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Objective Volatile anesthetics are widely used for general anesthesia during surgical operations. Voltage-gated Na+ channels expressed in central neurons are major targets for volatile anesthetics; but it is unclear whether these drugs modulate native tetrodotoxin-resistant (TTX-R) Na+ channels, which are involved in the development and maintenance of inflammatory pain. Methods In this study, we examined the effects of sevoflurane on TTX-R Na+ currents (INa) in acutely isolated rat dorsal root ganglion neurons, using a whole-cell patch-clamp technique. Results Sevoflurane slightly potentiated the peak amplitude of transient TTX-R INa but more potently inhibited slow voltage-ramp-induced persistent INa in a concentration-dependent manner. Sevoflurane (0.86 ± 0.02 mM) (1) slightly shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) reduced the extent of use-dependent inhibition of Na+ channels, (3) accelerated the onset of inactivation and (4) delayed the recovery from inactivation of TTX-R Na+ channels. Thus, sevoflurane has diverse effects on TTX-R Na+ channels expressed in nociceptive neurons. Conclusions The present results suggest that the inhibition of persistent INa and the modulation of the voltage dependence and inactivation might be, at least in part, responsible for the analgesic effects elicited by sevoflurane.

With online learning solutions responding to the novel coronavirus pandemic, it is important for educational technologists and other practitioners to understand how learners are experiencing the demands of socially distanced online learning and how they conceive of themselves within distant spaces and digital communities. Research into the metacognitions of learners provides a non-technocratic focal point through which such information can be extracted. Framing learner self-beliefs as a form of metacognitive knowledge, the current article presents a virtual-reality-assisted thematic analysis into the self-appraisals of 210 socially distanced online learners at a Japanese university. The study focuses on the discursive rationalizations expressed in service of the academic self-concept. Four themes were identified in the data: formal assessment, affect and emotion, self-regulation, and transformative awareness. Such research provides educators with a platform for pedagogical intervention and course design considerations relative to the challenges of the online learning experience.

Purpose To clarify the incidence of and risk factors for febrile urinary tract infection in children with persistent vesicoureteral reflux (VUR) after the discontinuation of continuous antibiotic prophylaxis (CAP), retrospective chart review was performed. Patients and methods Among children with primary VUR at 10 years of age or younger at presentation, those who had persistent VUR despite conservative management with CAP and who were subsequently followed after discontinuation of CAP were included. Kaplan-Meier curve and Cox's proportional hazard regression model were used for evaluation of the incidence of and risk factors for febrile urinary tract infection (fUTI) after stopping CAP. Results Among 144 children (99 boys and 45 girls), fUTI developed in 34. The 5-year fUTI-free rate after discontinuation of CAP was 69.4%. On multivariate analyses, girls (p = 0.008) and abnormalities on nuclear renal scans (p = 0.0019), especially focal defect (p = 0.0471), were significant factors for fUTI. Although the fUTI-free rate was not different between children who had no or 1 risk factor, it was significantly lower in children with 2 risk factors than in those with no or 1 risk factor. Conclusions The present study revealed that girls and abnormal renal scan, especially focal defect, are risk factors for fUTI. Active surveillance without CAP for persistent VUR seems to be a safe option for children with no or 1 risk factor. Prophylactic surgery or careful conservative follow-up may be an option for girls with abnormal renal scan results if VUR persists under CAP.

Acquired idiopathic generalized anhidrosis is a rare disease with unknown etiology. Sudden loss of sweating function adversely affects young patients’ quality of life. Although systemic corticosteroid therapy is the most frequently reported treatment for the disease, its effectiveness is controversial because of the risk of recurrence. To assist clinical decision‐making regarding whether to use steroids, we investigated the treatment responsiveness and recurrence rates in patients undergoing steroid pulse therapy and explored factors affecting these rates. We retrospectively collected data of 124 patients who received steroid pulse therapy to calculate the rate of responsiveness to the therapy. We also conducted a time‐to‐event analysis in a cohort of 57 patients who responded to steroid pulse therapy to estimate the recurrence rate after the therapy. As a result, the response and recurrence rates were 73% and 48%, respectively. Recurrence occurred within 1 year in most patients. The overall effectiveness of steroid pulse therapy was estimated to be 57% considering the recurrence rate. A delay from onset to treatment and younger age appeared to be negative factors for effectiveness. Moreover, we found a significant seasonal effect on both treatment and recurrence: autumn was the worst season for acquired idiopathic generalized anhidrosis in Japan. Our study revealed that steroid pulse therapy can be expected to be effective in half of treated patients. We recommend starting the therapy promptly after the diagnosis; however, it is also worth considering the season for treatment planning.

Left polyorchidism was found in a 2-month-old boy with a left scrotal mass. As he was asymptomatic and all testes were in the scrotum, he was conservatively followed up. At 17 years of age, he presented with left acute scrotum due to testicular torsion of the left supernumerary testis. Counterclockwise 720-degree rotation of the left supernumerary testis was noted during emergency surgery, and orchidopexy of the 3 testes (2 left testes and 1 right testis) was performed. Biopsy of the left supernumerary testis demonstrated spermatogenesis and no malignancy. One and a half years after surgery, all testes were viable without atrophy.Polyorchidism is a rare condition and there is no consensus on the management of asymptomatic cases detected early in life. The position of the supernumerary testis (intrascrotal or extrascrotal) is important when deciding the management strategy because of the risk of malignancy. If conservative management is selected initially, elective surgery, such as prophylactic orchiectomy or orchidopexy, may be needed because of the risk of malignancy and torsion.

Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.

Background To investigate the need for ureteral reimplantation for vesicoureteral reflux (VUR) during augmentation cystoplasty (AC) in the long term. Methods A total of 19 patients with a median age at surgery of 14 years (3–38 years) who underwent AC for neurogenic bladder with VUR between 1983 and 2016 were included in this study. The changes in VUR grade and urodynamic findings were retrospectively evaluated. We evaluated the renal function by periodic inspection of serum creatinine level and estimated glomerular filtration rate; eGFR. Results The median follow-up period from AC was 14.8 years (5.7–30 years). VUR was detected in 19 patients, involving 27 ureters. Reflux grade was V in 6, IV in 9, III in 5, II in 6, and I in 1. Ureteral reimplantation was not performed in 18 patients (26 ureters), whereas it was done for 1 patient (1 ureter) in the early era of our experience. Postoperative videourodynamics showed that the reflux was radiologically not verifiable in 23 ureters (85%), was downgraded in 3 ureters (11%), and was unchanged in 1 ureter (3%). There were no cases of deterioration of VUR. Conclusions Ureteral reimplantation is not necessary for VUR during augmentation cystoplasty.

SummaryXeno-free culture systems have expanded the clinical and industrial application of human pluripotent stem cells (PSCs). However, yet some problems, such as the reproducibility among the experiments, remain. Here we describe an improved method for the subculture of human PSCs. The revised method significantly enhanced the viability of human PSCs by lowering DNA damage and apoptosis, resulting in more efficient and reproducible downstream applications such as gene editing, gene delivery, and directed differentiation. Furthermore, the method did not alter PSC characteristics after long-term culture and attenuated the growth advantage of abnormal subpopulations. This robust passaging method minimizes experimental error and reduces the rate of PSCs failing quality control of human PSC research and application.HighlightsThe revised passaging method significantly increases the viability of human PSCs.The method triggers less DNA damage and apoptosis signals compared to the conventional method.The stress-reduced method improves the results of downstream applications.The method does not alter PSC characters and attenuates the overgrowth of abnormal subpopulations.

Xeno-free culture systems have expanded the clinical and industrial application of human pluripotent stem cells (PSCs). However, reproducibility issues, often arising from variability during passaging steps, remain. Here, we describe an improved method for the subculture of human PSCs. The revised method significantly enhances the viability of human PSCs by lowering DNA damage and apoptosis, resulting in more efficient and reproducible downstream applications such as gene editing and directed differentiation. Furthermore, the method does not alter PSC characteristics after long-term culture and attenuates the growth advantage of abnormal subpopulations. This robust passaging method minimizes experimental error and reduces the rate of PSCs failing quality control of human PSC research and application.

The functional effect of a gene edit by designer nucleases depends on the DNA repair outcome at the targeted locus. While non-homologous end joining (NHEJ) repair results in various mutations, microhomology-mediated end joining (MMEJ) creates precise deletions based on the alignment of flanking microhomologies (µHs). Recently, the sequence context surrounding nuclease-induced double strand breaks (DSBs) has been shown to predict repair outcomes, for which µH plays an important role. Here, we survey naturally occurring human deletion variants and identify that 11 million or 57% are flanked by µHs, covering 88% of protein-coding genes. These biologically relevant mutations are candidates for precise creation in a template-free manner by MMEJ repair. Using CRISPR-Cas9 in human induced pluripotent stem cells (hiPSCs), we efficiently create pathogenic deletion mutations for demonstrable disease models with both gain- and loss-of-function phenotypes. We anticipate this dataset and gene editing strategy to enable functional genetic studies and drug screening., DNA repair by microhomology-mediated end joining creates precise deletions based on flanking microhomologies. Here the authors use CRISPR-Cas9 to recreate pathogenic deletion mutations using existing microhomologies in the human genome identified by their program MHcut.

Purpose The factors affecting spermatogenesis in adulthood in patients with hypospadias (HS) are not clearly understood. In the present study, risk factors affecting post-pubertal high serum follicle-stimulating hormone (FSH) were evaluated in patients with HS. Materials and methods Among those with a history of HS surgery, patients in whom endocrinological evaluation regarding pituitary–gonadal axis was performed at 15 years of age or older between March 2004 and April 2018 were enrolled in the present study. High serum FSH was defined as greater than 10 mIU/ml. The severity of HS was divided into mild and severe. Factors affecting the post-pubertal high serum FSH were estimated. Results Seventy-nine patients were included in the present study. The severity of HS was mild in 35 and severe in 44. History of undescended testis (UDT) was confirmed in 12. High serum FSH was detected in nine. On logistic regression model analysis, a history of UDT was the only significant factor for high serum FSH. The incidence of high serum FSH in patients with UDT was significantly higher than that in those without UDT (58.3% vs 7.5%, p

Human pluripotent stem cells (PSCs) express human endogenous retrovirus type-H (HERV-H), which exists as more than a thousand copies on the human genome and frequently produces chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and aberrant HERV-H expression attenuates neural differentiation potentials, however, little is known about the actual of function of HERV-H. In this study, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis of PSCs showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of the primed and naïve pluripotent states. The loss of ESRG hardly affected the global gene expression of PSCs or the differentiation potential toward trilineage. Differentiated cells derived from ESRG-deficient PSCs retained the potential to be reprogrammed into induced PSCs (iPSCs) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and recapturing of human pluripotency., Author summary We have been interested in the role of human endogenous retrovirus (HERVs) in human pluripotent stem cells (PSCs). Although we and others have demonstrated that HERV expression is crucial for somatic cell reprogramming to a pluripotent state and the characteristics of PSCs. Little is known which one of more than 1,000 copies of HERVs is important. Thus, in this study, we focused on a HERV-related gene, ESRG which is expressed strongly and specifically in human PSCs but not in differentiated cells. Using a CRISPR/Cas9 platform, we generated complete knockout cell lines by deleting the entire gene body of ESRG. Our results demonstrate that ESRG is dispensable for the PSC characters such as gene expression, self-renewing capacity, and differentiation potential. In addition, ESRG does not contribute to the reprogramming of differentiated cells to a pluripotent state. Altogether, we concluded that ESRG is an excellent marker of pluripotency but dispensable for the PSC identity.

Propranolol, a representative adrenergic β-receptor antagonist, is widely used to prevent migraine attacks. Although propranolol is well known to inhibit tetrodotoxin-resistant (TTX-R) Na

Sevoflurane, which is preferentially used as a day-case anesthetic based on its low blood solubility, acts on the central nervous system and exerts analgesic effects. However, it still remains unknown whether sevoflurane affects the excitability of nociceptive sensory neurons. Therefore, we conducted this study to examine the effects of sevoflurane on the excitability of small-sized dorsal root ganglion (DRG) neurons of rats using the whole-cell patch-clamp technique. In a voltage-clamp condition, sevoflurane elicited the membrane current in a concentration-dependent manner, in which the reversal potential was similar to the equilibrium potential of K

Human pluripotent stem cells (PSCs) express human endogenous retrovirus type-H (HERV-H), which exists as more than a thousand copies on the human genome and frequently produces chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and aberrant HERV-H expression attenuates neural differentiation potentials, however, little is known about the actual of function of HERV-H. In this study, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis of PSCs showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of the primed and naïve pluripotent states. The loss of ESRG hardly affected the global gene expression of PSCs or the differentiation potential toward trilineage. Differentiated cells derived from ESRG-deficient PSCs retained the potential to be reprogrammed into induced PSCs (iPSCs) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and recapturing of human pluripotency.

Sacrococcygeal teratoma (SCT) is the most common fetal and neonatal tumor. While SCT is often associated with urological problems, the association between SCT and a urogenital sinus (UGS) anomaly is rare. A concurrent UGS anomaly may be an acquired condition due to resection of SCT because it is rarely found at birth. In our case in whom fetal imaging study showed an abdominal cystic lesion, SCT with a UGS anomaly was suspected at birth and confirmed by endoscopy before resection of SCT during the neonatal period. These findings revealed that UGS anomaly may develop congenitally.

We investigated the effects of nitrous oxide (N2O) on glycinergic inhibitory whole-cell and synaptic responses using a "synapse bouton preparation," dissociated mechanically from rat spinal sacral dorsal commissural nucleus (SDCN) neurons. This technique can evaluate pure single- or multi-synaptic responses from native functional nerve endings and enable us to accurately quantify how N2O influences pre- and postsynaptic transmission. We found that 70 % N2O enhanced exogenous glycine-induced whole-cell currents (IGly) at glycine concentrations lower than 3 × 10-5 M, but did not affect IGly at glycine concentrations higher than 10-4 M. N2O did not affect the amplitude and 1/e decay-time of both spontaneous and miniature glycinergic inhibitory postsynaptic currents recorded in the absence and presence of tetrodotoxin (sIPSCs and mIPSCs, respectively). The decrease in frequency induced by N2O was observed in sIPSCs but not in mIPSCs, which was recorded in the presence of both tetrodotoxin and Cd2+, which block voltage-gated Na+ and Ca2+ channels, respectively. N2O also decreased the amplitude and increased the failure rate and paired-pulse ratio of action potential-evoked glycinergic inhibitory postsynaptic currents. N2O slightly decreased the Ba2+ currents mediated by voltage-gated Ca2+ channels in SDCN neurons. We found that N2O suppresses glycinergic responses at synaptic levels with presynaptic effect having much more predominant role. The difference between glycinergic whole-cell and synaptic responses suggests that extrasynaptic responses seriously modulate whole-cell currents. Our results strongly suggest that these responses may thus in part explain analgesic effects of N2O via marked glutamatergic inhibition by glycinergic responses in the spinal cord.

Objectives To identify the types of serotonin (5-hydroxytryptamine) receptors of the prefrontal cortex related to the micturition reflex. Methods Female Sprague-Dawley rats and a microinjection method were used for this study. Stainless steel guide cannulas were implanted bilaterally into the prefrontal cortex, and a polyethylene catheter was inserted into the bladder. Cystometric parameters (intercontraction interval and maximum voiding pressure) were measured before and after injection of any one of six specific antagonists of 5-hydroxytriptamine receptors (5-hydroxytryptamine 1A, 5-hydroxytryptamine 2A, 5-hydroxytryptamine 2C, 5-hydroxytryptamine 3, 5-hydroxytryptamine 4 and 5-hydroxytryptamine 7) into the prefrontal cortex. The prefrontal cortex was divided into two regions, namely the prelimbic cortex and the infralimbic cortex. The experiments were carried out in conscious and free-moving rats. Results The intercontraction interval value increased significantly after injection of the 5-hydroxytriptamine 2A receptor antagonist, MDL11939, into the prelimbic cortex of the rat prefrontal cortex (7.68 +/- 1.28vs9.02 +/- 1.41 min,P < 0.05), whereas the intercontraction interval value decreased significantly after injection of the 5-hydroxytriptamine 7 antagonist SB269970 into the prelimbic cortex (9.42 +/- 0.39vs8.14 +/- 0.71 min,P < 0.05). The intercontraction interval was unaffected by injection of either of these two antagonists into the infralimbic cortex. The other four antagonists (5-hydroxytryptamine 1A, 5-hydroxytryptamine 2C, 5-hydroxytryptamine 3 and 5-hydroxytryptamine 4) had no effect on the intercontraction interval after injection into the prelimbic cortex and the infralimbic cortex. The maximum voiding pressure was unaffected by injection of any one of the six 5-hydroxytriptamine antagonists into the prelimbic cortex and infralimbic cortex. Conclusions In the rat prefrontal cortex5-hydroxytryptamine 2A receptors excite the micturition reflex, whereas 5-hydroxytryptamine 7 receptors inhibit this reflex.

ASPEN(American Society for Parenteral and Enteral Nutrition)は1976年に米国で設立され、臨床栄養・代謝の研究と実践を通して患者のケアを改善することを目指している。世界中に会員がおり、2017年現在6,500名以上で構成され、メンバーは医師、管理栄養士、薬剤師、看護師、研究者、学生などである。会員は、栄養サポートに関する臨床実践、研究、教育の向上を追究している。ASPEN2017年は、2月18日～21日に米国のOrlando World Center Marriott Resort and Convention Center in Orlandoで開催され、メインテーマはClinical Nutrition Week(CNW : 臨床栄養研究)であった。発表テーマや内容は臨床における患者の栄養管理の基礎研究・実践研究に関する大変興味深いものであった。以下、筆者らが発表した「クローン病患者のn-3 系多価不飽和脂肪酸摂取と血清脂肪酸の特徴-潰瘍性大腸炎患者との比較-」を紹介する。

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Objectives To investigate the impact of preoperative ultrasonography (US) for detecting a viable testis in patients with a unilateral nonpalpable testis. Methods Patients with a unilateral nonpalpable testis or unilateral palpable undescended testis who underwent preoperative US were enrolled. Patients were divided into 3 groups as follows: nonpalpable testis/no testis (n = 27), which included patients who had a unilateral nonpalpable testis with no viable testis detected at surgery; nonpalpable testis/viable testis (n = 10), which included patients who had a unilateral nonpalpable testis with a viable testis identified at surgery; and palpable undescended testis (n = 63), which included patients who had a unilateral palpable undescended testis. Preoperative US findings were compared among each group. Results The testicular volume on the contralateral descended side in the nonpalpable testis/no testis group was significantly greater than that in the nonpalpable testis/viable testis and palpable undescended testis groups. When a testicular volume of 0.54 mL was used as the cutoff value, the sensitivity, specificity, positive predictive value, and negative predictive value for the presence of the affected testis were 75.3%, 100%, 100%, and 60.0%, respectively. The testis on the affected side was detected in none of the nonpalpable testis/no testis group, 7 of the nonpalpable testis/viable testis group, and all of the palpable undescended testis group. When a visible testis on the affected side and a testicular volume of 0.54 mL or less were defined as positive, all patients in the nonpalpable testis/viable testis and palpable undescended testis groups had positive findings versus none in the nonpalpable testis/no testis group. Conclusions Preoperative US provides valuable information for predicting the presence of a viable testis in patients with a unilateral nonpalpable testis by estimating both the unaffected testis and the affected side.

Sevoflurane, which is preferentially used as a day-case anesthetic based on its low blood solubility, acts on the central nervous system and exerts analgesic effects. However, it still remains unknown whether sevoflurane affects the excitability of nociceptive sensory neurons. Therefore, we conducted this study to examine the effects of sevoflurane on the excitability of small-sized dorsal root ganglion (DRG) neurons of rats using the whole-cell patch-clamp technique. In a voltage-clamp condition, sevoflurane elicited the membrane current in a concentration-dependent manner, in which the reversal potential was similar to the equilibrium potential of K+. In a current-clamp condition, sevoflurane directly depolarized the membrane potentials in a concentration-dependent manner. Moreover, at a clinically relevant concentration, sevoflurane decreased the threshold for action potential generation. These findings suggest that sevoflurane acts on the leak K+ channels to increase the excitability of DRG neurons. Sevoflurane increased the half-width of single action potentials, which resulted from the inhibition of voltage-gated K+ currents, including the fast inactivating A-type and non-inactivating delayed rectifier K+ currents. Our study indicates that sevoflurane could exhibit pronociceptive effects on nociceptive sensory neurons by inhibiting K+ conductances.

Objective To clarify the prevalence and chronological changes of testicular microlithiasis in isolated congenital undescended testes, retrospective chart review was performed. Materials and Methods Among children with palpable isolated undescended testes who underwent orchiopexy at less than 3 years of age between January 2009 and May 2016, those who had preoperative testicular ultrasonography were enrolled. Testicular microlithiasis was classified as limited or classic. Results Sixty-five patients (54 unilateral undescended testes and 11 bilateral undescended testes) were enrolled. Preoperative evaluation demonstrated limited testicular microlithiasis in only 2 undescended testes in 2 patients (1 with unilateral undescended testes and 1 with bilateral undescended testes). Of these patients, 1 with unilateral undescended testes had limited testicular microlithiasis and the other with bilateral undescended testes had classic testicular microlithiasis after surgery. Among 53 unilateral undescended testes without microlithiasis preoperatively, limited and classic testicular microlithiasis was found in 1 and 6 testes, respectively, during follow-up. Testicular microlithiasis was identified in 2 on the contralateral descended testis of unilateral undescended testes postoperatively. Among 10 patients with bilateral undescended testes without microlithiasis preoperatively, limited testicular microlithiasis was detected in 4 during follow-up. Testicular microlithiasis was not diminished or resolved during follow-up. The overall prevalence of testicular microlithiasis in undescended testes (21.1%) was significantly higher than that in the contralateral descended testis in patients with unilateral undescended testes (3.7%) (P Conclusion Most testicular microlithiasis was identified postoperatively and never improved. The prevalence of testicular microlithiasis in isolated congenital undescended testes increased with time even if operated on early in life.

Background Ureterocalicostomy is indicated mainly in cases with failed pyeloplasty or with a completely intrarenal pelvis. While there have been several case series reported in adults, laparoscopic ureterocalicostomy in pediatric cases has rarely been reported. We report a case of pure laparoscopic ureterocalicostomy for ureteropelvic junction obstruction in an Asian female child. Case presentation A 10-year-old female patient was referred to our hospital due to right high-grade hydronephrosis and a right renal stone, which was detected due to hematuria. Laparoscopic pyelolithotomy and ureterocalicostomy were indicated because of the completely intrarenal pelvis with thinning of the cortex, especially at the lower calyx. A transperitoneal approach was implemented in a lateral flank position with four trocars. After exposing the renal hilum, the renal stone was extracted without lithotripsy by making a small longitudinal incision at the ureteropelvic junction. Then, the ureter was transected, and the renal pelvis was closed. A 2-cm incision was made at the lower calyx. Uretero-caliceal anastomosis was completed in a running fashion using 5-0 absorbable sutures. The operation time was 379 min. The postoperative course was uneventful. Postoperative imaging studies showed marked improvement of the right hydronephrosis. Conclusion Laparoscopic ureterocalicostomy is a safe and feasible treatment for selected patients with complicated ureteropelvic junction obstruction, even in the pediatric population.

We recently reported that adeno-associated virus serotype 1-constitutively active Ras homolog enriched in brain [AAV1-Rheb(S16H)] transduction of hippocampal neurons could induce neuron-astroglia interactions in the rat hippocampus in vivo, resulting in neuroprotection. However, it remains uncertain whether AAV1-Rheb(S16H) transduction induces neurotrophic effects and preserves the cognitive memory in an animal model of Alzheimer&rsquo, s disease (AD) with characteristic phenotypic features, such as &beta, amyloid (A&beta, ) accumulation and cognitive impairments. To assess the therapeutic potential of Rheb(S16H) in AD, we have examined the beneficial effects of AAV1-Rheb(S16H) administration in the 5XFAD mouse model. Rheb(S16H) transduction of hippocampal neurons in the 5XFAD mice increased the levels of neurotrophic signaling molecules, including brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), and their corresponding receptors, tropomyosin receptor kinase B (TrkB) and CNTF receptor &alpha, subunit (CNTFR&alpha, ), respectively. In addition, Rheb(S16H) transduction inhibited A&beta, production and accumulation in the hippocampus of 5XFAD mice and protected the decline of long-term potentiation (LTP), resulting in the prevention of cognitive impairments, which was demonstrated using novel object recognition testing. These results indicate that Rheb(S16H) transduction of hippocampal neurons may have therapeutic potential in AD by inhibiting A&beta, accumulation and preserving LTP associated with cognitive memory.

"Comfort set for palliative care"is narrowly defined as a set of drugs used to alleviate symptoms at the terminal stage. However, we think that the followingis important(1)The practice of advance care planning(ACP)is indispensable and it is done accordingto the situation after the start of the visit, but our clinic emphasizes careful consultation before the start as a means of team formation with the patient's family and the doctor.(2)Introduction of visitingmedicine management by pharmacist of dispensingpharmacy is preferable for the method of supply/inventory of drugs. 98% of cancer patients in our clinic use it. In addition, we have injection drugs, devices and emergency drugs in the clinic so that we can respond quickly.(3) Seamless collaboration with visitingnursingis necessary for understandingand implementingthe situation that medicines should be used. All cancer patients in our clinic are receivingvisitingnursingby in-clinic nurses. We mentioned the point that seems to be important points in past practice for "comfort of patient, family member and medical staff" in home palliative care.