Japanese survey of perioperative complications and ureteral stricture after ureteroscopy with laser lithotripsy for upper urinary tract stones in multicenter collaborative study.

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.

Two cases of prostate cancer with disseminated carcinomatosis of the bone marrow treated with novel hormonal agents.

Introduction: Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear. Case presentation: We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis. One patient was treated with enzalutamide, abiraterone, docetaxel, cabazitaxel, denosumab, and radium-223 and died 38 months after the initial diagnosis. The other patient was treated with apalutamide and denosumab, and had progression-free survival for 17 months after the initial diagnosis. Conclusion: These results suggest that novel hormonal agents may improve the prognosis of prostate cancer even in patients with disseminated carcinomatosis of the bone marrow.

The neural circuit linking mushroom body parallel circuits induces memory consolidation in Drosophila.

Memory consolidation is augmented by repeated learning following rest intervals, which is known as the spacing effect. Although the spacing effect has been associated with cumulative cellular responses in the neurons engaged in memory, here, we report the neural circuit-based mechanism for generating the spacing effect in the memory-related mushroom body (MB) parallel circuits in Drosophila To investigate the neurons activated during the training, we monitored expression of phosphorylation of mitogen-activated protein kinase (MAPK), ERK [phosphorylation of extracellular signal-related kinase (pERK)]. In an olfactory spaced training paradigm, pERK expression in one of the parallel circuits, consisting of γm neurons, was progressively inhibited via dopamine. This inhibition resulted in reduced pERK expression in a postsynaptic GABAergic neuron that, in turn, led to an increase in pERK expression in a dopaminergic neuron specifically in the later session during spaced training, suggesting that disinhibition of the dopaminergic neuron occurs during spaced training. The dopaminergic neuron was significant for gene expression in the different MB parallel circuits consisting of α/ßs neurons for memory consolidation. Our results suggest that the spacing effect-generating neurons and the neurons engaged in memory reside in the distinct MB parallel circuits and that the spacing effect can be a consequence of evolved neural circuit architecture.

Inhibiting Glutamate Activity during Consolidation Suppresses Age-Related Long-Term Memory Impairment in Drosophila.

In Drosophila, long-term memory (LTM) formation requires increases in glial gene expression. Klingon (Klg), a cell adhesion molecule expressed in both neurons and glia, induces expression of the glial transcription factor, Repo. However, glial signaling downstream of Repo has been unclear. Here we demonstrate that Repo increases expression of the glutamate transporter, EAAT1, and EAAT1 is required during consolidation of LTM. The expressions of Klg, Repo, and EAAT1 decrease upon aging, suggesting that age-related impairments in LTM are caused by dysfunction of the Klg-Repo-EAAT1 pathway. Supporting this idea, overexpression of Repo or EAAT1 rescues age-associated impairments in LTM. Pharmacological inhibition of glutamate activity during consolidation improves LTM in klg mutants and aged flies. Altogether, our results indicate that LTM formation requires glial-dependent inhibition of glutamate signaling during memory consolidation, and aging disrupts this process by inhibiting the Klg-Repo-EAAT1 pathway.

Detection rate of clinically significant prostate cancer in magnetic resonance imaging and ultrasonography-fusion transperineal targeted biopsy for lesions with a prostate imaging reporting and data system version 2 score of 3-5.

OBJECTIVES: To evaluate the detection rates of clinically significant prostate cancer classified according to the prostate imaging reporting and data system scoring system using magnetic resonance imaging/ultrasound rigid fusion targeted biopsy. METHODS: A total of 339 patients underwent transperineal magnetic resonance imaging/ultrasound rigid fusion targeted biopsy in our institution between January 2015 and July 2017. Patients with prostate imaging reporting and data system category 1 or 2 and those with a pre-biopsy prostate-specific antigen value of >30 ng/mL were excluded from this study. Finally, 310 patients were recruited. RESULTS: The detection rates of clinically significant prostate cancer with prostate imaging reporting and data system category 3, 4, and 5 were 1.0% (1/98), 35.1% (47/134) and 73.1% (57/78), respectively. The factors affecting the detection of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5 were: (i) prostate imaging reporting and data system category 5; (ii) prostate volume <40 cc; (iii) no previous biopsy; (iv) lesion located in the peripheral zone; and (v) prostate-specific antigen density >0.35 ng/mL/mL. CONCLUSIONS: The detection rate of clinically significant prostate cancer on magnetic resonance imaging/ultrasound rigid fusion targeted biopsy is very low in patients with prostate imaging reporting and data system category 3; therefore, patients with this classification should not undergo targeted biopsy. Prostate-specific antigen density, prostate volume, locations of suspected cancer and history of biopsy should be considered to predict the detection rate of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5.

Postpartum depression among women in Nagoya indirectly exposed to the Great East Japan Earthquake.

This study aimed to assess the situation of postpartum depression and maternal bonding in Nagoya, a city distant from the epicenter of the Great East Japan Earthquake that occurred on March 11, 2011. Among the participants at 1 month after childbirth between March 11, 2010 and March 10, 2013 (n = 188), 152 fully responded to the Edinburgh Postnatal Depression Scale (EPDS) and Mother-Infant Bonding Questionnaire (MIBQ). They were divided into pre-quake (n = 58), and 0-6, 6-12, 12-18, and 18-24 months after the earthquake groups (n = 20, 26, 29, and 19, respectively). The rate of mothers who scored above the cutoff point for the EPDS increased from 12.1% in the pre-quake to 35.0% in the 0-6 months group (p = 0.022). The EPDS total and anxiety subscale scores (mean ± standard error) were also significantly different between the pre-quake and 0-6 months after the earthquake groups (4.45 ± 0.50 vs. 7.95 ± 1.47, p = 0.024; 2.16 ± 0.26 vs. 3.65 ± 0.57, p = 0.021, respectively). The EPDS total and anxiety scores were the highest for the 0-6 months group, followed by the 6-12, 12-18, 18-24 months groups (p = 0.019, p = 0.022). MIBQ scores did not differ between the pre-quake and 0-6 months groups. Depressive symptoms, mainly explained by anxiety, increased after the earthquake with no changes in maternal bonding.

Gastric neuroendocrine carcinoma with positive staining for prostate cancer markers including prostate-specific antigen and alpha-methylacyl-CoA racemase.

We report a case with prostate cancer and gastric neuroendocrine carcinoma. A 72-year old male presented with a gastric lesion 5 months after radical prostatectomy. The lesion was immunohistochemically positive for PSA, alpha-methylacyl-CoA racemase, synaptophysin, and chromogranin A, but negative for androgen receptor (AR). Differentiating gastric neuroendocrine carcinoma from gastric metastasis of prostate cancer is difficult, as both lesions exhibit similar acinar cell proliferation with prominent nucleoli.1 We discuss the diagnostic process of this case and how AR was a useful specific marker for diagnosing primary gastric neuroendocrine carcinoma.

A prospective study of magnetic resonance imaging and ultrasonography (MRI/US)-fusion targeted biopsy and concurrent systematic transperineal biopsy with the average of 18-cores to detect clinically significant prostate cancer.

BACKGROUND: This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. METHODS: This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. RESULTS: A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of <65 years were independent predictors for TB upgrading (vs. the SB result). CONCLUSIONS: PI-RADS v2 category 4 and an age of <65 years were predictive factors of upgrading the Gleason score by MRI/US-fusion TB. Thus, MRI/US-fusion TB may be appropriate for patients with those characteristics. TRIAL REGISTRATION: This study was retrospectively registered at the University Hospital Medical Information Network ( UMINID000025911 ) in Jan 30, 2017.

Social support helps protect against perinatal bonding failure and depression among mothers: a prospective cohort study.

Causal relationships between perinatal bonding failure, depression, and social support among mothers remain unclear. A total of 494 women (mean age 32.4 ± 4.5 years) completed the Mother-Infant Bonding Questionnaire (MIBQ), the Edinburgh Postnatal Depression Scale (EPDS), and the Japanese version of the Social Support Questionnaire in early pregnancy before week 25 (T1) and 1 month after delivery (T2). Our model of recursive structured equation modeling (SEM) showed acceptable fit (CMIN/df = 2.2, CFI = 0.97, and RMSEA = 0.05). It was revealed that: (1) a lower number of supportive persons at T1 significantly predicted both MIBQ and EPDS scores at T1 and T2; (2) at T1, poorer satisfaction with the social support received significantly predicted EPDS scores; (3) both MIBQ and EPDS scores at T1 significantly predicted their respective scores at T2. Out cohort study indicates that the number of individuals who are available to provide social support and the degree of satisfaction with the level of social support received during pregnancy have a great influence on bonding failure and depression in the postpartum period. These findings suggest that psychosocial interventions that focus on these two aspects of social support during pregnancy are effective in preventing bonding failure and depression in the postpartum period.

Relationship between maternal depression and bonding failure: A prospective cohort study of pregnant women.

AIM: Although the association between maternal depression and bonding failure during pregnancy and after delivery has been investigated, the causal relationships remain unclear. METHODS: A total of 751 women (mean [SD] age, 32.1 [4.4] years) completed the Mother-Infant Bonding Questionnaire and the Edinburgh Postnatal Depression Scale during early pregnancy before week 25 (T1), during late pregnancy around week 36 (T2), and at 5 days after delivery (T3). We created a structural regression model to clarify the relationships between depressive mood and bonding failure during pregnancy and at 5 days after delivery. The model was tested with structural equation modeling. RESULTS: Our non-recursive model fit the data well, and we found that: (i) during T2, bonding failure predicted depressive mood (P < 0.01, r = 0.23); (ii) at T3, bonding failure predicted depressive mood (P < 0.05, r = 0.31); (iii) during T1, depressive mood was correlated with bonding failure (P < 0.01, r = 0.45); (iv) depressive mood during T1 predicted depressive mood during T2 (P < 0.01, r = 0.58); (v) depressive mood during T2 predicted depressive mood at T3 (P < 0.01, r = 0.45); (vi) bonding failure during T1 predicted bonding failure during T2 (P < 0.01, r = 0.84); and (vii) bonding failure during T2 predicted bonding failure at T3 (P < 0.01, r = 0.44). The determinant coefficients of depressive mood and bonding failure at T3 were 0.41 and 0.28, respectively. CONCLUSION: Our large-scale cohort study indicates that bonding failure predicts depressive mood during pregnancy and 5 days after delivery. These findings suggest that protection and support for pregnant women with depressive mood and bonding failure may prevent both issues during pregnancy and the early stage after delivery.

Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies.

Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requires the CREB transcription factor and its coactivator, CBP, subsequent early maintenance requires CREB and a different coactivator, CRTC. Late maintenance becomes CREB independent and instead requires the transcription factor Bx. Bx expression initially depends on CREB/CRTC activity, but later becomes CREB/CRTC independent. The timing of the CREB/CRTC early maintenance phase correlates with the time window for LTM extinction and we identify different subsets of CREB/CRTC target genes that are required for memory maintenance and extinction. Furthermore, we find that prolonging CREB/CRTC-dependent transcription extends the time window for LTM extinction. Our results demonstrate the dynamic nature of stored memory and its regulation by shifting transcription systems in the MBs.

Validation and factor analysis of mother-infant bonding questionnaire in pregnant and postpartum women in Japan.

BACKGROUND: The Mother-Infant Bonding Questionnaire (MIBQ) has been widely used to assess maternal emotional involvement with infants. Although the reliability and validity of the MIBQ in the postpartum period has been confirmed, it remains unclear whether the MIBQ is appropriate to assess maternal bonding in both pregnancy and the postpartum period over time. Our study were aimed to 1) examine the reliability and validity of the MIBQ for clinical use among pregnant and postpartum women; and 2) examine the factor structure of the items, create subscales, and confirm the stability of the MIBQ in the pregnancy and postpartum periods. METHODS: Participants (n = 751, mean age 32.1 ± 4.4 years) completed the MIBQ and the Edinburgh Postnatal Depression Scale (EPDS) in early pregnancy (before week 25), in late pregnancy (around week 36), 5 days after delivery, and 1 month after delivery. We randomly divided participants into two sample sets. We conducted an exploratory factor analysis of the nine MIBQ items using data from one group of mothers (Group 1; n = 376) in all four periods. The factor structure derived from the exploratory factor analysis was confirmed by a confirmatory factor analysis in the second group (Group 2; n = 375) of mothers in all four periods. RESULTS: Exploratory factor analysis yielded two factors: Lack of Affection (LA) and Anger and Rejection (AR). Confirmatory factor analysis demonstrated that LA and AR factors existed for the MIBQ in all periods. Cronbach's alpha coefficients were 0.879 and 0.584, respectively. The scores for LA and AR were significantly correlated over the four time periods. Mothers with higher AR scores on the MIBQ at any of the four periods had higher scores on the EPDS. CONCLUSIONS: The MIBQ has two subscales regardless of the timing of the assessment. The MIBQ is appropriate for pregnant as well as postpartum women to assess maternal bonding toward the fetus and infant.

Nuclear hormone receptor LXRα inhibits adipocyte differentiation of mesenchymal stem cells with Wnt/beta-catenin signaling.

Nuclear hormone receptor liver X receptor-alpha (LXRα) has a vital role in cholesterol homeostasis and is reported to have a role in adipose function and obesity although this is controversial. Conversely, mesenchymal stem cells (MSCs) are suggested to be a major source of adipocyte generation. Accordingly, we examined the role of LXRα in adipogenesis of MSCs. Adult murine MSCs (mMSCs) were isolated from wild-type (WT) and LXR-null mice. Using WT mMSCs, we further generated cell lines stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) or GFP alone (mMSC/GFP) by retroviral infection. Confluent mMSCs were differentiated into adipocytes by the established protocol. Compared with MSCs isolated from WT mice, MSCs from LXR-null mice showed significantly increased adipogenesis, as determined by lipid droplet accumulation and adipogenesis-related gene expression. Moreover, mMSCs stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) exhibited significantly decreased adipogenesis compared with mMSCs overexpressing GFP alone (mMSC/GFP). Since Wnt/beta-catenin signaling is reported to inhibit adipogenesis, we further examined it. The LXR-null group showed significantly decreased Wnt expression accompanied by a decrease of cellular beta-catenin (vs WT). The mMSC/LXRα/GFP group exhibited significantly increased Wnt expression accompanied by an increase of cellular beta-catenin (vs mMSC/GFP). These data demonstrate that LXRα has an inhibitory effect on adipogenic differentiation in mMSCs with Wnt/beta-catenin signaling. These results provide important insights into the pathophysiology of obesity and obesity-related consequences such as metabolic syndrome and may identify potential therapeutic targets.

Relationship between social support during pregnancy and postpartum depressive state: a prospective cohort study.

Although the association between social support and postpartum depression has been previously investigated, its causal relationship remains unclear. Therefore, we examined prospectively whether social support during pregnancy affected postpartum depression. Social support and depressive symptoms were assessed by Japanese version of Social Support Questionnaire (J-SSQ) and Edinburgh Postnatal Depression Scale (EPDS), among 877 pregnant women in early pregnancy and at one month postpartum. First, J-SSQ was standardized among peripartum women. The J-SSQ was found to have a two-factor structure, with Number and Satisfaction subscales, by exploratory and confirmatory factor analyses. Analysis of covariance was performed to examine how EPDS and J-SSQ scores during pregnancy affected the EPDS score at postpartum. Significant associations were found between postpartum EPDS score and both EPDS and total scores on the Number subscales during pregnancy (ß = 0.488 and -0.054, ps < 0.001). Specifically, this negative correlation was stronger in depressive than non-depressive groups. Meanwhile, total score on Satisfaction subscales was not significantly associated with postpartum EPDS score. These results suggest that having a larger number of supportive persons during pregnancy helps protect against postpartum depression, and that this effect is greater in depressive than non-depressive pregnant women. This finding is expected to be vitally important in preventive interventions.

Preliminary report: nephroscope-assisted "pulling-thread" technique for placement of peritoneal dialysis catheter.

BACKGROUND: Several catheter placement procedures have been described for initiation of peritoneal dialysis, including percutaneous insertion, open surgery, and laparoscopic surgery. However, the optimal approach to catheter placement for peritoneal dialysis remains controversial, because each procedure has specific advantages and disadvantages. PATIENTS AND METHODS: From June 2010 to October 2014, we performed a nephroscope-assisted "pulling-thread" technique for placement of peritoneal dialysis catheters in 46 patients with end-stage renal disease at our medical center. We retrospectively reviewed the operation-related data, early catheter-related complications during the first month after placement, and longterm technical catheter survival. RESULTS: Catheters in all 46 patients were placed precisely in a single step during surgery. The mean operative time was 63.0±18.2 minutes, and no intra-operative complications occurred in any patient. Early catheter-related complications included only exit-site infection (n=2; 4.3%) and catheter obstruction (n=2; 4.3%). There was a mean follow-up period of 18.3±12.7 months. The probability of catheter survival at 1 year was 97.1% and at 2 years was 80.1%. CONCLUSION: Our technique has the advantages of simplicity, safety, minimal equipment, low early catheter- related complication rate, and favorable long-term catheter outcome, making it ideal for patients with end-stage renal disease.

Long-term memory formation in Drosophila requires training-dependent glial transcription.

Long-term memory (LTM) formation requires de novo gene expression in neurons, and subsequent structural and functional modification of synapses. However, the importance of gene expression in glia during this process has not been well studied. In this report, we characterize a cell adhesion molecule, Klingon (Klg), which is required for LTM formation in Drosophila. We found that Klg localizes to the juncture between neurons and glia, and expression in both cell types is required for LTM. We further found that expression of a glial gene, repo, is reduced in klg mutants and knockdown lines. repo expression is required for LTM, and expression increases upon LTM induction. In addition, increasing repo expression in glia is sufficient to restore LTM in klg knockdown lines. These data indicate that neuronal activity enhances Klg-mediated neuron-glia interactions, causing an increase in glial expression of repo. Repo is a homeodomain transcription factor, suggesting that further downstream glial gene expression is also required for LTM.

Glial dysfunction causes age-related memory impairment in Drosophila.

Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

Factor structure of the Japanese version of the Edinburgh Postnatal Depression Scale in the postpartum period.

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is a widely used screening tool for postpartum depression (PPD). Although the reliability and validity of EPDS in Japanese has been confirmed and the prevalence of PPD is found to be about the same as Western countries, the factor structure of the Japanese version of EPDS has not been elucidated yet. METHODS: 690 Japanese mothers completed all items of the EPDS at 1 month postpartum. We divided them randomly into two sample sets. The first sample set (n = 345) was used for exploratory factor analysis, and the second sample set was used (n = 345) for confirmatory factor analysis. RESULTS: The result of exploratory factor analysis indicated a three-factor model consisting of anxiety, depression and anhedonia. The results of confirmatory factor analysis suggested that the anxiety and anhedonia factors existed for EPDS in a sample of Japanese women at 1 month postpartum. The depression factor varies by the models of acceptable fit. CONCLUSIONS: We examined EPDS scores. As a result, "anxiety" and "anhedonia" exist for EPDS among postpartum women in Japan as already reported in Western countries. Cross-cultural research is needed for future research.

Effects of maternal depressive symptomatology during pregnancy and the postpartum period on infant-mother attachment.

AIM: Postnatal depression has demonstrated long-term consequences on child cognitive and emotional development; however, the link between maternal and child pathology has not been clearly identified. We conducted a prospective study using self-rating questionnaires to clarify the association between bonding disorder and maternal mood during pregnancy and after childbirth. METHODS: A total of 389 women participated in this study and completed questionnaires. Participants were asked to complete the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-to-Infant Bonding Scale four times during pregnancy and the postpartum period. RESULTS: We found statistically significant weak to moderate correlations (r = 0.14-0.39) between the EPDS and Mother-to-Infant Bonding Scale scores at each testing period. Women who experienced low mood tended to have stronger bonding disorder. Furthermore, the effectiveness of attachment between the mother and child was closely related to the mood of the mother as measured by the EPDS. CONCLUSION: We observed different patterns of bonding and maternal mood. Distinct subtypes regarding maternal mood and formation of mother-to-infant attachment suggests that analysis of bonding disorder should be performed considering the course of maternal depressive symptoms.