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The twisted conformer of bistricyclic aromatic enes (BAEs) has a small HOMO–LUMO gap owing to the twisted double bond. In this study, we synthesized diphenoquinones fused with thiophene rings as a new twisted conformer-predominant BAE. They exhibited deep LUMO energy levels and apparent n-type semiconductor properties. [ABSTRACT FROM AUTHOR]

Background: Cardiac neoplasms may cause life-threatening symptoms associated with cerebral infarction, ventricular arrhythmias, and heart failure. Emergency surgery or preoperative treatment may be required for these patients. However, no study has reported the surgical outcomes in cases involving cardiac neoplasms with life-threatening complications. The current study investigated the mid- to long-term outcomes of surgery in patients with cardiac neoplasms in life-threatening conditions. Methods: This study retrospectively analyzed 36 consecutive patients who underwent resection for cardiac neoplasms with life-threatening cardiovascular, respiratory, and cerebral nervous system complications from January 2000 to December 2022. Their mean age at surgery was 54.9 years. In terms of fatal events, one patient who experienced a ventricular tachycardia storm caused by a left ventricular neoplasm was placed under deep sedation and managed with a ventilator preoperatively. Seven patients who presented with limb motor paralysis and visual defects had cerebral infarction. Two of the seven patients with cerebral infarction received cerebrovascular treatment before cardiac surgery. Results: During the follow-up period, cerebral- and cardiovascular-related deaths were not recorded. All postoperative cerebral and cardiovascular complications were new-onset cerebral infarction (n = 2) (with symptoms that improved during the long term). The mean follow-up period was 6.2 years. The 5- and 10-year survival rates of all patients were 89.8% and 78.7%, respectively. There were no significant differences in postoperative prognosis between patients with preoperative cerebral infarctions and those without. Conclusions: The long-term surgical outcome of patients with life-threatening symptomatic cardiac neoplasm was good. Thus, preoperative complications did not affect prognosis. [ABSTRACT FROM AUTHOR]

Glucose-dependent insulinotropic polypeptide (GIP) of the incretin group has been shown to exert pleiotropic actions. There is growing evidence that advanced glycation end products (AGEs), senescent macromolecules formed at an accelerated rate under chronic hyperglycemic conditions, play a role in the pathogenesis of atherosclerotic cardiovascular disease in diabetes. However, whether and how GIP could inhibit the AGE-induced foam cell formation of macrophages, an initial step of atherosclerosis remains to be elucidated. In this study, we address these issues. We found that AGEs increased oxidized low-density-lipoprotein uptake into reactive oxygen species (ROS) generation and Cdk5 and CD36 gene expressions in human U937 macrophages, all of which were significantly blocked by [D-Ala2]GIP(1–42) or an inhibitor of NADPH oxidase activity. An inhibitor of AMP-activated protein kinase (AMPK) attenuated all of the beneficial effects of [D-Ala2]GIP(1–42) on AGE-exposed U937 macrophages, whereas an activator of AMPK mimicked the effects of [D-Ala2]GIP(1–42) on foam cell formation, ROS generation, and Cdk5 and CD36 gene expressions in macrophages. The present study suggests that [D-Ala2]GIP(1–42) could inhibit the AGE-RAGE-induced, NADPH oxidase-derived oxidative stress generation in U937 macrophages via AMPK activation and subsequently suppress macrophage foam cell formation by reducing the Cdk5-CD36 pathway. [ABSTRACT FROM AUTHOR]

Background Long-term care (LTC) costs create burdens on aging societies. Maintaining oral health through dental visits may result in shorter LTC periods, thereby decreasing LTC costs; however, this remains unverified. We examined whether dental visits in the past 6 months were associated with cumulative LTC insurance (LTCI) costs. Methods This cohort study of the Japan Gerontological Evaluation Study targeted independent adults aged≥65 years in 2010 over an 8-year follow-up. We used data from a self-reported questionnaire and LTCI records from the municipalities. The outcome was cumulative LTCI costs, and exposure was dental visits within 6 months for prevention, treatment, and prevention or treatment. A 2-part model was used to estimate the differences in the predicted cumulative LTCI costs and 95% confidence intervals (CIs) for each dental visit. Results The mean age of the 8 429 participants was 73.7 years (standard deviation [ SD ] = 6.0), and 46.1% were men. During the follow-up period, 17.6% started using LTCI services. The mean cumulative LTCI cost was USD 4 877.0 (SD  = 19 082.1). The predicted cumulative LTCI costs were lower among those had dental visits than among those who did not. The differences in predicted cumulative LTCI cost were −USD 1 089.9 (95% CI = −1 888.5 to −291.2) for dental preventive visits, −USD 806.7 (95% CI = −1 647.4 to 34.0) for treatment visits, and −USD 980.6 (95% CI = −1 835.7 to −125.5) for preventive or treatment visits. Conclusions Dental visits, particularly preventive visits, were associated with lower cumulative LTCI costs. Maintaining oral health through dental visits may effectively reduce LTCI costs. [ABSTRACT FROM AUTHOR]

Background We previously reported that normalization of motor evoked potential (MEP) monitoring amplitude by compound muscle action potential (CMAP) after peripheral nerve stimulation prevented the expression of anesthetic fade (AF), suggesting that AF might be due to reduced synaptic transfer in the neuromuscular junction. Methods We calculated the time at which AF began for each of craniotomy and spinal cord surgery, and examined whether AF was avoided by CMAP after peripheral nerve stimulation normalization in each. Similar studies were also made with respect to the upper and lower limb muscles. Results AF was observed in surgery lasting 160 minutes for craniotomy and 260 minutes or more for spinal surgery, and 195 minutes in the upper limb muscles and 135 minutes in the lower limb muscles. In all the series, AF could be avoided by CMAP after peripheral nerve stimulation normalization. Conclusion AF of MEP occurred in both craniotomy and spinal cord surgery, and it was also corrected by CMAP after peripheral nerve stimulation. AF is considered to be mainly due to a decrease in synaptic transfer of the neuromuscular junction due to the accumulation of propofol because of the avoidance by CMAP normalization. However, it may be partially due to a decrease in the excitability of pyramidal tracts and α-motor neurons, because AF occurred earlier in the lower limb muscles than in the upper limb muscles. [ABSTRACT FROM AUTHOR]

We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.

Oral health is essential for nutritional status; however, little is known about its association with weight change. This study aimed to investigate whether the risk of weight change differs according to the presence of each important component of oral hypofunction (fewer remaining teeth, low chewing efficiency, swallowing problems, and xerostomia) among independent older adults. This was a three-year follow-up cohort study based on self-reported questionnaires. The participants were independent older adults aged ≥65 from the Japan Gerontological Evaluation Study (JAGES). We used >5% weight loss/gain during follow-up as the outcome variables, and the number of remaining teeth (≥20/10–19/0–9), the presence of chewing difficulty, swallowing problems, and xerostomia (yes/no) as the exposure variables. We fitted the Poisson regression model, including possible confounders to estimate the risk ratios (RRs) and 95% confidence intervals (CIs). For weight loss, RRs were significantly higher among those with 0–9 remaining teeth (RR = 1.17; 95% CI = 1.11–1.23), chewing difficulty (RR = 1.12; 95% CI = 1.07–1.16), and xerostomia (RR = 1.11; 95% CI = 1.06–1.16), but there was no significant association with swallowing problems (RR = 1.01; 95% CI = 0.97–1.06). For weight gain, we also found similar associations with oral hypofunction. Oral hypofunction among older adults could have non-negligible health impacts on nutritional status.

Abstract A 47‐year‐old male with paroxysmal nocturnal haemoglobinuria (PNH) controlled with routine ravulizumab administration suffered a massive haemolytic crisis due to choledocholithiasis. Laparoscopic cholecystectomy was performed 6 weeks after a regular ravulizumab infusion. After surgery, the patient presented with anaemia without marked elevation in lactate dehydrogenase and required two blood transfusions. Tumour necrosis factor‐α increased more than twofold with reticulocyte suppression after surgery, suggesting the involvement of myelosuppressive cytokines. This case suggests that laparoscopic surgery may be safely performed in patients with PNH receiving ravulizumab maintenance treatment. However, attention should be paid to postoperative anaemia, regardless of breakthrough haemolysis.

Abstract Adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by white matter degeneration caused by adenosine triphosphate‐binding cassette subfamily D member 1 (ABCD1) gene mutations, which lead to an accumulation of very‐long‐chain fatty acids (VLCFA). Hematopoietic stem cell transplantation (HSCT) is the most effective treatment; however, the ratio of donor‐to‐recipient cells required to prevent the progression of demyelination is unclear. The proband was diagnosed with the childhood cerebral form of ALD at 5 years of age based on the clinical phenotype, elevated plasma VLCFA levels, and pathogenic ABCD1 mutation c.293C>T (p.Ser98Leu). Soon after the diagnosis, he became bedridden. At 1 year of age, his younger brother was found to carry the same ABCD1 mutation; despite being asymptomatic, at 1 year and 9 months, head magnetic resonance imaging (MRI) showed high‐signal‐intensity lesions in the cerebral white matter. The patient underwent unrelated cord blood transplantation (UCBT) with a reduced conditioning regimen, which resulted in mixed chimerism. For 7 years after UCBT, the donor chimerism remained low (

Semen analysis has long been used to evaluate male fertility. Recently, several sperm function tests have been developed. Of those, the sperm DNA fragmentation index (DFI), which describes the status of the sperm DNA, is thought to be a suitable parameter for evaluating male fertility. However, there have been no large-scale studies on the sperm DFI of Japanese men. Therefore, we investigated the feasibility of using an in-house flow cytometry-based sperm DFI analysis based on the sperm DNA fragmentation test of sperm chromatin structure assay (SCSA) to assess male fertility in Japan. This study enrolled 743 infertile and 20 fertile Japanese men. To evaluate reproducibility, inter- and intraobserver precision was analyzed. A receiver operating characteristic curve analysis was used to set a cutoff value for the sperm DFI to identify men who could father children by timed intercourse or intrauterine insemination. The variability of the sperm DFI among fertile volunteers was determined. The relationship between semen parameters and the sperm DFI was assessed by Spearman's rho test. A precision analysis revealed good reproducibility of the sperm DFI. The cutoff value of sperm DNA fragmentation in infertile men was 24.0%. Semen volume had no relationship with the sperm DFI. Sperm concentration, sperm motility, total motile sperm count, and percentage of normal-shaped sperm were significantly and negatively correlated with the sperm DFI. The median sperm DFI was smaller in fertile volunteers (7.7%) than that in infertile men (19.4%). Sperm DNA fragmentation analysis can be used to assess sperm functions that cannot be evaluated by ordinary semen analysis.

It has been reported that some specific changes in DNA methylation can be due to aging or infection by tumor-related viruses but the effect of herpes simplex virus type 1 (HSV-1) in this regard is unknown. HSV-1 is a well-known virus that causes cold sores. After the primary infection, the virus switches to latent infection and remains in the body for the whole life. As the location of DNA methylation, we focused on the promoter region of the COASY gene, which codes for coenzyme A synthase, because methylation in this region is reportedly associated with Alzheimer's disease (AD). During HSV-1 lytic infection, compared to non-infected cells, COASY DNA methylation decreased but when HSV-1 replication was inhibited by acyclovir, an anti-herpes agent, COASY DNA methylation increased. In addition, for expression of immediate early protein only, there was no significant change in COASY DNA methylation, while for expression of the capsid protein VP26, a late protein known to bind with DNA methyltransferase DNMT3A, in the nucleus only, COASY DNA methylation significantly increased compared to the control, without changes in DNMT3A mRNA. Our results suggested that DNA methylation occurred not due to transcriptional changes in DNMT3A but through translational regulation. In this research, we showed that host COASY DNA methylation is altered by HSV-1 infection, in particular by HSV-1 VP26. It is a potential cause of various diseases, and this is particularly relevant for AD.

Abstract TUBB4A gene variants cause dystonia type 4 and hypomyelination with atrophy of the basal ganglia and cerebellum. We report the case of a child with delayed motor development, intellectual disability, and dystonia. Magnetic resonance imaging revealed hypomyelination and progressive cerebellar atrophy without atrophy of the basal ganglia. Whole-exome sequencing revealed a de novo heterozygous variant, c.1088T > C, p.(Met363Thr), in TUBB4A. The present case further supports the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants.