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We describe a successful surgical technique of abdominal trachelectomy and re‐vaginoplasty for cervico‐vaginal stenosis following unsuccessful uterovaginal anastomosis and vaginoplasty in a patient with congenital cervical and vaginal aplasia. After the surgical procedure, cervico‐vaginal stenosis was resolved and periodic menstruation without dysmenorrhoea resumed. While long‐term follow‐up is essential to ensure successful pregnancy and delivery, we conclude that this novel surgical procedure is a promising alternative for improvement of the quality of life and normal sexual function, and for preservation of fertility in patients with cervical and vaginal aplasia. [ABSTRACT FROM AUTHOR]

Collisions of birds, especially endangered species, with wind turbines is a major environmental concern. Automatic bird monitoring can be of aid in resolving the issue, particularly in environmental risk assessments and real-time collision avoidance. For automatic recognition of birds in images, a clean, detailed, and realistic dataset to learn features and classifiers is crucial for any machine-learning-based method. Here, we constructed a bird image dataset that is derived from the actual environment of a wind farm and that is useful for examining realistic challenges in bird recognition in practice. It consists of high-resolution images covering a wide monitoring area around a turbine. The birds captured in these images are at relatively low resolution and are hierarchically labeled by experts for fine-grained species classification. We conducted evaluations of state-of-the-art image recognition methods by using this dataset. The evaluations revealed that a deep-learning-based method and a simpler traditional learning method were almost equally successful at detection, while the former captures more generalized features. The most promising results were provided by the deep-learning-based method in classification. The best methods in our experiments recorded a 0.98 true positive rate for bird detection at a false positive rate of 0.05 and a 0.85 true positive rate for species classification at a false positive rate of 0.1. [ABSTRACT FROM AUTHOR]

Aim Autofluorescence imaging (AFI) is a novel technology for endoscopy, which enhances neoplastic lesions of the gastrointestinal tract. The aim of this investigation was to examine whether AFI colonoscopy can identify dysplasia in ulcerative colitis. Method We examined 48 patients with ulcerative colitis by AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding lesions under conventional colonoscopy were observed by AFI. Those target areas were classified into low AF and high AF according to the colour under AFI colonoscopy. The grade of dysplasia was determined in the specimens obtained from the target areas. Results About 126 sites (35 protruding lesions and 91 flat areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas and to be low in 84 areas. The positive rate of dysplasia was higher in protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive dysplasia was not statistically different between lesions determined to be low AF (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in protruding lesions was significantly higher in low AF than in high AF (45.0% vs 13.3%, P = 0.043), while the value in flat lesions was not different between low AF and high AF (8.2% vs 0%, P = 0.3). Conclusions Autofluorescence imaging colonoscopy seems to have a role for the detection of dysplaia in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Sekita A, Ninomiya T, Tanizaki Y, Doi Y, Hata J, Yonemoto K, Arima H, Sasaki K, Iida M, Iwaki T, Kanba S, Kiyohara Y. Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese community: the Hisayama Study. Objective: To examine secular trends in the prevalence of Alzheimer’s disease (AD) and vascular dementia (VD) in a general Japanese population. Method: Four cross-sectional examinations were conducted among residents of a Japanese community aged ≥65 in 1985, 1992, 1998 and 2005. Results: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). Conclusion: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population. [ABSTRACT FROM AUTHOR]

Background Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin. Methods Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope 13C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of 13CO2 in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers). Results Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal ( r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying ( versus peak excretion time r = − 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index. Conclusions Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The present study was undertaken to elucidate germ line mutations of the base excision repair gene, MUTYH, in Japanese patients with adenomatous polyposis. We screened germ line mutations of adenomatous polyposis coli ( APC) gene and MUTYH in 66 Japanese patients with adenomatous polyposis. APC was screened by the protein truncation test, while MUTYH was screened by polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing. The nicking assay was applied in order to evaluate the DNA glycosylase activity of the identified MUTYH variant. In this study, Seven MUTYH variants were identified in 16 of 21 APC-negative patients. Q324H mutation was the most frequent mutation, with an allele frequency of 49%. Two patients carried biallelic mutations other than Q324H; a patient had biallelic G272E and A359V mutations, while the other had compound heterozygotes of P18L and G25D mutations. Nicking assay for G272E using the corresponding mouse MUTYH mutant with G257E revealed that G272E is a variant to cause an impaired DNA glycosylase activity. Homozygous MUTYH mutation accounts for approximately 10% of Japanese patients with adenomatous polyposis. G272E may be one of the mutations specific to patients with adenomatous polyposis in East Asia. [ABSTRACT FROM AUTHOR]

Background and purpose:Secretory phospholipase A2 (sPLA2) is implicated in atherosclerosis, although the effects of specific sPLA2 inhibitors have not been studied. We investigated the effects of the indole analogue indoxam on low-density lipoprotein (LDL) modification by sPLA2 enzymes of different types and on the associated inflammatory responses in human umbilical vein endothelial cells (HUVEC).Experimental approach:LDL modification was assessed by measuring the contents of two major molecular species of lysophosphatidylcholine (LPC) using electrospray ionization-liquid chromatography/mass spectrometry. The proinflammatory activity of the modified LDL was evaluated by determining monocyte chemoattractant protein-1 (MCP-1) mRNA expression and transcriptional factor nuclear factor-kappaB (NF-κB) activity in HUVEC.Key results:Indoxam dose-dependently inhibited palmitoyl- and stearoyl-LPC production in LDL incubated with snake venom sPLA2 (IC50 1.2 μM for palmitoyl-LPC, 0.8 μM for stearoyl-LPC). MCP-1 mRNA expression and NF-κB activity were enhanced by venom sPLA2-treated LDL, which was completely suppressed by indoxam but not by thioetheramide-PC, a competitive sPLA2 inhibitor. Indoxam also suppressed LPC production in LDL treated with human synovial type IIA sPLA2. Tumour necrosis factor α (TNFα) increased type V sPLA2 expression in HUVEC. Indoxam dose-dependently suppressed LPC production in native and glycoxidized LDL treated with TNFα-stimulated HUVEC. Indoxam suppressed MCP-1 mRNA expression and NF-κB activity in TNFα-stimulated HUVEC incubated with native or glycoxidized LDL.Conclusions and implications:Indoxam prevented sPLA2-induced LPC production in native and glycoxidized LDL as well as LDL-induced inflammatory activity in HUVEC. Our results suggest that indoxam may be a potentially useful anti-atherogenic agent.British Journal of Pharmacology (2008) 153, 1399–1408; doi:10.1038/bjp.2008.12; published online 11 February 2008 [ABSTRACT FROM AUTHOR]

In this study, we report the case of a 68-year-old man complaining of involuntary movement of his left shoulder and lower jaw plus dyspnea. On cranial computed tomography and magnetic resonance imaging, marked and symmetrical calcification at the basal ganglia and dentate nuclei was documented. An elevated cerebrospinal fluid (CSF) lactate level was confirmed by spinal tap examination and magnetic resonance spectroscopy. The raised CSF lactate level, clinical characteristics such as diabetes, bilateral hearing loss and symmetrical cerebral calcification strongly suggested some kinds of mitochondrial disease. However, gene analysis of peripheral blood leukocytes revealed no typical or known mutations. Under the diagnosis of Fahr's disease, we treated him with haloperidol, which completely abolished his symptoms. In Ellsworth–Howard test, he showed markedly decreased phosphaturic response to parathyroid hormone with same pattern as type 2 pseudohypoparathyroidism. This abnormal response in our patient, probably due to respiratory alkalosis reflecting chronic hyperventilation, might in part explain similar mechanism of ectopic calcification underlying these two diseases. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported a relationship between obesity and periodontal disease. Obesity is the strongest risk factor for type 2 diabetes, which is, in turn, a risk factor for periodontal disease. An oral glucose tolerance test is necessary to diagnose diabetes; however, no study has examined the relationship between obesity and periodontal disease by taking oral glucose tolerance test results into consideration. In all, 584 Japanese women aged between 40 and 79 years old, with at least 10 teeth, underwent health examinations. Body mass index, waist–hip ratio, body fat, and oral glucose tolerance test results were used as independent variables with known risk factors for periodontal disease. Mean probing pocket depth and mean attachment loss were used as the dependent variables. In all of the analyses, body mass index, body fat, and waist–hip ratio were significantly associated with the highest quintile of mean probing pocket depth, even when adjusted for oral glucose tolerance test results. In the multivariate analysis, the subjects with the highest quartile of body mass index had a significantly higher odds ratio (OR) for the highest quintile of mean probing pocket depth [OR, 4.3; 95% confidence interval (CI), 2.1–8.9; p < 0.001], whereas neither impaired glucose tolerance nor diabetes were significantly associated with deep pockets. The relationships between the obesity indexes and mean attachment loss did not reach statistical significance. Obesity was associated with deep pockets in Japanese women, even after adjusting for oral glucose tolerance test. [ABSTRACT FROM AUTHOR]

The stomach and the duodenum are frequent sites of involvement by diminutive lesions in Crohn's disease (CD).To assess mucosal proinflammatory cytokines and chemokines in gastroduodenal lesions of CD.13C-Urea breath test and upper endoscopy were performed in 29 CD patients and seven control subjects, and biopsy specimens were obtained from the gastric cardia and the duodenum. Histology and mucosal levels of IL-1β, IL-8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients, these procedures were repeatedly performed after administration of famotidine.H. pyloriwas less frequently positive in CD patients than in controls (10% vs. 71%,P = 0.003). Prevalence of cardial and duodenal lesion was significantly higher in CD than in controls (59% vs. 0%,P = 0.008 for gastric lesion; 45% vs. 0%,P =0.034 for duodenal lesion). There were no differences in IL-1β, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1β and IL-8 were significantly higher in positive duodenal lesion than in negative duodenal lesion. However, there were no such differences with respect to cardial lesions. Endoscopic findings remained unchanged after administration of famotidine, while there was a trend towards decreases in IL-1β and IL-8 in the gastric cardia.The pathogenesis of diminutive lesions of CD may be different between the stomach and the duodenum. Famotidine may not have a therapeutic effect on duodenal lesion in CD. [ABSTRACT FROM AUTHOR]

Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E2 (PGE2) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O2–) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O2– and PGE2 production in diabetic rats.STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O2– production, glomerular PGE2 synthesis and creatinine clearance were examined.Glomerular O2– production increased in untreated diabetic rats compared to non-diabetic controls (142.2 ± 12.4 vs. 65.4 ± 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O2– production (93.7 ± 6.7 counts/mg protein/min). Glomerular PGE2 synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE2 synthesis was reduced and creatinine clearance tended to decrease by the treatment.Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O2– production with subsequent decrease in PGE2 production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

We report on two Japanese brothers with hereditary deficiency in γ-glutamyl transpeptidase. The propositus was 48 years old when he first visited our medical center and had a 51-year-old brother. The brothers were both tall and slender and had long limbs; the younger was diagnosed as having Marfan syndrome. Both patients both showed a tendency to retarded mental development. γ-Glutamyltranspeptidase activity was below the detection limit of 1 IU/L in both patients. Glutathionaemia and glutathionuria were evident in both brothers. The analyses of sulphydryl compounds in the plasma (and serum for certain test items) and urine indicated high concentrations of glutathione, γ-glutamylcysteine, cysteine and cysteinylglycine. Urine amino acid analysis on an automatic analyser showed a slightly increased excretion of cystine and a large peak in the citrulline position due, at least in part, to thio-compounds. [ABSTRACT FROM AUTHOR]

To elucidate the relationship between glycaemic control, blood pressure and body-weight change after smoking cessation in type 2 diabetic patients. We examined HbA1c, blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control. Body weight slightly increased after quitting smoking. Although HbA1c levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 ± 0.3% before quitting smoking; 7.4 ± 0.3% 6 months after quitting smoking, p < 0.05; 7.8 ± 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 ± 3 vs. 76 ± 3 mmHg, p < 0.01). The increase in HbA1c at month 12 after quitting smoking correlated with body mass index before quitting smoking ( r = 0.72, p < 0.005) and serum triglyceride before quitting smoking ( r = 0.68, p < 0.01). Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking. [ABSTRACT FROM AUTHOR]

Summary The development of informative polymorphic markers is essential for QTL mapping. We developed 50 microsatellite markers from BAC clones containing genes that were predicted to map swine chromosome 4 (SSC4) according to comparative analysis between human and swine chromosomes, and constructed a linkage map that consisted of 37 markers including 24 markers closely linked to genes in BAC clones. Microsatellite markers were developed by direct-sequencing of BAC clones and our results demonstrated that this method was effective for developing microsatellite markers in specific regions on chromosomes. Effective development of microsatellite markers closely linked to genes can further accelerate the comparative studies of chromosomes between different species. [ABSTRACT FROM AUTHOR]

BackgroundIt remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation. ObjectiveWe compared the number and function of mast cell progenitors present in the peripheral blood from donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis accompanied by high serum IgE (IgE > 5000 U/mL). MethodsPurified peripheral blood cells were cultured in serum-free methylcellulose containing stem cell factor (SCF), IL-6 plus IL-3. Fresh methylcellulose containing the cytokines was layered over every 2 weeks. The cultured mast cells were retrieved from the methylcellulose and were functionally analysed. ResultsMast cell colonies were distinguished at 6 weeks of culture as other colony types had been degenerated. The number of mast cell colony-forming cells varied depending on donors and was not significantly increased in peripheral blood from the hyper-IgE atopic patients. A significant inversed correlation was found between the number of mast cells per one colony and the ages of donors. The cultured mast cells derived from atopic patients and those from normal IgE donors equally expressed FcεRI and released histamine through FcεRI, although IL-4 priming in vitro markedly enhanced the function of mast cells regardless of donors. ConclusionsThese results indicate that the number of circulating mast cell progenitors may be regulated by unknown individual factors unrelated to IgE levels. Mast cell function may be regulated largely by environmental factors, such as IL-4, but not determined by their progenitors' genotypes. [ABSTRACT FROM AUTHOR]

We first describe early uses of the centrifuge for deciphering physical properties and molecular organization within living cells, as well as the development and use of centrifuge microscopes for such studies. The rationale for developing a centrifuge microscope that allows high-extinction polarized light microscopy to observe dynamic fine structures in living cells is next discussed. We then describe a centrifuge polarizing microscope (CPM) that we developed for observing fine structural changes in living cells which are being exposed to up to ≈ 11 500 times earth's gravitational field (g). With the specimen housed in a rotor supported on an air spindle motor, and imaged through an external microscope illuminated by a precisely synchronized flash of less than 10 ns duration from a Nd:YAG laser, the image of the spinning object remains steady up to the maximum speed of 11 700 rev min-1, or up to ≈ 11 500 × g. The image is captured, at up to 25 frames s-1, by an interference-fringe-free CCD camera that is synchronized to the centrifuge rotor. At all speeds (in 100 rev min-1 increments), the image is resolved to better than 1 µm, while birefringence of the specimen, housed in a specially designed specimen chamber that suffers low-stress birefringence and prevents leakage of the physiological solutions, is detected with a retardance sensitivity of better than 1 nm. Differential interference contrast and fluorescence images (532 nm excitation) of the spinning specimen can also be generated with the CPM. The second part of this study (Inoué et al., J. Microsc. 201 (2001) 357–367, describes several biological applications of the CPM that we have explored. Individual live cells, such as oocytes and blood cells, are supported on a sucrose or Percoll density gradient while other cells, such as cultured fibroblasts and Dictyostelium amoebae, are observed crawling on glass surfaces. Observations of these cells exposed to the high G fields (centripetal acceleration/g) in the CPM are yielding many new results that lead to intriguing questions regarding the organization and function of fine structures in living cells and related quasi-fluid systems. [ABSTRACT FROM AUTHOR]

Summary A porcine bacterial artificial chromosome (BAC) library consisting of 103 488 clones has been constructed. The average insert size in the BAC vector was calculated to be 133 kb based on the examination of 189 randomly selected clones, indicating that the library contained 4.4 genome equivalents. The library can be screened by two-step PCR. The first screening step is performed on 22 superpools, each containing 4704 clones (49×96 well plates). In the second screening step, 49 plates comprising a superpool are arrayed in a 7×7 matrix and 4D-PCR is performed. Screening of the library superpools by PCR for 125 marker sequences selected from different regions of swine genome revealed 123 sequences, indicating that the library is not biased. Subsequent screenings (4D-PCR) were successfully applied for identification of clones containing each marker sequence. This porcine BAC library and the PCR screening system are useful for isolation of genomic DNA fragments containing desired sequences. [ABSTRACT FROM AUTHOR]

The article discusses the case of 64-year-old schizophrenic man with acute abdominal pain. A computed tomography (CT) scan confirmed massive hepatic portal venous gas, an uncommon feature of acute abdomen with a high mortality rate, and pneumatosis intestinalis. It was believed that the massive hepatic portal venous gas was caused by glycerol enema which was given to the patient when he was quite constipated and had impressive amounts of stool in his colon.

The article presents a medical study about the inflammatory granulation polyps of the colon. The most common types of inflammatory polyps are pseudopolyps that can be found in patients with ulcerative colitis and Crohn's disease. The development of inflammatory polyps are visible in the prolapse of the rectum or rectosigmoid junction. There are rare inflammatory polyps which include inflammatory fibroid polyps, inflammatory myoglandular polyps and pyogenic granulomas.

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

A profound developmental experience is the emergence of adolescent romantic relationships and first feelings of love. However, the daily nature of feeling loved in adolescents' everyday lives is poorly understood. We investigated how daily stress severity was associated with adolescents' levels of feeling loved and whether romantic partner support moderated these associations. Furthermore, we investigated this for non-interpersonal and interpersonal stressors. N = 97 mixed-gender adolescent romantic couples (age M = 16.38, SD = 1.02) from an ethnically diverse sample (42.2% Hispanic/Latino/a/x, 44.7% White) participated in dyadic diary assessments twice a week for 12 consecutive weeks. Both partners independently completed open-ended questions about a daily stressor, indicating stress severity, perceived partner support, and feeling loved. Daily stressors were coded for non-interpersonal and various types of interpersonal stressors. Results from the dyadic multilevel model showed that days with lower than average support from a romantic partner amplify the adverse effects of stress severity on feeling loved, especially when the partner is involved in the stressor. We discuss the spillover of stress in romantic relationships and the stress-buffering functions of adolescent romantic partner support. Adolescent romantic partners are potentially essential regulators of stress, increasing adolescents' feelings of love. RESEARCH HIGHLIGHTS: Romantic love is central in adolescents' lives; we showed that adolescents generally feel loved by romantic partners. Feeling loved fluctuates daily as adolescents feel less loved on stressful days. However, when adolescents perceive their partner as supportive, there is no association between stress and feeling loved. Partner support is protective for feeling loved. The current study provides essential insights into when adolescents and why adolescents feel loved., (© 2024 John Wiley & Sons Ltd.)

We describe a successful surgical technique of abdominal trachelectomy and re-vaginoplasty for cervico-vaginal stenosis following unsuccessful uterovaginal anastomosis and vaginoplasty in a patient with congenital cervical and vaginal aplasia. After the surgical procedure, cervico-vaginal stenosis was resolved and periodic menstruation without dysmenorrhoea resumed. While long-term follow-up is essential to ensure successful pregnancy and delivery, we conclude that this novel surgical procedure is a promising alternative for improvement of the quality of life and normal sexual function, and for preservation of fertility in patients with cervical and vaginal aplasia., (© 2021 John Wiley & Sons Ltd.)

Following exposure to drugs of abuse, long-term neuroadaptations underlie persistent risk to relapse. Endocannabinoid signaling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate endocannabinoid biosynthesis and metabolism in regulating relapse behaviors following prolonged periods of drug abstinence has not been examined. Here, we investigated how pharmacological manipulation of lipases involved in regulating the expression of the endocannabinoid 2-AG in the nucleus accumbens (NAc) influence cocaine relapse via discrete neuroadaptations. At prolonged abstinence (30 days) from cocaine self-administration, there is an increase in the NAc levels of diacylglycerol lipase (DAGL), the enzyme responsible for the synthesis of the endocannabinoid 2-AG, along with decreased levels of monoacylglycerol lipase (MAGL), which hydrolyzes 2-AG. Since endocannabinoid-mediated behavioral plasticity involves phosphatase dysregulation, we examined the phosphatase calcineurin after 30 days of abstinence and found decreased expression in the NAc, which we demonstrate is regulated through the transcription factor EGR1. Intra-NAc pharmacological manipulation of DAGL and MAGL with inhibitors DO-34 and URB-602, respectively, bidirectionally regulated cue-induced cocaine seeking and altered the phosphostatus of translational initiation factor, eIF2α. Finally, we found that cocaine seeking 30 days after abstinence leads to decreased phosphorylation of eIF2α and reduced expression of its downstream target NPAS4, a protein involved in experience-dependent neuronal plasticity. Together, our findings demonstrate that lipases that regulate 2-AG expression influence transcriptional and translational changes in the NAc related to drug relapse vulnerability., (© 2021 Society for the Study of Addiction.)

Hair graying is a representative sign of aging in animals and humans. However, the mechanism for hair graying with aging remains largely unknown. In this study, we found that the microscopic appearance of hair follicles without melanocyte stem cells (MSCs) and descendant melanocytes as well as macroscopic appearances of hair graying in RET-transgenic mice carrying RET oncogene (RET-mice) are in accordance with previously reported results for hair graying in humans. Therefore, RET-mice could be a novel model mouse line for age-related hair graying. We further showed hair graying with aging in RET-mice associated with RET-mediated acceleration of hair cycles, increase of senescent follicular keratinocyte stem cells (KSCs), and decreased expression levels of endothelin-1 (ET-1) in bulges, decreased endothelin receptor B (Ednrb) expression in MSCs, resulting in a decreased number of follicular MSCs. We then showed that hair graying in RET-mice was accelerated by congenitally decreased Ednrb expression in MSCs in heterozygously Ednrb-deleted RET-mice [Ednrb(+/-);RET-mice]. We finally partially confirmed common mechanisms of hair graying with aging in mice and humans. Taken together, our results suggest that age-related dysfunction between ET-1 in follicular KSCs and endothelin receptor B (Ednrb) in follicular MSCs via cumulative hair cycles is correlated with hair graying with aging., (© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine-mediated neuromuscular disease caused by a CAG repeat expansion in the androgen receptor ( AR ) gene. While transcriptional dysregulation is known to play a critical role in the pathogenesis of SBMA, the underlying molecular pathomechanisms remain unclear. DNA methylation is a fundamental epigenetic modification that silences the transcription of various genes that have a CpG-rich promoter. Here, we showed that DNA methyltransferase 1 (Dnmt1) is highly expressed in the spinal motor neurons of an SBMA mouse model and in patients with SBMA. Both genetic Dnmt1 depletion and treatment with RG108, a DNA methylation inhibitor, ameliorated the viability of SBMA model cells. Furthermore, a continuous intracerebroventricular injection of RG108 mitigated the phenotype of SBMA mice. DNA methylation array analysis identified hairy and enhancer of split 5 ( Hes5 ) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. Moreover, Hes5 over-expression rescued the SBMA cells possibly by inducing Smad2 phosphorylation. Our findings suggest DNA hyper-methylation underlies the neurodegeneration in SBMA., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16(Ink4a) . Therefore, dysregulation of the Bmi-1/p16(Ink4a) pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16(Ink4a) pathway occurs during aging in vivo. Using real-time in vivo imaging of p16(Ink4a) expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16(Ink4a) pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16(Ink4a) expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective: Various methods have been reported for the detection of unknown primaries in cervical lymph node metastasis. Recently, we applied new optical devices and modifications of endoscopic techniques for the detection of primary lesions, and obtained excellent results. The detection rate of the new method was compared with that of previous methods., Study Design: Retrospective., Methods: A total of 51 patients with cervical lymph node metastasis from an unknown primary site (CUP) were referred to our hospital between January 2000 and May 2009, and were retrospectively analyzed. Between 2000 and 2005, the observation by normal video-endoscope in straight head position was performed to detect the primary lesions in the outpatient setting. Since 2006, a new method for detection of primary lesions has been employed. The method includes the use of new optical devices (hooded video-endoscope and narrow-band imaging endoscope) and different head positions (head torsion technique, Valsalva maneuver, and the Killian position)., Results: The detection rate of primary lesions using the new method was 71% (15 of 21), which was better than the 30% (10 of 30) obtained with the conventional method. All primary lesions identified using the new method were located in the hypopharynx., Conclusions: The new method was able to detect primary lesions in 71% of cases with CUP. The higher rate achieved with the new method was probably due to the clear visualization of the hypopharynx. Thus, the new method was shown to be useful for the detection of primary lesions in cases of CUP.