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Background: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. Methods: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. Results: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups. Conclusion: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT). Methods: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (β-blocker) (Cohort 2); PG analogue, β-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout. Results: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of − 2.7 to − 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity. Conclusion: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT. Trial registration: Japan Registry of Clinical Trials Identifier: jRCT2080225063. Date of registration: 17 February 2020. [ABSTRACT FROM AUTHOR]

Whether in ant–aphid mutualism the ants exert evolutionary selection pressure on aphid morphology has not yet been fully tested. Here, we tested whether the long proboscises of Stomaphis yanonis (Aphididae Lachninae) aphids confer an advantage in preventing predation by the tending ants. Specifically, we tested the hypothesis that aphids with a shorter proboscis would excrete less honeydew, making them more likely to be preyed upon by ants. Our results showed that aphid individuals with a shorter proboscis took up less phloem sap and excreted less honeydew than individuals with a longer proboscis. In addition, among aphids with a similar body size, those with a shorter proboscis were more susceptible to predation by ants than those with a longer proboscis. These results suggest that predation by tending ants, by exerting selection pressure on aphid proboscis morphology, has caused the aphids to evolve longer proboscises. [ABSTRACT FROM AUTHOR]

Background: Murray law-based quantitative flow ratio (μQFR) is a novel computational method that enables accurate estimation of fractional flow reserve (FFR) using a single angiographic projection. However, its diagnostic value in patients with severe aortic stenosis (AS) remains unclear. Method: We included 25 consecutive patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS with intermediate or greater (30–90%) coronary artery disease (CAD). Pre- and post-TAVR μQFR, QFR, instantaneous flow reserve (iFR), and post-TAVR invasive FFR values were measured. We evaluated the diagnostic performance of pre-TAVR μQFR, QFR, and iFR using post-TAVR FFR ≤ 0.80 as a reference standard of ischemia. Result: Pre-TAVR μQFR was significantly correlated with post-TAVR FFR (r = 0.73, p < 0.0001). The area under the curve of pre-TAVR μQFR on post-TAVR FFR ≤ 0.8 was 0.91 (95% confidence interval [CI] 0.77–0.98), comparable to that of pre-TAVR iFR (0.86 [95% CI 0.71–0.98], p = 0.97). The accuracy, sensitivity, specificity, and positive and negative predictive values of pre-TAVR μQFR on post-TAVR FFR ≤ 0.8 were 84.2% (95% CI 68.7–93.4), 61.6% (95% CI 31.6–86.1), 96.0% (95% CI 79.6–99.9), 88.9% (95% CI 52.9–98.3), and 82.8% (95% CI 70.6–90.6), respectively. For pre-TAVR iFR, these values were 76.5% (95% CI 58.8–89.3), 90.9% (95% CI 58.7–99.8), 69.6% (95% CI 47.1–86.8), 58.8% (95% CI 42.8–73.1), and 94.1% (95% CI 70.8–99.1), respectively. Conclusion: μQFR could be useful for the physiological evaluation of patients with severe AS with concomitant CAD. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. Methods: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways. [ABSTRACT FROM AUTHOR]

To examine changes in individuals' psychosocial variables (e.g., psychological distress, social isolation, and alcohol use) during the prolonged COVID-19 pandemic, a two-year longitudinal survey was conducted at approximately one-year intervals between May 2020 and May 2022, after the first COVID-19-related state of emergency was announced in Japan. The online survey was conducted on May 11-12, 2020 (Phase 1), June 14–20, 2021 (Phase 2), and May 13–30, 2022 (Phase 3). The survey in Phase 1 was conducted during the first emergency declaration period, the survey in Phase 2 was conducted during the third emergency declaration period, and the survey in Phase 3 was conducted at a time when there was no state of emergency but many COVID-19 positive cases. Notably, 3,892 participants responded to all three surveys. In addition to psychosocial inventories often used worldwide, survey items included lifestyle and stress management indicators related to COVID-19 and various sociodemographic items including occupation (e.g., healthcare workers) or income, history of medical treatment for mental problems, severe physical illnesses, and COVID-19. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that an extremely strong desire for happiness might ironically reduce a person's well-being, particularly among Western people. According to the goal progress theory and the theory of valuing happiness, rumination might explain the relationship between valuing happiness and well-being. Based on these theoretical rationales, this study examined the following hypotheses: (1) valuing happiness is significantly associated with rumination, (2) people who experience low life stress have a stronger association between valuing happiness and rumination, and (3) people with more interdependent self-construal have a weaker association between valuing happiness and rumination. University students in Japan participated in a cross-sectional study (N = 350; Study 1) and a 4-weeks longitudinal study (N = 329; Study 2). They responded to a packet of questionnaires assessing valuing happiness, trait rumination, depressive symptoms, negative events, and interdependent self-construal. Consistent with our hypothesis, valuing happiness was concurrently and longitudinally associated with increased rumination after controlling for depressive symptoms. However, negative events did not moderate the association between valuing happiness and rumination. Furthermore, Study 1, but not Study 2, indicated that the association between valuing happiness and rumination was stronger among students with highly interdependent self-construal than those with less interdependent self-construal. The preset findings indicated that valuing happiness might be a factor that perpetuates rumination. More sophisticated evidence on the influence of valuing happiness on rumination can lead to effective psychotherapies for decreasing rumination and depression. [ABSTRACT FROM AUTHOR]

Interoception, which pertains to the physiological state of the body, is associated with subjective emotional experiences. In particular, the accuracy of perceiving interoceptive signals (interoceptive accuracy [IAcc]) is linked to the intensity of emotional arousal, known as arousal focus (AF). IAcc is believed to influence the granularity of emotional experiences. Here, we examined the relationship between IAcc and assessment and verbalisation of one's own or others' emotions. Study I demonstrated that individuals with higher IAcc exhibited significantly greater AF when evaluating their own positive emotions. Furthermore, although no correlation between IAcc and AF was found in free descriptions of emotions, a significant positive correlation was found between IAcc and the number of emotion-related words. Study II showed that individuals with higher IAcc displayed significantly higher AF when assessing the positive emotions of characters in videos. Additionally, in free descriptions of these characters, a significant positive correlation was observed between predicted verbal IQ and the number of emotion-related words. These findings support the notion that interoception is associated with AF during assessment of one's own or others' positive emotions as well as the abundance of emotion-related words. This study demonstrates the relationship between bodily sensations and social aspects of human embodiment. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) has been thought to be the biophysical principle governing the assembly of the multiphase structures of nucleoli, the site of ribosomal biogenesis. Condensates assembled through LLPS increase their sizes to minimize the surface energy as far as their components are available. However, multiple microphases, fibrillar centers (FCs), dispersed in a nucleolus are stable and their sizes do not grow unless the transcription of pre-ribosomal RNA (pre-rRNA) is inhibited. To understand the mechanism of the suppression of the FC growth, we here construct a minimal theoretical model by taking into account nascent pre-rRNAs tethered to FC surfaces by RNA polymerase I. The prediction of this theory was supported by our experiments that quantitatively measure the dependence of the size of FCs on the transcription level. This work sheds light on the role of nascent RNAs in controlling the size of nuclear bodies. Theoretical modeling and experimental tests shed light on the roles of nascent prerRNA, produced by Pol I transcription, in the assembly of the sea-island multi-phase structure in the nucleolus. [ABSTRACT FROM AUTHOR]

Purpose: Bony morphology has been proposed as a potential risk factor for anterior cruciate ligament (ACL) injury. The relationship between bony morphology, knee kinematics, and ACL elongation during high-demand activities remains unclear. The purpose of this study was to determine if bone morphology features that have been associated with ACL injury risk and knee kinematics are also predictive of ACL elongation during fast running and double-legged drop jump. Methods: Nineteen healthy athletes performed fast running and double-legged drop jump within a biplane radiography imaging system. Knee kinematics and ACL elongation were measured bilaterally after using a validated registration process to track bone motion in the radiographs and after identifying ACL attachment sites on magnetic resonance imaging (MRI). Bony morphological features of lateral posterior tibial slope (LPTS), medial tibial plateau (MTP) depth, and lateral femoral condyle anteroposterior width (LCAP)/lateral tibial plateau anteroposterior width (TPAP) were measured on MRI. Relationships between bony morphology and knee kinematics or ACL elongation were identified using multiple linear regression analysis. Results: No associations between bony morphology and knee kinematics or ACL elongation were observed during fast running. During double-legged drop jump, a greater range of tibiofemoral rotation was associated with a steeper LPTS (β = 0.382, p = 0.012) and a deeper MTP depth (β = 0.331, p = 0.028), and a greater range of anterior tibial translation was associated with a shallower MTP depth (β = − 0.352, p = 0.018) and a larger LCAP/ TPAP (β = 0.441, p = 0.005); however, greater ACL elongation was only associated with a deeper MTP depth (β = 0.456, p = 0.006) at toe-off. Conclusion: These findings indicate that observed relationships between bony morphology and kinematics should not be extrapolated to imply a relationship also exists between those bone morphology features and ACL elongation during high-demand activities. These new findings deepen our understanding of the relationship between bony morphology and ACL elongation during high-demand activities. This knowledge can help identify high-risk patients for whom additional procedures during ACL reconstruction are most appropriate. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA). Methods: This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated. Results: The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P =.007). Conclusion: In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery. [ABSTRACT FROM AUTHOR]

Oral microbiome studies have mainly focussed on bacteria, with the relationship between viruses and oral cancers remaining poorly understood. Oral cancers can develop even in the absence of any history of daily smoking or drinking. Oral cancer patients frequently have multiple primary cancers in the oral cavity and other organs, such as the upper gastrointestinal tract. Merkel cell polyomavirus (MCPyV) is a novel oncovirus identified from a subtype of skin cancer in 2008. In this study, we investigated the potential involvement of MCPyV in the pathogenesis of oral squamous cell carcinoma (OSCC). Participants comprised 115 Japanese patients with OSCC (single primary: 109 tumours in 109 patients; multiple primaries: 16 tumours in 6 patients) treated in our department between 2014 and 2017. DNA was extracted from formalin-fixed paraffin-embedded specimens of primary lesions. MCPyV DNA copy counts were analysed by quantitative real-time polymerase chain reaction. Twenty-four of the 115 patients (20.9%) were positive for MCPyV DNA. No association was found between presence or absence of MCPyV DNA and clinical characteristics other than number of primary lesions. The MCPyV DNA-positive rate was significantly higher for multiple primary OSCCs (62.5%, 10/16 tumours) than for single primary OSCCs (16.5%, 18/109 tumours; P < 0.001). Furthermore, MCPyV DNA load was significantly higher for patients with multiple primaries (P < 0.05). MCPyV was observed more frequently and DNA load was significantly higher with multiple primary OSCCs than with single primary OSCC. MCPyV may play some role as an oncovirus for multiple primary OSCCs. [ABSTRACT FROM AUTHOR]

Background: In the past, different stress generation studies have used self-report measures comprising different items to assess each category of negative events. Moreover, the validity of these scales has not been adequately investigated. Therefore, we developed a self-report measure dedicated to assessing experiences of negative interpersonal dependent events, negative non-interpersonal dependent events, and negative independent events in university students, which was named the Negative Independent/Dependent Events Scale. Methods: Japanese undergraduate students (N = 247; mean age = 19.18 years, SD = 3.08) responded to the Negative Independent/Dependent Events Scale, which had items selected for adequate content validity. They also responded to self-report measures of depressive symptoms, reassurance-seeking behaviors, inattention, and lack of perseverance. Results: All the negative events subscales had moderate positive correlations with depressive symptoms. In addition, the negative interpersonal dependent events subscale showed a moderate positive correlation with reassurance-seeking behaviors, and the negative non-interpersonal dependent events subscale showed a strong positive correlation with inattention. Furthermore, the negative non-interpersonal dependent events subscale was more strongly correlated with inattention than the other two negative events subscales. In contrast, the negative interpersonal dependent events subscale was more strongly correlated with reassurance-seeking behaviors than with the negative independent events subscale but not more strongly than with the negative non-interpersonal dependent events subscale. Conclusions: These findings indicated the acceptable construct validity of the Negative Independent/Dependent Events Scale. However, further research is necessary to establish the discriminant validity of the negative interpersonal dependent events subscale and the negative non-interpersonal dependent events subscale. [ABSTRACT FROM AUTHOR]

Motivated by our recent experiments that demonstrate that the tandemly repeated genes become heterochromatin, here we show a theory of heterochromatin assembly by taking into account the connectivity of these genes along the chromatin in the kinetic equations of small RNA production and histone methylation, which are the key biochemical reactions involved in the heterochromatin assembly. Our theory predicts that the polymeric nature of the tandemly repeated genes ensures the steady production of small RNAs because of the stable binding of nascent RNAs produced from the genes to RDRC/Dicers at the surface of nuclear membrane. This theory also predicts that the compaction of the tandemly repeated genes suppresses the production of small RNAs, consistent with our recent experiments. This theory can be extended to the small RNA-dependent gene silencing in higher organisms. A kinetic model evaluates the relationship between heterochromatin assembly, small RNA production, and histone methylation in fission yeast. [ABSTRACT FROM AUTHOR]

Introduction: Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil–brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α2-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components—ripasudil or brimonidine. Methods: This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics. Results: Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC. Conclusion: RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC. Trial Registration: Japan Registry of Clinical Trials; Registration No. jRCT2080225220. [ABSTRACT FROM AUTHOR]

Pre-ribosomal RNAs are synthesized during the transcription by RNA polymerase I molecules localized at the surfaces of a nucleolus subcompartment. Inspired by the ribosomal RNA transcription, we here develop a scaling theory of a brush of polymers, where monomers are added to their grafted ends in the steady state. Our theory predicts that monomers newly added to the polymers stay at the vicinity of the surface due to the slow dynamics of the polymers and thus the polymer volume fraction increases with increasing the polymerization rate. The excluded volume interaction between polymers and reactant monomers suppresses the diffusion of reactant monomers and thus decreases the polymerization rate. The extent of the suppression of monomer diffusion increases with increasing the polymerization rate because the diffusion length decreases, rather than the condensation of polymers due to their slow dynamics. [ABSTRACT FROM AUTHOR]

This study determined the predictive accuracy of optical frequency domain imaging (OFDI) on debulking effects of rotational atherectomy (RA) and compared the predictive accuracy of OFDI catheter-based with Rota wire-based prediction methods. This prospective, single-center, observational study included 55 consecutive patients who underwent OFDI-guided RA. On pre-RA OFDI images, a circle, identical to the Rota burr was drawn at the center of the OFDI catheter (OFDI catheter-based prediction method) or wire (wire-based prediction method). The area overlapping the vessel wall was defined as the predicted ablation area (P-area). The actual ablated area (A-area) was measured by superimposing the OFDI images before and after RA. The overlapping P-area and A-area were defined as overlapped ablation area (O-area), and the predictive accuracy was evaluated by %Correct area (O-area/P-area) and %Error area (A-area − O-area/A-area). The median %Correct and %Error areas were 47.8% and 41.6%, respectively. Irrelevant ablation (low %Correct-/high % Error areas) and over ablation (high %Correct-/high % Error areas) were related to deep vessel injury and intimal flap outside the P-area. The predictive accuracy was better in the OFDI catheter-based prediction method than the wire-based prediction method in the cross sections where the OFDI catheter and wire came in contact. However, it was better in the latter than the former where the OFDI catheter and wire were not in contact. OFDI-based simulation of the RA effect is feasible though accuracy may be affected by the OFDI catheter and wire position. OFDI-based simulation of RA effect might reduce peri-procedural complications during RA. [ABSTRACT FROM AUTHOR]

The present study examined the causes and consequences of stress generation in university students in Japan. A two-wave longitudinal study with an 8- or 9-week interval was conducted in the fall of 2020. Undergraduate and graduate students at four universities in Japan (N = 201) completed self-report measures assessing experiences of negative interpersonal dependent events, negative non-interpersonal events, and negative independent events at two times. At the same time, they also responded to measures of aggressive behaviors, trait rumination, and depressive symptoms. Path analyses revealed that baseline aggressive behaviors were positively associated with an increase in subsequent negative interpersonal dependent events, even after controlling for the influences of negative interpersonal dependent events, rumination, and depressive symptoms at baseline. However, aggressive behaviors were not significantly associated with subsequent negative non-interpersonal dependent events or negative independent events. These findings suggest that aggressive behaviors may have been a factor leading to interpersonal stress generation. Furthermore, all categories of negative event experiences predicted an increase in subsequent depressive symptoms, but not subsequent rumination, and rumination was not significantly associated with subsequent depressive symptoms. This research extends previous studies on the causes and consequences of stress generation conducted in the US by using specific measures of aggressive behaviors and including a non-restricted sample of university students in Japan. [ABSTRACT FROM AUTHOR]

It is known that a nevoid basal cell carcinoma syndrome (NBCCS) is characterized by a combination of developmental abnormalities and a predisposition to form various tumors. Although it is possible to create disease models via gene editing, there are significant potential problems with this approach such as off-target mutations and differences in SNPs. On the other hand, since disease families share common SNPs, research using iPSCs derived from both patients and healthy siblings of the same disease family is very important. Thus, establishment of induced pluripotent stem cells derived from patients and healthy siblings of the same NBCCS family will be of great importance to study the etiology of this disease and to develop therapeutics. In this study, we generated hiPSCs using peripheral blood mononuclear cells derived from the patients and healthy siblings of familial NBCCS with the novel mutation in PTCH1_c.3298_3299insAAG in the feeder- and serum-free culture conditions using SeVdp. In addition, disease-specific hiPSCs such as those expressing the PTCH1_c.3298_3299insAAG mutation could be powerful tools for revealing the genotype-phenotype relationship and pathogenicity of NBCCS. [ABSTRACT FROM AUTHOR]

In angiosperms, intraspecific variation of flowering phenology may affect reproductive isolation and, consequently, speciation. This study focused on Impatiens noli-tangere (Balsaminaceae), which is distributed over broad latitudinal and altitudinal ranges in Japan. We aimed to reveal the phenotypic mixture of two ecotypes of I. noli-tangere with different flowering phenology and morphological traits in a narrow contact zone. Previous studies have shown that I. noli-tangere has early- and late-flowering types. The early-flowering type makes buds in June and is distributed at high-elevation sites. The late-flowering type makes buds in July and is distributed at low-elevation sites. In this study, we analyzed the flowering phenology of individuals at an intermediate elevation site where the early- and late-flowering types grow in sympatry (contact zone). We found no individuals showing intermediate flowering phenology at the contact zone, and early- and late-flowering types were clearly distinguishable. We also found that the differences in many other phenotypic traits between the early- and late-flowering types were maintained, including the number of flowers produced (total number of chasmogamous and cleistogamous flowers), leaf morphology (aspect ratio, number of serrations), seed traits (aspect ratio), and flower bud formation positions on the plant. This study showed that these two flowering ecotypes maintain many different traits in sympatry. [ABSTRACT FROM AUTHOR]

Background: Optimal hemostasis provides safety and reliability during neurosurgery which improves surgical outcomes. Previously, artificial cerebrospinal fluid (aCSF) and its component sodium bicarbonate were found to facilitate physiological hemostasis by amplifying platelet aggregation. This study aimed to verify whether aCSF amplifies platelet-dependent hemostasis in the presence of antiplatelet agents. Methods: We prepared platelet-rich plasma (PRP) or washed platelets using aspirin (acetylsalicylic acid, (ASA)) or normal saline (NS). We evaluated samples treated with a commercially available aCSF solution or NS for amplification of aggregation, activation of integrin αIIbβ3, phosphatidylserine (PS) exposure, P-selectin (CD62P) expression, and formation of microparticles (MPs). We assessed the effect of aCSF on in vivo hemostasis in the presence of ASA by measuring the tail bleeding time in ASA-or NS-injected C57BL/6 N mice. Results: Compared with NS, aCSF amplified ASA-inhibited platelet aggregation by recovering platelet activation including PS exposure, MP release, CD62P expression, and integrin αIIbβ3 activation. When using washed platelets, aCSF almost completely counteracted the inhibition of platelet aggregation by ASA. Prolonged bleeding time from the amputated tail of ASA-injected mice was significantly shortened by the treatment with aCSF compared to NS. Sodium bicarbonate also directly amplified ASA-inhibited platelet aggregation. Conclusions: aCSF and sodium bicarbonate facilitate physiological hemostasis through the recovery of inhibited platelet aggregation even in the presence of ASA. The utilization of aCSF in the operative field may be advantageous for facilitating hemostasis in patients with impaired platelet function and contribute to improving outcomes of neurosurgery. [ABSTRACT FROM AUTHOR]

Purpose: Observation is the first management option in asymptomatic meningiomas, but when an enlargement or mass effect is observed, surgery is indicated. This study is aimed at exploring risk factors for complications and recurrence after surgery for asymptomatic meningioma. We also examined the impact of preoperative tumor embolization, which is considered controversial. Methods: We retrospectively reviewed 109 patients with primary asymptomatic meningiomas surgically treated at our institute between April 2007 and March 2021. Patients who only had headaches as a nonspecific complaint were included in the asymptomatic group. Complications, time to recurrence, and Glasgow Outcome Scale (GOS) score were the endpoints of the study. Risk factors for complications and recurrence were explored. Moreover, the effect of the resection on nonspecific headaches was also explored. Results: The permanent postoperative complication rate related to the surgical procedure was 1.8%. Of the total, 107 patients (98.2%) with asymptomatic meningiomas who were surgically treated achieved a GOS score of 5 1 year after the operation. Preoperative headache was present in 31 patients and improved postoperatively in 21 patients. Multivariate analysis using the Cox proportional hazard model showed that preoperative tumor embolization with > 80% resolution of tumor staining (p < 0.001) was negatively related to recurrence, whereas age (p = 0.046) and Simpson grade IV resection (p = 0.041) were positively related to recurrence. Conclusion: Although surgery for asymptomatic meningiomas can, in many cases, be safe, it is not free of complications Thus, surgical intervention for asymptomatic meningiomas should be considered cautiously. However, more than half the patients with headaches showed improvement. Simpson grade IV resection cases should be assessed for recurrence, and preoperative tumor embolization might be effective in controlling recurrence. [ABSTRACT FROM AUTHOR]

Hyperuricemia is a metabolic disease caused by purine nucleotide metabolism disorder. The prevalence of hyperuricemia is increasing worldwide, with a growing trend in the younger populations. Although numerous studies have indicated that hyperuricemia may be an independent risk factor for insulin resistance, the causal relationship between the two is controversial. There are few reviews, however, focusing on the relationship between uric acid (UA) and insulin resistance from experimental studies. In this review, we summarized the experimental models related to soluble UA-induced insulin resistance in pancreas and peripheral tissues, including skeletal muscles, adipose tissue, liver, heart/cardiomyocytes, vascular endothelial cells and macrophages. In addition, we summarized the research advances about the key mechanism of UA-induced insulin resistance. Moreover, we attempt to identify novel targets for the treatment of hyperuricemia-related insulin resistance. Lastly, we hope that the present review will encourage further researches to solve the chicken-and-egg dilemma between UA and insulin resistance, and provide strategies for the pathogenesis and treatment of hyperuricemia related metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. Case presentation: The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient's symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient's condition. Conclusion: If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient's condition is critical, and early diagnosis will lead to a favorable outcome for the patient. [ABSTRACT FROM AUTHOR]

The influence of repeated lockdowns on mental health and social isolation is unknown. We conducted a longitudinal study of the influence of repeated mild lockdowns during two emergency declarations in Japan, in May 2020 and February 2021. The analyses included 7893 people who participated in all online surveys. During repeated mild lockdowns, mental and physical symptoms decreased overall, while loneliness increased and social networks decreased. Subgroup analyses revealed that depression and suicidal ideation did not decrease only in the younger age group (aged 18–29 years) and that younger and middle-aged people (aged 18–49 years), women, people with a history of treatment for mental illness, and people who were socially disadvantaged in terms of income had higher levels of mental and physical symptoms at all survey times. Additionally, comprehensive extraction of the interaction structure between depression, demographic attributes, and psychosocial variables indicated that loneliness and social networks were most closely associated with depression. These results indicate that repeated lockdowns have cumulative negative effects on social isolation and loneliness and that susceptible populations, such as young people and those with high levels of loneliness, require special consideration during repeated lockdown situations. [ABSTRACT FROM AUTHOR]

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a WHO grade II and III tumor arising from pineal parenchymal cells. PPTID is a rare tumor accounting for less than 1% of all primary central nervous system neoplasms. Therefore, reports describing the clinical characteristics and biological features of PPTID are lacking. Moreover, the therapeutic strategy remains controversial. The current study aimed to evaluate treatment results and problems of contemporary therapeutic modalities of PPTID based on its features compared with other pineal parenchymal tumors. A comprehensive systematic literature review of 69 articles was performed, including articles on PPTID (389 patients) and similar tumors. Patient demographics, disease presentation, imaging characteristics, biological features, and current therapeutic options and their results were reviewed. We found that histopathological findings based on current WHO classification are well associated with survival; however, identifying and treating aggressive PPTID cases with uncommon features could be problematic. A molecular and genetic approach may help improve diagnostic accuracy. Therapeutic strategy, especially for grade III and aforementioned uncommon and aggressive tumors, remains controversial. A combination therapy involving maximum tumor resection, chemotherapy, and radiotherapy could be the first line of treatment. However, although challenging, a large prospective study would be required to identify ways to improve the clinical results of PPTID treatment. [ABSTRACT FROM AUTHOR]

Previous findings on relationships between inhibition that is a core executive function, and trait rumination have been inconsistent. This inconsistency could be overcome by investigating the association between rumination and the two subcomponents of inhibition: response inhibition and attentional inhibition. This study examined whether and how response inhibition and attentional inhibition were related to rumination as well as worry. University students in Japan (N = 213) conducted the Go/No-Go Task and the Modified Stroop Task. They also completed self-report measures of depression, trait rumination, trait worry, stressors, and aggressive behaviors. Results indicated that response inhibition deficits were positively associated with trait rumination, and this association was mediated by increases in aggressive behaviors and interpersonal stressors. The associations between these variables remained significant even after controlling for depression level. There were no significant direct or indirect associations between attentional inhibition deficits and rumination. These results suggest that response inhibition deficits, among the subcomponents of inhibition, have an indirect positive association with rumination through interpersonal processes. Results also showed nonsignificant differences between rumination and worry in the magnitude of correlation coefficients with the two subcomponents of inhibition. Therefore, it remains unclear whether the positive association with response inhibition is unique to rumination. [ABSTRACT FROM AUTHOR]

Attribute-based medicine is essential for patient-centered medicine. To date, the groups of patients with chronic kidney disease (CKD) requiring urate-lowering therapy are clinically unknown. Herein, we evaluated the efficacy of febuxostat using a cross-classification, attribute-based research approach. We performed post hoc analysis of multicenter, randomized, double-blind, placebo-controlled trial data for 395 patients with stage 3 CKD and asymptomatic hyperuricemia. Participants were divided into febuxostat or placebo groups and subcohorts stratified and cross-classified by proteinuria and serum creatinine concentrations. In patients stratified based on proteinuria, the mean eGFR slopes were significantly higher in the febuxostat group than in the placebo group (P = 0.007) in the subcohort without proteinuria. The interaction between febuxostat treatment and presence of proteinuria in terms of eGFR slope was significant (P for interaction = 0.019). When cross-classified by the presence of proteinuria and serum creatinine level, the mean eGFR slopes significantly differed between the febuxostat and placebo groups (P = 0.040) in cross-classified subcohorts without proteinuria and with serum creatinine level ≥ median, but not in the cross-classified subcohorts with proteinuria and serum creatinine level < median. Febuxostat mitigated the decline in kidney function among stage 3 CKD patients with asymptomatic hyperuricemia without proteinuria. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of tibial tunnel coalition on knee rotatory laxity and clinical outcomes after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. Methods: Forty-one patients who underwent anatomic DB ACL reconstruction were included prospectively. Three-dimensional computed tomography of the knee joint was obtained at approximately 1 year postoperatively to determine if tunnel coalition occurred. After excluding seven cases of femoral tunnel coalition, two groups were established based on the existence of a tibial tunnel coalition. The pivot-shift test was quantitatively evaluated on the basis of tibial acceleration preoperatively and at 1 year postoperatively. Two subjective scores, the International Knee Documentation Committee (IKDC) subjective and Lysholm scores, were also collected. The pivot-shift measurement and subjective scores were compared between the ACL-reconstructed knees with and without tibial tunnel coalition. The independent t test, Pearson's chi-square test, and Student t tests were used in data analysis. Results: Twenty-one knees had tibial tunnel coalition (group C), whereas 13 knees did not have tunnel coalition(group N). Pivot-shift was significantly diminished postoperatively in both groups on the basis of the clinical examination and quantitative evaluations (p < 0.05). However, there was a small but significant difference in tibial acceleration demonstrating larger pivot-shift in group C (1.0 ± 0.6 m/s2) than in group N (0.5 ± 0.3 m/s2, p < 0.05). No significant difference was observed in the IKDC subjective and Lysholm scores (both n.s.). Conclusion: When the tibial tunnel coalition occurs after DB ACL reconstruction, knee rotatory laxity may not be restored in ACL-reconstructed knees, as expected in those without tunnel coalition. It is recommended that two tibial tunnels should be created separately when performing DB-ACL reconstruction to achieve better control of rotatory knee laxity. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations. [ABSTRACT FROM AUTHOR]

Introduction: Poor medication adherence and disordered eating are major self-care problems in patients with type 2 diabetes that worsen glycemic control and increase the risk of developing severe diabetes complications. Affective temperament, which remains mostly unchanged throughout life, is speculated to predict poor treatment response and high comorbidity. The aim of this study was to explore the link between affective temperament and poor glycemic control due to insufficient self-care. Methods: This single-center case–control study involved 77 outpatients divided into the 'poor glycemic control' group (n = 52) and the 'better glycemic control' group (n = 25) based on their mean glycated hemoglobin (HbA1c) levels over the past 12 months. All participants underwent one-on-one interviews during which they completed the following psychometric questionnaires: (1) the Mini-International Neuropsychiatric Interview 5.0.0; (2) the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire; (3) a researcher-designed single question for assessing subclinical stress-induced overeating; and (4) the Morisky Medication Adherence Scale. The difference between two continuous independent variables was determined using Student's t test. Discrete variables were compared using the Chi-square (χ2) or Fisher's exact test. Multiple testing corrections were performed using the false discovery rate. Results: Those outpatients in the poor glycemic control group exhibited significantly more stress-induced overeating (χ2 = 1.14, q statistic = 0.040) and poor medication adherence (t = 3.70, q = 0.034) than those in the better glycemic control group. However, there were no significant differences between the two groups in terms of affective temperaments, clinical eating disorders, or diabetes-specific distress. Patients with stress-induced overeating (t = − 2.99, p = 0.004) and poor medication adherence (t = − 4.34, p = 0.000) exhibited significantly higher scores for cyclothymic temperament than their counterparts. Conclusion: Cyclothymic temperament is significantly associated with disordered eating and/or poor medication adherence in patients with type 2 diabetes and is possibly linked to poor glycemic control. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a highly aggressive, extra-nodal non-Hodgkin lymphoma that is confined to the central nervous system (CNS) and the eyes. Most PCNSLs arise in immunocompetent older patients and less frequently in immunocompromised patients with Epstein-Barr virus infection. Although a patient's initial response to chemotherapy and radiation therapy is favorable, the clinical outcome of PCNSL remains poor compared to that of systemic lymphoma. Radiation-induced neurotoxicity is also a critical problem for patients with PCNSL. Therefore, a novel therapeutic strategy is required to overcome these challenges. Recent studies have largely uncovered the genomic landscape and associated histopathological features of PCNSL. Based on this background, novel therapeutic agents, such as Bruton's tyrosine kinase inhibitors and immune checkpoint inhibitors, have been introduced for patients with PCNSL. Here, we provide an overview of the updated histopathological and genomic characterization of PCNSL and summarize the current therapeutic strategies. We also review current preclinical PCNSL models for translational research. [ABSTRACT FROM AUTHOR]

Introduction: Sodium glucose co-transporter 2 (SGLT2) inhibitors are widely used in the management of type 2 diabetes mellitus; they prevent cardiovascular events and reduce fat mass. However, little is known about the effects of SGLT2 inhibitors on type 1 diabetes mellitus as an adjuvant to insulin therapy. Therefore, we aimed to elucidate the effects of SGLT2 inhibitors on body composition of patients with type 1 diabetes mellitus and assess blood glucose variability. Methods: A single-center, single-arm, prospective, interventional study was performed on Japanese patients with type 1 diabetes mellitus who were not administered SGLT2 inhibitors prior to this study. These patients were equipped with flash glucose monitoring (FGM) and administered ipragliflozin 50 mg daily. Body composition was evaluated using bioelectrical impedance analysis, and glycemic variabilities were assessed using FGM before and after SGLT2 inhibitor treatment. Results: After 52 weeks of treatment, the total fat mass tended to be reduced (− 9.10% from baseline, P = 0.098). In addition, skeletal muscle mass also decreased (− 2.98% from baseline, P = 0.023). Although the basal insulin dose was reduced, SGLT2 inhibitors decreased HbA1c levels. FGM revealed that glycemic variabilities were also reduced, and time within the target glucose range increased (51.7% vs. 62.5%, P = 0.004). Conclusion: SGLT2 inhibitors have beneficial effects on glycemic variabilities and fat mass reductions in patients with type 1 diabetes mellitus. However, loss of skeletal muscle is a major concern; therefore, caution is required when using SGLT2 inhibitors in lean patients with type 1 diabetes mellitus. Trial registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN000042407). [ABSTRACT FROM AUTHOR]

Movies depicting certain types of motion often provoke uncomfortable symptoms similar to motion sickness, termed visually induced motion sickness (VIMS). VIMS generally evolves slowly during the viewing of a motion stimulus and, when the stimulus is removed, the recovery proceeds over time. Recent human neuroimaging studies have provided new insights into the neural bases of the evolution of VIMS. In contrast, no study has investigated the neural correlates of the recovery from VIMS. Study of the recovery process is critical for the development of a way to promote recovery and could provide further clues for understanding the mechanisms of VIMS. We thus investigated brain activity during the recovery from VIMS with functional connectivity magnetic resonance imaging. We found enhanced recovery-related functional connectivity patterns involving brain areas such as the insular, cingulate and visual cortical regions, which have been suggested to play important roles in the emergence of VIMS. These regions also constituted large interactive networks. Furthermore, the increase in functional connectivity was correlated with the subjective awareness of recovery for the following five pairs of brain regions: insula–superior temporal gyrus, claustrum–left and right inferior parietal lobules, claustrum–superior temporal gyrus and superior frontal gyrus–lentiform nucleus. Considering the previous findings on the functions of these regions and the present results, it is suggested that the increase in FC may reflect brain processes such as enhanced interoceptive awareness to one's own bodily state, a neuroplastic change in visual-processing circuits and/or the maintenance of visual spatial memory. [ABSTRACT FROM AUTHOR]

Introduction: In Japan, several sodium glucose co-transporter 2 (SGLT2) inhibitors have been used for type 1 diabetes mellitus as an adjuvant therapy to insulin therapy; however, there are no clinical reports regarding the satisfaction of its use. Therefore, we conducted a survey among patients with type 1 diabetes undergoing treatment using an SGLT2 inhibitor. Methods: This is a single-arm open-label prospective study including 24 patients with type 1 diabetes who were to be initiated on ipragliflozin treatment between March and August 2019. All participants provided written informed consent. They completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ) for the survey and 3 months of observation after the administration of an SGLT2 inhibitor (50 mg of ipragliflozin), and changes from baseline diabetes treatment satisfaction were evaluated using modified DTSQ scores (five-step evaluation) and were analyzed. Results: The average score for each question on DTSQ significantly increased [mean (standard deviation); 0.25 (0.25) vs 0.83 (0.77), P = 0.004]. Approximately 75% of the patients perceived an improvement in glycemic control over short periods of time. Finally, 54.2% of patients were highly satisfied and would recommend the SGLT2 inhibitor treatment [0.0 (0.0) vs. 0.92 (1.32), P < 0.001]. After the administration of ipragliflozin, reductions in body weight [24.0 (2.9) vs. 23.4 (2.9) kg/m2, P = 0.002], total insulin [39.1 (12.9) vs. 34.3 (12.5) units, P = 0.013], and glycated hemoglobin [7.77 (0.97) vs. 7.40 (0.86) %, P = 0.013] were observed, without any severe side effects. Improvements in glycemic variability indexes were observed through flash glucose monitoring. Conclusions: SGLT2 inhibitors may improve clinical treatment satisfaction by improving glycemic variability in patients with type 1 diabetes mellitus, while not inducing severe side effects with careful use. Trial Registration: This study is registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000040487). [ABSTRACT FROM AUTHOR]

Two Staphylococcus aureus bacteriophages, KSAP7 and KSAP11, were isolated from sewage and characterized. Based on morphology and DNA sequences, they were assigned to the genus Silviavirus, subfamily Twortvirinae, family Herelleviridae, whose members are hypothesized to be suitable for bacteriophage therapy. The KSAP7 and KSAP11 genomes were 137,950 and 138,307 bp in size, respectively. Although their DNA sequences were almost identical, evidence of site-specific DNA rearrangements was found in two regions. Changes in the number of PIEPEK amino acid sequence repeats encoded by orf10 and the insertion/deletion of a 541-bp sequence that includes a possible tail-related gene were identified. [ABSTRACT FROM AUTHOR]

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily. [ABSTRACT FROM AUTHOR]

Rationale: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. Objectives: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. Methods: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. Results: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. Conclusions: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation. [ABSTRACT FROM AUTHOR]

Phytophagous insects are among the most diverse of the earth's organisms, and their diversification patterns and the driving forces behind these have attracted considerable research interest. Host shifting to closely related plant species is thought to play an important role in phytophagous insect diversification, but the extent to which other interactions such as mutualistic associations affect diversification is not yet known. In this study, we reconstructed the molecular phylogeny of Japanese Stomaphis aphids and determined whether host shifting or mutualistic association with different ant species could explain diversification in this aphid genus. We analyzed 12 species of Stomaphis and grouped them into ten well-supported DNA lineages. Species in each lineage used a single or a few host plant species, but were mutualistically associated with many ant species of the genus Lasius. This result suggests that Stomaphis evolutionarily diversified primarily through host plant shifts. Interestingly, the reconstructed phylogeny suggests that Stomaphis host shifts occasionally occurred between very distantly related host plant taxa (spanning up to five plant orders). The dependence of Stomaphis on long-lasting Lasius ant colonies situated in temperate deciduous forests where Lasius is the dominant ant genus may have led the aphids to shift to distantly related but spatially adjacent host tree species. [ABSTRACT FROM AUTHOR]

Inositol hexaphosphate (IP6), a food constituent with various health benefits, has been shown to suppress postprandial elevations of serum uric acid (SUA) levels in healthy adults by inhibiting purine nucleoside and base absorption. Here, we investigated the effect of repeated intake of IP6 on fasting SUA levels in hyperuricemic subjects. This randomized double-blind placebo-controlled crossover design study included 31 asymptomatic hyperuricemic subjects (fasting SUA level > 7.0 but <9.0 mg/dL). Subjects ingested placebo or IP6 drinks (600 mg twice daily) during two 2-week intervention periods with a 2-week washout period. The primary outcome was fasting SUA level; the secondary outcome was the urinary uric acid to creatinine ratio. Fasting SUA levels in the IP6 group were lower than those in the placebo group (p < 0.05). The urinary uric acid to creatinine ratio did not change between the placebo and IP6 groups (p > 0.05). This study showed that a 2-weeks supplementation period of 600 mg IP6 twice daily can improve fasting SUA levels in hyperuricemic subjects. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (PLGGs) have relatively favorable prognosis and some resectable PLGGs, such as cerebellar pilocytic astrocytoma, can be cured by surgery alone. However, many PLGG cases are unresectable and some of them undergo tumor progression. Therefore, a multidisciplinary approach is necessary to treat PLGG patients. Recent genomic analysis revealed a broad genomic landscape underlying PLGG. Notably, the majority of PLGGs present MAPK pathway-associated genomic alterations and MAPK signaling-dependent tumor progression. Following preclinical evidence, many clinical trials based on molecular target therapy have been conducted on PLGG patients, some of whom exhibited durable response to target therapy. Here, we provide an overview of PLGG genetics and the evidence supporting the application of molecular target therapy in these patients. [ABSTRACT FROM AUTHOR]

Purpose of review: To trace the influence of disc hemorrhage studies on our understanding of glaucoma.Sources: Major articles published during the last 50 years since the rediscovery of disc hemorrhage were identified. A total of 196 articles were selected from 435 articles retrieved using the keywords glaucoma and disc hemorrhage as of August 9 2018 from PubMed.Recent findings: The main characteristics of disc hemorrhage, including its morphology, recurrence rate, duration, increased incidence in glaucoma, and role in the progression of normal tension glaucoma was well understood by the year 2000. Since then, studies have focused on more sophisticated and accurate methods of elucidating both structural and functional progression, with special attention to the role of the lamina cribrosa. Nevertheless, both the mechanism of disc hemorrhage development and its fuller relationship with glaucoma remain unclear.Summary: Disc hemorrhage research requires careful study of glaucomatous optic neuropathy. This has been facilitated by recent advances in optical coherence tomography (OCT) angiography and other OCT technologies. Furthermore, animal studies of disc hemorrhage promise new insights into glaucomatous optic neuropathy. [ABSTRACT FROM AUTHOR]

Purpose: To determine the clinical features of patients diagnosed with superior segmental optic hypoplasia (SSOH) and to quantitatively compare retinal nerve fiber layer (RNFL) thickness in SSOH eyes, to that in normal subjects.Study design: Retrospective comparative case series.Methods: We examined the medical charts of 106 eyes of 59 patients with SSOH and 35 eyes of 35 normal subjects as controls. Forty-four of 59 patients had been examined by spectral-domain optical coherence tomography (SD-OCT). Eyes with SSOH were classified into a definite and a suspect type determined by standard automated perimetry. The definite type had inferior visual field (VF) defects, while the suspect type did not have inferior VF defects. The findings of the SD-OCT images of 35 eyes with SSOH were compared to those of the 35 normal eyes.Results: Of the 106 eyes with SSOH, 56 (52.8%) were classified as the definite type and 50 (47.2%) as the suspect type. OCT showed that the average of the total RNFL thickness was significantly thinner in the SSOH group than in the normal group (P < 0.001; Mann-Whitney U test). Sectorial analysis demonstrated that the RNFL was thinner than controls in all quadrants (all P < 0.001; Mann-Whitney U test). The comparison of the hourly sectors showed that the RNFL was thinner at 10, 11, 12, 1, 2, 3, 5, and 6 o'clock sectors in the SSOH group than controls.Conclusions: Approximately one-half of eyes with SSOH had a detectable VF defect. OCT showed that eyes with SSOH have a thinner RNFL than controls except in 4 o'clock and from 7 o'clock to 9 o'clock. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with 89Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. 89Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with 89Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of 89Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using 89Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma. [ABSTRACT FROM AUTHOR]

Specific design features and main characteristics of a compact accelerator-based epithermal neutron source for boron neutron capture therapy are described. High quality of the neutron flux generated by the accelerator-based source has been experimentally confirmed. The opportunities for medical use of the accelerator-based epithermal neutron source in oncological centers for boron neutron capture therapy are assessed. [ABSTRACT FROM AUTHOR]

Reports on the incidence of persistent left superior vena cava (PLSVC) in the normal population are limited to studies involving pacemaker implantation candidates and cadavers. The incidence in patients with congenital heart diseases (CHDs) is estimated to be higher than that in the normal population; however, the details are unclear. To investigate the incidence of PLSVC in the normal population and in patients with CHDs, subjects were examined prospectively using echocardiography. Normal subjects consisted of 2841 successive neonates without intra-cardiac or congenital anomalies born in Gifu Prefectural General Medical Center. Additionally, 1920 patients with CHDs were evaluated. The incidence of PLSVC in normal neonates was 0.21% (95% confidence interval 0.042-0.38%). A high incidence (more than 7.0 times the incidence in normal subjects) was observed in all CHD patients. The high incidence group included coarctation of the aorta (CoA) (23.7%) and double outlet right ventricle (DORV) patients (24.6%). The second group consisted of CHD patients with ventricular septal defect (VSD), with an incidence ranging from 5.1 to 6.1%. The low incidence group comprised patients with other CHDs, with an incidence between 1.5 and 3.1%. The incidence of PLSVC in trisomy 21 and atrial septal defect patients was significantly higher than that in normal neonates. The incidence of PLSVC in the normal population and in patients with CHDs was systematically evaluated for the first time. The incidence in CHD patients appeared to be positively influenced by the type of CHD, particularly by DORV, CoA, and VSD. [ABSTRACT FROM AUTHOR]