morbidly obese, or nonobese. Methods: Sixty‐three patients with endometrial cancer who underwent robotic‐assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) <30 (group A, nonobese, n = 40), ≥30 and <35 (group B, obese, n = 13), or ≥35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated. Results: Conversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between‐group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2–29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19–46). Conclusion: Patients with endometrial cancer who are obese can be treated safely by robotic‐assisted surgery with a low risk of complications and few relapses. [ABSTRACT FROM AUTHOR]

Aim: Recently, a machine‐learning (ML) technique has been used to create generalizable classifiers for psychiatric disorders based on information of functional connections (FCs) between brain regions at resting state. These classifiers predict diagnostic labels by a weighted linear sum (WLS) of the correlation values of a small number of selected FCs. We aimed to develop a generalizable classifier for gambling disorder (GD) from the information of FCs using the ML technique and examine relationships between WLS and clinical data. Methods: As a training dataset for ML, data from 71 GD patients and 90 healthy controls (HCs) were obtained from two magnetic resonance imaging sites. We used an ML algorithm consisting of a cascade of an L1‐regularized sparse canonical correlation analysis and a sparse logistic regression to create the classifier. The generalizability of the classifier was verified using an external dataset. This external dataset consisted of six GD patients and 14 HCs, and was collected at a different site from the sites of the training dataset. Correlations between WLS and South Oaks Gambling Screen (SOGS) and duration of illness were examined. Results: The classifier distinguished between the GD patients and HCs with high accuracy in leave‐one‐out cross‐validation (area under curve (AUC = 0.89)). This performance was confirmed in the external dataset (AUC = 0.81). There was no correlation between WLS, and SOGS and duration of illness in the GD patients. Conclusion: We developed a generalizable classifier for GD based on information of functional connections between brain regions at resting state. [ABSTRACT FROM AUTHOR]

The present study compared a 3‐s isometric maximal voluntary contraction (MVC), concentric MVC and eccentric MVC of the elbow flexors performed daily for 5 days a week for 4 weeks for changes in muscle strength and thickness. Young sedentary individuals were assigned to one of three training groups (n = 13 per group) that performed either 3‐s isometric, concentric, or eccentric MVC once a day for 20 days, or to a control group (n = 10) that had measurements without training. The participants in the isometric group performed isometric MVC at 55° (0.96 rad) elbow flexion, and those in the concentric or eccentric group performed concentric MVC or eccentric MVC between 10° (0.17 rad) and 100° (1.75 rad) elbow flexion at 30°/s (0.52 rad/s) on an isokinetic dynamometer. MVC isometric torque at 20° (0.35 rad), 55° (0.96 rad), and 90° (1.57 rad) elbow flexion, MVC concentric and eccentric torque at 30°/s (0.52 rad/s) and 180°/s (3.14 rad/s), and muscle thickness (MT) of biceps brachii and brachialis were measured before and several days after the 20th exercise session. The control group did not show any changes. The eccentric group showed increases (p < 0.01) in isometric (three angle average: 10.2 ± 6.4%), concentric (two velocity average: 12.8 ± 9.6%), and eccentric MVC torque (12.2 ± 7.8%). An increase (p < 0.05) was limited for isometric MVC torque (6.3 ± 6.0%) in the concentric group, and for eccentric MVC torque (7.2 ± 4.4%) in the isometric group. No significant changes in MT were evident for all groups. Performing one 3‐s MVC a day increased muscle strength, but eccentric MVC produced more potent effects than isometric or concentric MVC. [ABSTRACT FROM AUTHOR]

Aim: The subterranean tissues of Panax ginseng, especially the root, have long been used in traditional Asian medicine. In traditional medicine, various formulas contain ginseng to relieve fatigue, improve splenic function, and strengthen immunity, while recent studies have reported many additional benefits, including improvement of Alzheimer's dementia. Multiple ginsenosides, polyacetylenes, and polysaccharides in ginseng root and rhizome contribute to these therapeutic activities. Most ginseng used today is cultivated and takes a long time to mature, so changes in the bioactive constituent profile with age could alter the potential health benefits. However, most studies on such age‐dependent changes in chemical composition have focused on ginsenosides. To examine the full spectrum of age‐dependent changes, the current study analyzed the contents of multiple secondary metabolites and primary metabolites in samples cultivated from one to five years. Methods: The contents of multiple secondary metabolites such as polyacetylenes and primary metabolites such as fatty acids, sugars, and phospholipids as well as ginsenosides were determined by liquid or gas chromatography–mass spectroscopy (LC/MS or GC/MS). Results: Ginsenoside Ro and 1,2‐dilinoleoyl‐sn‐glycero‐3‐phosphocholine increased substantially and progressively with number of years of cultivation. Other ginsenosides and sugars also increased with age, but with greater variability. Conversely, concentrations of falcarinol, fatty acids, and phosphatidic acid decreased with cultivation time. Conclusion: Cultivation years may influence the specific medicinal properties and other health benefits of ginseng preparations. [ABSTRACT FROM AUTHOR]

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12‐16 years, and catch‐up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2‐3 (CIN2‐3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine‐targeted types HPV16 or HPV18 to CIN2‐3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12‐15 years (n = 36), 16‐18 years (n = 23), 19–22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P <.001). This finding was supported by age at first sexual intercourse; among women with CIN2‐3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2‐3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P =.004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12‐14 years and catch‐up vaccination for adolescents aged 18 years and younger in Japan. [ABSTRACT FROM AUTHOR]

This clinical image presents a report on the diagnosis and treatment of anti‐NMDAR encephalitis, a rare disease. This report emphasizes the importance of a differential diagnosis for acute psychiatric symptoms. Accurate and timely diagnosis is critical for the selection and implementation of treatment and for optimal patient outcomes. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to characterise grade 1 (G1) endometrioid carcinoma in the elderly, by using clinicopathological features and immunohistochemical features of surrogate markers of molecular subtypes. Methods and results: We retrospectively analysed tumour samples from 268 patients with G1 endometrioid carcinoma (<40 years, n = 24; 40–59 years, n = 169; ≥60 years, n = 75) for whom long‐term clinical follow‐up data were available. G1 endometrioid carcinoma in the elderly (≥60 years) was characterised by frequent deep myometrial invasion, less frequent endometrioid intraepithelial neoplasia (EIN), lack of benign hyperplasia (BH), less frequent squamous differentiation, and occasional aberrant p53 expression. In contrast, this condition in the young (<40 years) was characterised by frequent EIN, BH, and squamous differentiation. Univariate analysis revealed that elderly status (≥60 years), International Federation of Obstetrics and Gynecology (FIGO) 2009 stage and aberrant p53 expression were significantly associated with shorter progression‐free survival, and multivariate analysis revealed that elderly status and FIGO 2009 stage were independently associated with a poor prognosis. Conclusions: G1 endometrioid carcinoma in the elderly is more aggressive than that in the young, and elderly status is an independent predictor of shorter progression‐free survival in this condition. We propose that type 1 tumours can be subdivided into type 1a (young age at onset and indolent) and type 1b (old age at onset and relatively aggressive). [ABSTRACT FROM AUTHOR]

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk‐reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results. [ABSTRACT FROM AUTHOR]

Direct nucleophilic substitution of alcohols with thiols or carbon nucleophiles was achieved using a mesoporous silica‐supported oxovanadium catalyst (VMPS4). Benzyl and allyl alcohols were compatible in this reaction under mild conditions, affording the products in high yields. The VMPS4 catalyst showed excellent chemoselectivity toward alcohols in the presence of acid‐labile functional groups, which is in contrast to that observed for the commonly used Lewis acid catalysts, which exhibit poor selectivity. The VMPS4 catalyst could be recycled by simple centrifugation, and the catalytic activity was maintained over seven cycles. [ABSTRACT FROM AUTHOR]

Cell‐free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell‐free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto μ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites. [ABSTRACT FROM AUTHOR]

Aim: PEGylated liposomal doxorubicin (PLD) is a therapeutic agent for gynecological malignancy. Hypersensitivity reaction (HSR) is a major adverse effect that usually disappears after halting administration of PLD. Premedication is usually not necessary before administration of PLD to prevent HSR. Here, we evaluated the frequency of HSR during administration of PLD following premedication in Japanese women. Methods: We performed PLD administration in 78 patients (386 cycles) between 2013 and 2018. Granisetron hydrochloride and dexamethasone sodium phosphate were administered 30 min before PLD administration. Then, PLD (40 or 30 mg/m2 combined usage with carboplatin) was administered. We retrospectively reviewed the medical records of 78 patients and examined the frequency of HSR. Results: Seven of 78 (9%) patients showed HSR by PLD administration following premedication. One patient showed cardiopulmonary arrest in 13 min after PLD administration (grade 4). The other six patients showed grade 2 HSR. All patients developed HSR in the first course. The incidence of HSR was significantly higher in patients with allergic history than in patients without allergic history (p = 0.0151). Conclusions: Clinicians should be aware of the potential for HSR in patients administered PLD, particularly those with allergic history and those receiving the first cycle of PLD, even following premedication. [ABSTRACT FROM AUTHOR]

The prognosis of patients with high‐grade or advanced‐stage endometrial cancer remains poor. As cancer stem‐like cells (CSCs) are thought to be associated with endometrial cancers, it is essential to investigate the molecular mechanisms that regulate endometrial CSCs. Dual‐specificity phosphatase 6 (DUSP6) functions as a negative‐feedback regulator of MAPK–ERK1/2 signaling, but its role in endometrial cancer remains unknown. We investigated whether DUSP6 is involved in cancer cell stemness using endometrial cancer cell lines and specimens from endometrial cancer patients. DUSP6 induced the expression of CSC‐related genes including ALDH1, Nanog, SOX2 and Oct4A, increased the population of cells in the G0/G1 phase, and promoted sphere formation ability. DUSP6 knockdown resulted in reduced cell invasion and metastasis, whereas DUSP6 overexpression inhibited apoptosis under serum‐free conditions. Moreover, DUSP6 decreased phosphorylated ERK1/2 and increased phosphorylated Akt levels, which potentially induces CSC features. In patients with endometrial cancers, DUSP6 expression was determined using immunohistochemistry, and based on the results, the patients were dichotomized into high‐ and low‐DUSP6‐expression groups. Progression‐free survival and overall survival were significantly shorter in the high‐DUSP6‐expression group. These results suggest that DUSP6 has potential value as a biomarker of CSCs and as a target of therapies designed to eliminate CSCs in endometrial cancer. What's new? Although cancer stem‐like cells (CSCs) are involved in human endometrial cancers, the underlying molecular mechanisms and biomarkers for CSCs in endometrial cancers remain elusive. Here, the authors found that DUSP6 plays an important role in regulating endometrial CSC phenotypes by increasing self‐renewal ability and starvation resistance. DUSP6 expression was required for inducing invasion and metastasis and resulted in ERK1/2 dephosphorylation and Akt phosphorylation, which potentially contribute to the promotion of CSC phenotypes. As DUSP6 expression was also positively associated with worse progression‐free and overall survival, DUSP6 represents a potential biomarker for endometrial CSCs and a therapeutic target in endometrial cancers. [ABSTRACT FROM AUTHOR]

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P <.0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the applicability of the Øie‐Tozer model to predict human distribution volume (Vd) in the central compartment (V1), Vd at steady state (Vdss), and Vd at beta phase (Vdβ) based on animal Vd. Twenty compounds that have a human V1/Vdss of 0.053–0.66 were selected from the literature. After intravenous administration of the compounds at 0.1 mg/kg to rats, dogs, and monkeys, plasma concentrations were determined, and pharmacokinetic parameters were obtained by one/two‐compartmental analyses. The human V1, Vdss, and Vdβ were predicted from animal Vd using the Øie‐Tozer model, and the predictability was compared with that using proportionality and simple allometry. The Øie‐Tozer model was the most reliable method for the overall prediction of Vd and applicable for accurately predicting human V1, Vdss, and Vdβ (89%, 85%, and 68% of the compounds within a 3‐fold error, respectively) when data of monkey for V1 and data of three animal species for Vdss and Vdβ were used. Additionally, the predicted human Vd with the two‐compartment model was applicable for predicting pharmacokinetic profiles/parameters in humans after intravenous administration of 18 compounds [except for valproic acid (monophasic elimination profile) and chlorpromazine (deviation: Vdss < V1)]. The prediction was more accurate than that using the predicted Vdss with the one‐compartment model (e.g., underestimation of maximum plasma concentrations: 2 vs 8 compounds within a 3‐fold error, respectively). In summary, the Øie‐Tozer model was applicable for predicting human V1, Vdss, and Vdβ, and their predicted Vd with the two‐compartment model can lead to accurate pharmacokinetic prediction of compounds that show biphasic elimination. [ABSTRACT FROM AUTHOR]

Aim: Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100 000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients. Methods: A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis. Results: The median patient age was 63 years (range, 35–83 years). The largest group of patients had stage IB disease (stage IB, n = 8; IIB, n = 2; IIIB, n = 1; IVB, n = 3) and the largest group by histological subtype was ordinary (ordinary, n = 11; myxoid, n = 2; epithelioid, n = 1). Total abdominal hysterectomy and bilateral salpingo‐oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5–75 months), and 11 patients were alive (without disease, n = 5; with disease, n = 6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease. Conclusion: ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease. [ABSTRACT FROM AUTHOR]

Aim: To evaluate how the desire to have children and engage in sexual activity change after trachelectomy in Japanese women with early‐stage cervical cancer who strongly desired to have children before surgery. Methods: Desire to have children, coital pain, fear of sexual intercourse, sexual activity frequency and libido were assessed in cervical cancer patients who received follow‐up after trachelectomy. An anonymous questionnaire survey was conducted via informed consent. Results: Of the 151 patients who underwent trachelectomy at Kyushu University Hospital between 2005 and 2015, 46 patients were evaluated; the response rate was 30%. The desire to have children disappeared in 13 of 46 (28%) patients, and 14 (30%) patients experienced increased coital pain. Moreover, 19 (41%) patients experienced fear of sexual intercourse, and sexual frequency decreased in 24 (52%) patients. Conclusion: Trachelectomy is an important fertility‐sparing surgical method; however, this study revealed loss of the desire to have children and/or to engage in sexual activity in some patients after surgery. Counseling about these issues is important and should be addressed. [ABSTRACT FROM AUTHOR]

Aim: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3‐deoxyglucosone (3‐DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. Methods: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3–5. At enrolment, MG, 3‐DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end‐stage renal disease. Survival analysis was performed using the Cox regression model. Results: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2, which negatively correlated with MG but not with 3‐DG and pentosidine. Forty‐eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71–33.54) in the middle tertile and 27.00 (CI: 6.46–112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37–11.96) and 6.13 (CI: 0.97–38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3‐DG and pentosidine were not related to the primary outcome. Conclusion: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis. SUMMARY AT A GLANCE: Higher plasma concentrations of methylglyoxal (MG), a marker of oxidative stress, were shown to correlate with the development of end‐stage kidney disease in patients with chronic kidney disease (CKD), especially those with diabetic kidney disease (DKD). MG may be a biomarker for progressive CKD and especially DKD. [ABSTRACT FROM AUTHOR]

The metabolism and pharmacokinetics of DSP‐0565 [2‐(2′‐fluoro[1,1′‐biphenyl]‐2‐yl)acetamide], an antiepileptic drug candidate, was investigated in rats, dogs, and humans. In human hepatocytes, [14C]DSP‐0565 was primarily metabolized via amide bond hydrolysis to (2′‐fluoro[1,1′‐biphenyl]‐2‐yl)acetic acid (M8), while in rat and dog hepatocytes, it was primarily metabolized via both hydrolysis to M8 and hydroxylation at the benzene ring or the benzyl site to oxidized metabolites. After single oral administration of [14C]DSP‐0565 to rats and dogs, the major radioactivity fraction was recovered in the urine (71–72% of dose) with a much smaller fraction recovered in feces (23–25% of dose). As primary metabolites in their excreta, M8, oxidized metabolites, and glucuronide of DSP‐0565 were detected. The contribution of metabolic pathways was estimated from metabolite profiles in their excreta: the major metabolic pathway was oxidation (57–62%) and the next highest was the hydrolysis pathway (23–33%). These results suggest that there are marked species differences in the metabolic pathways of DSP‐0565 between humans and animals. Finally, DSP‐0565 human oral clearance (CL/F) was predicted using in vitro–in vivo extrapolation (IVIVE) with/without animal scaling factors (SF, in vivo intrinsic clearance/in vitro intrinsic clearance). The SF improved the underestimation of IVIVE (fold error = 0.22), but the prediction was overestimated (fold error = 2.4–3.3). In contrast, the use of SF for hydrolysis pathway was the most accurate for the prediction (fold error = 1.0–1.4). Our findings suggest that understanding of species differences in metabolic pathways between humans and animals is important for predicting human metabolic clearance when using animal SF. [ABSTRACT FROM AUTHOR]

Programmed cell death ligand 1 (PD‐L1) on tumor cells suppresses anti‐tumor immunity and has an unfavorable prognostic impact in ovarian cancer patients. We herein report the pathophysiological and therapeutic impacts of PD‐L1 disruption in ovarian cancer. PD‐L1 was genetically disrupted in the murine ovarian cancer cell line ID8 using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9‐mediated genome editing. PD‐L1 knockout (KO) and control ovarian cancer cells were intraperitoneally inoculated into syngeneic mice, and survival and tumor dissemination were evaluated. Survival times were significantly longer in the PD‐L1‐KO ID8‐inoculated groups than in their control groups, and its therapeutic benefit was enhanced in combination with the cisplatin treatment. Tumor weights and ascites volumes were significantly lower in the PD‐L1‐KO ID8 groups than in their control groups. Immunohistochemical and immunofluorescence analyses showed that intratumoral CD4+ T cells, CD8+ T cells, NK cells and CD11c+ M1 macrophages were significantly increased, whereas regulatory T cells were significantly decreased in the PD‐L1‐KO ID8 groups compared with those in their control groups. The intratumoral mRNA expression of interferon‐γ, tumor‐necrosis factor‐α, interleukin (IL)‐2, IL‐12a, CXCL9 and CXCL10 was significantly stronger, while that of IL‐10, vascular endothelial growth factor, CXCL1 and CXCL2 was significantly weaker in the PD‐L1‐KO ID8 groups. These results indicate that CRISPR/Cas9‐mediated PD‐L1 disruption on tumor cells promotes anti‐tumor immunity by increasing tumor‐infiltrating lymphocytes and modulating cytokine/chemokine profiles within the tumor microenvironment, thereby suppressing ovarian cancer progression. These results suggest that PD‐L1‐targeted therapy by genome editing may be a novel therapeutic strategy for ovarian cancer. We established a programmed cell death ligand 1 (PD‐L1) knockout ovarian cancer cell line using the clustered regularly interspaced short palindromic repeats/Cas9 system. We demonstrated that the complete disruption of PD‐L1 on tumor cells promoted anti‐tumor immunity by increasing tumor‐infiltrating lymphocytes and modulating cytokine/chemokine production within the tumor microenvironment, thereby suppressing ovarian cancer progression. [ABSTRACT FROM AUTHOR]

Monodisperse silica particles (SiPs) were surface‐modified with a newly designed silane coupling agent comprising a triethoxysilane and an alkyl halide, namely, 6‐(triethoxysilyl)hexyl 2‐bromopropionate, which was further treated with potassium O‐ethyl dithiocarbonate (PEX) to immobilize xanthate molecules on the particle surfaces. Surface‐initiated macromolecular design via interchange of xanthates (MADIX) polymerization of vinyl acetate (VAc) was conducted with the xanthate‐functionalized SiPs. The polymerization was well controlled and produced SiPs coated with poly(vinyl acetate) (PVAc) with a well‐defined target molar mass and a graft density of about 0.2 chains nm−2. Dynamic light scattering and TEM measurements revealed that the hybrid particles were highly dispersible in good solvents without any aggregation. The PVAc brushes were hydrolyzed with hydrochloric acid to produce poly(vinyl alcohol) brushes on the SiP surfaces. In addition, the number of xanthate molecules introduced on the SiP surfaces could be successfully controlled by adjusting the concentration of PEX. Thus, the SiPs have two functionalities: xanthates able to act as a MADIX chain‐transfer agent and alkyl bromide initiation sites for atom transfer radical polymerization (ATRP). By using these unique bifunctional particles, mixed polymer brushes were constructed on the SiPs by MADIX of VAc followed by ATRP of styrene or methyl methacrylate. Well brushed: Surface‐initiated polymerization of vinyl acetate from xanthate‐modified silica particles resulted in hybrid particles grafted with well‐defined poly(vinyl acetate) brushes (see scheme). Hydrolysis of the poly(vinyl acetate) brushes generated the first well‐defined, concentrated poly(vinyl alcohol) brushes. A strategy for fabricating mixed polymer brushes was also developed. [ABSTRACT FROM AUTHOR]

Aim: Only a few reports of pelvic abscess as a late complication of trachelectomy have been published to date. To evaluate the cases of pelvic abscess as a late complication of abdominal trachelectomy for cervical cancer. Methods: In June 2005, we began a clinical trial of abdominal trachelectomy at our institution. Written informed consent was obtained from all patients. We retrospectively reviewed the medical records of patients who underwent trachelectomy and extracted the data of patients who experienced pelvic abscess as a late complication. Results: From June 2005 to September 2017, we performed 181 trachelectomies at our institution. In total, 15 pelvic abscesses occurred in 12 of these patients more than 1 month after trachelectomy. The median postoperative period before the onset of pelvic abscess was 51 months (range, 1−104 months). Among the 15 cases, abscess formed in the uterine adnexa in 12, in a pelvic lymphocyst in two, and in the uterus in one. Abscess drainage was performed in six cases. Three patients underwent laparotomy with salpingo‐oophorectomy. Conclusion: It is possible that not only surgical removal of the uterine cervix but also the use of nonabsorbable suture in cervical cerclage and placement of an intrauterine device triggered post‐trachelectomy infection. Pelvic abscess can occur as a late complication of abdominal trachelectomy. [ABSTRACT FROM AUTHOR]

Introduction: Despite numerous reports on pregnancy outcomes after trachelectomy, there are few descriptions of fertility treatment after trachelectomy. Moreover, little is known about the differences in fertility outcomes between various radical trachelectomy procedures. The purpose of this report was to clarify the infertility problems that occur in patients who have previously undergone an abdominal trachelectomy.Material and Methods: We retrospectively investigated the medical records of 37 patients who received fertility treatments or were evaluated for menstrual disorders after trachelectomies in our institution between 2012 and 2016.Results: Twenty-two of 37 patients had complications which affected fecundity. Six patients had cervical stenosis requiring surgical dilation, 4 had ovarian insufficiency, and 14 had Asherman's syndrome.Conclusions: In spite of efforts to preserve fertility, some patients have severe complications after trachelectomy, such as Asherman's syndrome, resulting in infertility. Clinicians should pay careful attention to the status of the endometrial cavity after trachelectomy. [ABSTRACT FROM AUTHOR]

Abstract: Background: We compared the quality of care for nursing‐ and healthcare‐associated pneumonia (NHCAP) and aspiration pneumonia provided by general physicians and pulmonologists. Methods: Questionnaires were mailed to 2490 medical facilities across Japan. The questionnaire assessed participants’ implementation of microbiological investigations for NHCAP or aspiration pneumonia, as well as steps taken to prevent pneumonia recurrence (eg, use or discontinuation of drugs associated with swallowing and administration of pneumococcal polysaccharides). Survey results were statistically compared between the two groups using chi‐square tests. Results: We received responses from 350 hospitals; of those, medical care for aspiration pneumonia was provided by pulmonologists at 190 hospitals and by general physicians at 79 hospitals. No significant differences were observed between the two groups of physicians for any of the items regarding proactive microbiological investigations or measures for preventing pneumonia recurrence. However, general physicians tended to be more proactive in conducting Gram's stains for sputum, sputum culture inspections, and blood culture tests. They also were more likely to implement measures for preventing pneumonia recurrence such as striving to increase patients’ consciousness levels, reducing medication doses, and discontinuing drugs that cause difficulty with swallowing (response rates of “is done in nearly all cases” were 73.4%, 88.6%, 36.7%, 35.4%, and 40.5%, respectively). Conclusions: The quality of care provided by general physicians may be on par with pulmonologists in terms of proactive microbiological investigations and preventing pneumonia recurrence. [ABSTRACT FROM AUTHOR]

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Abstract: Aim: To investigate the surgical outcome of FIGO stage IA1 cervical adenocarcinoma. Methods: Between 2005 and 2011, 12 patients from Kyushu University Hospital had cervical adenocarcinoma, with a tumor depth of less than 3 mm and a horizontal width of less than 7 mm (FIGO stage IA1), diagnosed by cervical conization. All patients underwent simple hysterectomy or simple trachelectomy with pelvic lymphadenectomy. Results: The mean patient age was 34 years (range, 26–70 years). The median follow‐up period was 70.5 months (range, 26–99 months). No pelvic lymph‐node metastasis was seen, and no patient experienced disease recurrence. Conclusion: Early invasive cervical adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread of 7 mm or less has little potential for nodal metastasis or recurrence. Therefore, simple hysterectomy or trachelectomy, without lymphadenectomy, might be an alternative treatment option for stage IA1 cervical adenocarcinoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the apical centring ability of incisal-shifted access ( ISA) with that of traditional lingual access ( TLA). Fifteen three-dimensional printed resin models were prepared from the computed tomography data for a human maxillary central incisor and divided into ISA ( n = 7), TLA ( n = 7) and control ( n = 1) groups. After access preparation, these models were shaped to the working length using K-files up to #40, followed by step-back procedures. An apical portion of the model was removed at 0.5 mm coronal to the working length. Microscopic images of each cutting surface were taken to measure the preparation area and the distance of transportation. TLA created a larger preparation area than ISA ( P < 0.05). The distance of transportation (mean ± standard deviation) was 0.4 ± 0.1 mm for ISA and 0.7 ± 0.1 mm for TLA ( P < 0.05). Access cavity preparation has a significant effect on apical centring ability. ISA is beneficial to maintaining apical configuration. [ABSTRACT FROM AUTHOR]

Aim We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. Methods We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE]). All sera were obtained within 1 week prior to delivery, and soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured with enzyme-linked immunosorbent assay. Results (i) In PE, a significantly increased sFlt-1, sEng, and sFlt-1 to PlGF ratio (sFlt-1/PlGF) and significantly decreased PlGF were observed compared with GH and Term control, whereas in GH, only sFlt-1/PlGF was significantly higher than Term control. (ii) In PE + FGR, similar changes were more markedly shown compared with PE alone. The FGR alone group exhibited similar tendencies as PE, although significant differences were found in PlGF and sEng levels. (iii) In EO PE, significant changes were observed in all factors compared with LO PE or Term control, while no significant change in PlGF levels was observed between LO PE and Term control. Conclusion We demonstrated that the levels of circulating angiogenic factors just before delivery are correlated with the severity of hypertensive disorders of pregnancy and FGR. Profiling these specific markers may contribute to better understanding of the clinical conditions in individual patients and their pathogenesis. [ABSTRACT FROM AUTHOR]

Adult bone mass is maintained through a balance of the activities of osteoblasts and osteoclasts. Although Notch signaling has been shown to maintain bone homeostasis by controlling the commitment, differentiation, and function of cells in both the osteoblast and osteoclast lineages, the precise mechanisms by which Notch performs such diverse and complex roles in bone physiology remain unclear. By using a transgenic approach that modified the expression of delta-like 1 ( DLL1) or Jagged1 ( JAG1) in an osteoblast-specific manner, we investigated the ligand-specific effects of Notch signaling in bone homeostasis. This study demonstrated for the first time that the proper regulation of DLL1 expression, but not JAG1 expression, in osteoblasts is essential for the maintenance of bone remodeling. DLL1-induced Notch signaling was responsible for the expansion of the bone-forming cell pool by promoting the proliferation of committed but immature osteoblasts. However, DLL1-Notch signaling inhibited further differentiation of the expanded osteoblasts to become fully matured functional osteoblasts, thereby substantially decreasing bone formation. Osteoblast-specific expression of DLL1 did not alter the intrinsic differentiation ability of cells of the osteoclast lineage. However, maturational arrest of osteoblasts caused by the DLL1 transgene impaired the maturation and function of osteoclasts due to a failed osteoblast-osteoclast coupling, resulting in severe suppression of bone metabolic turnover. Taken together, DLL1-mediated Notch signaling is critical for proper bone remodeling as it regulates the differentiation and function of both osteoblasts and osteoclasts. Our study elucidates the importance of ligand-specific activation of Notch signaling in the maintenance of bone homeostasis. J. Cell. Physiol. 232: 2569-2580, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc. [ABSTRACT FROM AUTHOR]

Unified, efficient, and scalable syntheses of the halichondrin natural products are reported. A newly developed Zr/Ni-mediated one-pot ketone synthesis was used to couple the two halves of the final product at a late stage in the synthesis. With the use of a slight excess of the left halves, the desired ketones were isolated in yields of 80-90 %. The halichondrins were obtained from these ketones in two steps, namely desilylation and [5,5]-spiroketal formation. The new synthetic route was effective for the total synthesis of all members in the homohalichondrin subgroup. The scalability of this process was demonstrated with halichondrin B; 150 mg of halichondrin B (68 % overall yield) were obtained from 200 mg of the right-half precursor. [ABSTRACT FROM AUTHOR]

A zirconium/nickel-mediated one-pot synthesis of ketones is reported. In the presence of Zn or Mn, Cp2ZrCl2 was found to dramatically accelerate the coupling and suppress side product formation via an I→SPy displacement at the same time. Unlike Zn/Pd- and Fe/Cu-mediated one-pot ketone syntheses, the new method is effective for nucleophiles bearing OR or equivalent functional groups at the α-position. A mechanism comprising a nickel catalytic cycle, a zirconium catalytic cycle, and Zr→Ni transmetalation is proposed, and Cp2ZrCl2 and/or low-valent Zr species are suggested to play crucial dual roles. [ABSTRACT FROM AUTHOR]

Psychiatry research has long experienced a stagnation stemming from a lack of understanding of the neurobiological underpinnings of phenomenologically defined mental disorders. Recently, the application of computational neuroscience to psychiatry research has shown great promise in establishing a link between phenomenological and pathophysiological aspects of mental disorders, thereby recasting current nosology in more biologically meaningful dimensions. In this review, we highlight recent investigations into computational neuroscience that have undertaken either theory- or data-driven approaches to quantitatively delineate the mechanisms of mental disorders. The theory-driven approach, including reinforcement learning models, plays an integrative role in this process by enabling correspondence between behavior and disorder-specific alterations at multiple levels of brain organization, ranging from molecules to cells to circuits. Previous studies have explicated a plethora of defining symptoms of mental disorders, including anhedonia, inattention, and poor executive function. The data-driven approach, on the other hand, is an emerging field in computational neuroscience seeking to identify disorder-specific features among high-dimensional big data. Remarkably, various machine-learning techniques have been applied to neuroimaging data, and the extracted disorder-specific features have been used for automatic case-control classification. For many disorders, the reported accuracies have reached 90% or more. However, we note that rigorous tests on independent cohorts are critically required to translate this research into clinical applications. Finally, we discuss the utility of the disorder-specific features found by the data-driven approach to psychiatric therapies, including neurofeedback. Such developments will allow simultaneous diagnosis and treatment of mental disorders using neuroimaging, thereby establishing 'theranostics' for the first time in clinical psychiatry. [ABSTRACT FROM AUTHOR]

Gestational choriocarcinoma metastasizing to the bones, especially to the spine, is extremely rare. In addition, there are few reports of choriocarcinoma during a viable pregnancy. We report a case of gestational choriocarcinoma that metastasized to the lumbar spine during a viable pregnancy in a 41-year-old woman with a history of a missed abortion. A heterogeneous cervical mass was detected at gestational week 16. Subsequently, a metastatic lesion appeared during the pregnancy, and fetal demise in utero occurred. Pathological examination revealed that the cervical tumor and metastatic spinal tumor were choriocarcinoma. The patient's condition deteriorated rapidly and we were unable to save her life, despite multidrug chemotherapy. Surgical tumor resection and pregnancy might involve a substantial risk of choriocarcinoma metastasis. It is important to obtain an early diagnosis for this life-threatening disease in order to facilitate appropriate treatment, despite pregnancy. [ABSTRACT FROM AUTHOR]

ABSTRACT Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017. [ABSTRACT FROM AUTHOR]

Aim Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. Methods We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant ( n = 24) received either correct or incorrect ( Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. Results Under correct feedback conditions, significant activation was observed in the frontal pole cortex ( P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals ( P = 0.006). Conclusion The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation. [ABSTRACT FROM AUTHOR]

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake ( SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. [ABSTRACT FROM AUTHOR]

Cytological diagnosis after trachelectomy is challenging. Sharing information can help cytopathologists and gynecologic oncologists to acquire sufficient information and to provide patients with appropriate care. [ABSTRACT FROM AUTHOR]

Background Anti-platelet therapy for Kawasaki disease ( KD) is often done without monitoring drug efficacy. The aim of this study was to investigate the utility of whole-blood aggregometry to evaluate the efficacy of anti-platelet therapy for KD. Methods Of 37 late-phase KD patients included in the present study, 20 were prescribed anti-platelet drugs. Platelet-rich plasma ( PRP) aggregation with collagen as the stimulus was measured using an optical aggregometer. The area under the curve of small and large size aggregations was calculated, and categorized into five classes: -2, -1, 0, 1, and 2. Whole-blood aggregation with collagen or adenosine 5′-diphosphate ( ADP) as stimulus was evaluated using the platelet aggregation threshold index ( PATI), which is the concentration of stimulus that induces a whole-blood aggregation rate of 50%. Results In both collagen- and ADP-induced aggregation, there was a negative correlation between PATI and class determination using the PRP technique (collagen, rs = −0.870, P < 0.0001; ADP, rs = −0.620, P < 0.0001). Moreover, the PATI in collagen- and ADP-induced aggregation was significantly higher in the anti-platelet drug therapy group than in the untreated group (collagen, P < 0.0001; ADP, P = 0.0002). The serum thromboxane B2 level in the anti-platelet drug therapy group was also significantly lower than that in the untreated group ( P < 0.0001). PATI was significantly higher in those treated with thienopyridine drug combinations than those without drug therapy ( P = 0.0036). Conclusions Whole-blood aggregometry is useful for monitoring the efficacy of anti-platelet therapy for KD. [ABSTRACT FROM AUTHOR]