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Takeshi Osonoi, Miyoko Saito, Naoya Koda, Satako Douguchi, Takako Nakano, Kensuke Ofuchi, Makoto Katoh Naka Kinen Clinic, Ibaraki, JapanCorrespondence: Makoto KatohNaka Kinen Clinic, 745-5 Nakadai, Naka-Shi, Ibaraki 311-0113, JapanTel +81-29-353-2800Fax +81-29-295-5400Email m-katou@kensei-kai.comPurpose: We retrospectively evaluated the long-term effect of dipeptidyl peptidase (DPP)-4 inhibitors on estimated glomerular filtration rate (eGFR) slopes, and then evaluated the beneficial interaction between DPP-4 inhibitor initiation and baseline use of α-glucosidase inhibitor and/or metformin in patients with diabetic kidney disease.Patients and Methods: Altogether, 1512 patients with type 2 diabetes were receiving DPP-4 inhibitor therapy over 1 year and were followed up for a maximum of 2 years before and after 7 years of treatment. The decline in renal function was estimated as the slope of the individual linear regression line of eGFR over 2-year follow-up. Prescription data on medications before and after DPP-4 inhibitor treatment were examined.Results: The mean length of DPP-4 inhibitor treatment was 5.3 ± 2.6 years. The baseline mean eGFR slope (mL/min/1.73m2/year) was − 2.24 ± 6.05. After DPP-4 inhibitor treatment, mean eGFR slope was significantly improved (− 1.53 ± 6.36, P < 0.01) in patients with type 2 diabetes. This effect appeared more pronounced for baseline use of α-glucosidase inhibitor and/or metformin in patients with diabetic kidney disease. These non-users showed a trend towards attenuation or no effects.Conclusion: In the present study, patients treated with DPP-4 inhibitors had a significantly slower annual loss of kidney function. The benefit appears pronounced in α-glucosidase inhibitor and metformin users with advanced renal dysfunction. These results suggest that the beneficial effects of DPP-4 inhibitors on kidney function may have occurred in the presence of an α-glucosidase inhibitor and/or metformin.Keywords: DPP-4 inhibitor, α-glucosidase inhibitor, metformin, eGFR slope, type 2 diabetes

The degree of acceptance of dog guides at public facilities, which is required by law in Japan, was investigated, and evidence of rejection was found. Japanese people with visual impairments who used dog guides reported higher daily stress levels than did those who did not use dog guides. [ABSTRACT FROM AUTHOR]

Unlabelled: We report the case of a male patient with infantile hypophosphatasia associated with severe hypercalcaemia and mild respiratory insufficiency. At the age of 2 months, severe hypercalcaemia, low levels of serum alkaline phosphatase activity, and elevated urinary excretion of calcium and phosphoethanolamine were noted. Radiological findings showed generalized osteopenia and disturbed and irregular ossification of the metaphyses. Their involvement had spontaneously improved at the age of 6 months. A genetic study revealed that the tissue-nonspecific alkaline phosphatase gene of the patient had two novel mutations, K207E and G409C, derived from the mother and father, respectively. A reconsitution experiment revealed that both mutant gene products had low but significant enzymatic activity.Conclusion: The detection of tissue-nonspecific alkaline phosphatase gene mutations and expression studies to determine the enzymatic activity of mutant gene products was useful for assessing the clinical course of this patient with hypophosphatasia. [ABSTRACT FROM AUTHOR]

Urban parks are essential for community revitalization; for example, they are places to walk dogs and interact with other dog keepers. This study focused on an urban park with a dog-friendly area to be used by both dog keepers and other users as an alternative to off-leash dog parks that completely separate them and clarified aspects of park use through behavioral observation. The behaviors of 7122 visitors in 14 areas in the park and 294 pairs of dogs and their keepers in the dog-friendly area were observed. The results showed that the visitors' age groups and use behaviors differed by area. The dog-friendly area was in constant demand among dog keepers as a place where they could stay and interact with others and as a destination or relay point when walking their dogs. Visitors used the park in accordance with rules and morals, and the park was well managed. As it can be comfortably used by everyone (with or without dogs), this park can serve as a model for the development and maintenance of community-based multifunctional parks in urban areas., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fetal organs and organoids are important tools for studying organ development. Recently, porcine organs have garnered attention as potential organs for xenotransplantation because of their high degree of similarity to human organs. However, to meet the prompt demand for porcine fetal organs by patients and researchers, effective methods for producing, retrieving, and cryopreserving pig fetuses are indispensable. Therefore, in this study, to collect fetuses for kidney extraction, we employed cesarean sections to preserve the survival and fertility of the mother pig and a method for storing fetal kidneys by long-term cryopreservation. Subsequently, we evaluated the utility of these two methods. We confirmed that the kidneys of pig fetuses retrieved by cesarean section that were cryopreserved for an extended period could resume renal growth when grafted into mice and were capable of forming renal organoids. These results demonstrate the usefulness of long-term cryopreserved fetal pig organs and strongly suggest the effectiveness of our comprehensive system of pig fetus retrieval and fetal organ preservation, thereby highlighting its potential as an accelerator of xenotransplantation research and clinical innovation.

Human pluripotent stem cells have been employed in generating organoids, yet their immaturity compared to fetal organs and the limited induction of all constituent cell types remain challenges. Porcine fetal progenitor cells have emerged as promising candidates for co-culturing with human progenitor cells in regeneration and xenotransplantation research. This study focused on identifying proper preservation methods for porcine fetal kidneys, hearts, and livers, aiming to optimize their potential as cell sources. Extracted from fetal microminiature pigs, these organs were dissociated before and after cryopreservation-thawing, with subsequent cell quality evaluations. Kidney cells, dissociated and aggregated after vitrification in a whole-organ form, were successfully differentiated into glomeruli and tubules in vivo. In contrast, freezing hearts and livers before dissociation yielded suboptimal results. Heart cells, frozen after dissociation, exhibited pulsating heart muscle cells similar to non-frozen hearts. As for liver cells, we developed a direct tissue perfusion technique and successfully obtained highly viable liver parenchymal cells. Freezing dissociated liver cells, although inferior to their non-frozen counterparts, maintained the ability for colony formation. The findings of this study provide valuable insights into suitable preservation methods for porcine fetal cells from kidneys, hearts, and livers, contributing to the advancement of regeneration and xenotransplantation research.

A 35-year-old woman pregnant with twins developed nephrotic syndrome (NS) at 33 weeks' gestation, but her blood pressure remained within the normal range throughout gestation and puerperium. At 34 weeks' gestation, she delivered healthy twins via Caesarean section. After delivery, she developed massive proteinuria (21.1 g/day) and severe hypoalbuminemia (1.0 g/dL). A renal biopsy performed 19 days after delivery revealed IgA nephropathy (IgAN) and preeclampsia. She was treated with steroids, and the NS gradually resolved. This is a rare case of massive gestational proteinuria with IgAN and preeclampsia pathologically that did not meet the clinical criteria for preeclampsia.

A variety of naphthalenediolates were orthogonally introduced to the boron unit of dipyrrolyldiketone boron complexes, exhibiting electronic properties that depended on the substituting positions of the naphthyl moieties. Combining the anion complexes with countercations resulted in the formation of ion-pairing assemblies with supporting stacking interactions of the naphthyl units.

Purpose: To systematically review the effects of surgeon fatigue on postoperative mortality and postoperative complications after elective and non-elective surgeries., Methods: A database search was conducted for original articles published in PubMed between 2000 and 2020 with the keywords: "surgeon," "sleep deprivation," "sleep deprived," "fatigued," "mortality," "morbidity," and "outcomes." We selected articles that disclosed actual numbers of patients who underwent surgery by fatigued or rested surgeons, rates of postoperative mortality, or total postoperative complications., Results: Of the 1427 articles identified, 16 met the selection criteria and were included. Eight of the 16 also included total postoperative complications. Analysis revealed no significant differences in the rates of postoperative mortality after elective and non-elective surgeries or total postoperative complications of elective surgeries or non-elective surgeries performed by fatigued vs. rested surgeons. The relative risks were 1.03 [95% confidence interval (CI), 0.86-1.24], 1.08 (95% CI, 0.85-1.38), 0.99 (95% CI, 0.95-1.04), and 0.93 (95% CI, 0.67-1.28), respectively., Conclusion: Surgeon fatigue does not affect the rates of postoperative mortality or total postoperative complications after elective surgeries and may have little to no effect on the rates of postoperative mortality or total postoperative complications after non-elective surgeries.

In order to clarify the ability of animals to communicate with humans, it is necessary to examine the behaviors of animals directed at humans, taking into account individual differences. This study investigated whether the behaviors of goats ( Capra hircus ) can be predicted when given an unsolvable task. Two experiments were performed in a paddock using 16 domesticated goats. In Experiment 1, behavioral tests were conducted to determine the goats' social rank and reactivity toward a stranger. In Experiment 2, the goats' behaviors in an unsolvable task and two control conditions in which either only a human or bucket was presented were examined. The behaviors of the goats were video-recorded and compared between the conditions. Then, we examined whether the behaviors of goats in the presence of both the human and unsolvable task can be predicted from the scores for social rank and reactivity toward humans. Compared with the control conditions, the goats increased physical contact with the human, but did not increase gazing. It is possible that differences in individual characteristics and long-term experiences with humans can lead to differences in human-directed behaviors of animals. Although the social rank order of the goats was clearly linear, there was no correlation between their behaviors in the unsolvable task and their social rank. The goats that tended to interact with the stranger in Experiment 1 were more likely to approach and establish contact with the human in the unsolvable task than goats that reacted more averse toward humans. There was no association between the level of reactivity toward the stranger and the goats' involvements in the unsolvable task. Therefore, it is possible that the goats which increased interactions with humans did not necessarily have low motivation to engage in unsolvable tasks, but relied on humans as a means of communication. In conclusion, the behavioral changes and its diversity as the responses toward short-term changes in the environment, such as the presence or absence of humans and unsolvable tasks, were related to differences in individual behavioral characteristics (i.e., reactivity toward humans)., (Copyright © 2020 Yoshida and Koda.)

Background: Ablation of the pulmonary venous carina is occasionally required for pulmonary vein isolation (PVI) despite its nonessential role in ipsilateral PVI from the anatomical (endocardial) viewpoint. Although the Bachmann bundle (BB) is a common and main interatrial band, local variations in small tongues of muscular fibers were frequently found in autopsy studies., Objective: We sought to clarify the effect of the electrical conduction pattern from the right atrium (RA) to the left atrium (LA) during sinus rhythm on the necessity of performing right-sided pulmonary venous carina ablation to achieve PVI., Methods: Study subjects comprised 37 consecutive patients undergoing initial catheter ablation of lone atrial fibrillation. During sinus rhythm, RA and LA activation maps were acquired using an electroanatomical mapping system. LA breakthroughs were classified into 3 sites: BB, fossa ovalis (FO), and right-sided pulmonary venous carina. Patients were divided into the carina-ABL (ablation) or non-carina-ABL group on the basis of the necessity of pulmonary venous carina ablation to achieve PVI., Results: Patients were classified in the non-carina-ABL group (n = 26 [70%]) and carina-ABL group (n = 8 [22%]) after excluding 3 patients (8%) because of their complex ablation lesion sets. Breakthrough occurred in the BB (n = 21 patients [62%]), FO (n = 7 [21%]), carina (n = 1 [3%]), carina and BB (n = 3 [9%]), and carina and FO (n = 2 [6%]). Carina breakthrough occurred in 6 patients (75%) in the carina-ABL group but in no patients in the non-carina-ABL group (P < .0001)., Conclusion: PVI was not achievable without carina ablation in one-fifth of patients, probably because of epicardial connections present between the right-sided pulmonary venous carina and the RA., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Recently, studies in the United States and European countries have shown that the degree of attachment is associated with the attribution of emotions to companion animals. These studies imply that investigating the degree of attachment to companion animals is a good way for researchers to explore animal emotions and then improve animal welfare. Although a promising area of study, in Japan, no empirical studies have examined the correlation between the degree of attachment and the attribution of emotions to companion animals. In this research, we aimed to assess companion animal owners' attribution of six primary (anger, joy, sadness, disgust, fear and surprise) and four secondary (shame, jealousy, disappointment and compassion) emotions to their dogs and cats, as well as how the degree of attachment related to such attribution of emotions from a Japanese cultural perspective. The "Pet Bonding Scale" (PBS), which is used to determine the level of bonding between humans and animals, was introduced to measure respondents' degree of attachment to their companion animals. The results of a questionnaire (N = 546) distributed throughout Japan showed that respondents attributed a wide range of emotions to their animals. Companion animals' primary emotions, compared to secondary emotions, were more commonly attributed by their owners. The attribution of compassion and jealousy was reported at a high level (73.1% and 56.2%, respectively), which was surprising as compassion and jealousy are generally defined as secondary emotions. All participants were highly attached to their companion animals, and this attachment was positively associated with the attribution of emotions (9/10) to companion animals (all p < 0.05). This study is one of the first to investigate animal emotions by analyzing the bonding between companion animals and owners in Japan, and it can therefore provide knowledge to increase Japanese people's awareness of animal welfare.

Introduction: The superior vena cava (SVC) is a main source of nonpulmonary vein (PV) ectopies initiating atrial fibrillation (AF). Empiric SVC isolation may improve rhythm outcomes after catheter ablation of AF. Because the SVC passes immediately adjacent to the right superior PV (RSPV), an electrophysiological relation could be present between the two structures. The present study aimed to estimate the interrelation between the SVC and RSPV by evaluating arrhythmogenic activities observed during catheter ablation of AF., Methods and Results: Study subjects comprised 121 consecutive patients referred for catheter ablation of paroxysmal AF. Isoproterenol infusion was used to induce ectopies and AF. Patients were divided into two groups depending on the presence of arrhythmogenic SVC: arrhythmogenic-SVC (A-SVC) and nonarrhythmogenic SVC (Non-A-SVC) groups. The prevalence of females was higher and body surface area was smaller in the A-SVC group (N = 22) than Non-A-SVC group (N = 99). Arrhythmogenic activities were observed in 60 (49%) RSPVs, 24 (20%) right inferior PVs, 72 (59%) left superior PVs, and 31 (25%) left inferior PVs. Arrhythmogenic RSPVs were more prevalent in the A-SVC group than Non-A-SVC group (86% vs. 41%, P = 0.0001), whereas these prevalences in the other three PVs were not different between groups (P >0.3). In multivariable analysis, arrhythmogenic RSPV was the only independent predictor of arrhythmogenicity of the SVC (OR, 8.53; 95% CI 2.31-31.46; P = 0.001)., Conclusions: An electrophysiological interrelation may be present between the SVC and RSPV in patients with paroxysmal AF. Semiempiric SVC isolation limited to patients with an arrhythmogenic RSPV may be a more efficient treatment strategy., (© 2017 Wiley Periodicals, Inc.)

The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well known. We report that mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and expression remained at similar levels at 12 months. In Mkx -/- mice, age-dependent expansion of the PDL at the maxillary first molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx -/- mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx +/+ mice. PDL cells lost their shape in Mkx -/- mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx -/- PDL revealed an increase in osteogenic gene expression and no change in PDL- and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkx-overexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis., (© 2017. Published by The Company of Biologists Ltd.)

Many Japanese elementary schools keep small animals for educational purposes, and the effects and challenges have been investigated. Although goats are medium-sized animals that are familiar to Japanese, few practical studies have been conducted on keeping goats in schools. This study investigated the effects and challenges of keeping goats in elementary schools and discussed its educational possibilities. A semi-structured interview survey was conducted with 11 personnel that were responsible for keeping goats in 6 elementary schools in urban areas. They described benefits, problems, and tips related to keeping goats. Participant observation was also conducted on daily human-goat interactions in these schools. The results indicated that children in all six grades were able to care for goats. Goats were used for various school subjects and activities. As a result of keeping goats, children developed affection for them, attitude of respect for living things, greater sense of responsibility, and enhanced interpersonal interactional skills. Stronger ties between the schools and parents and community were developed through cooperation in goat-keeping. Some anxieties existed about the risk of injury to children when interacting with goats. Other challenges included the burden of taking care of the goats on holidays and insufficient knowledge about treatment in case of their illness or injury. The results suggested similarities to the benefits and challenges associated with keeping small animals in elementary schools, although the responsibility and the burden on the schools were greater for keeping goats than small animals because of their larger size and the need for children to consider the goats' inner state and to cooperate with others when providing care. At the same time, goats greatly stimulated interest, cooperation, and empathy in children. Goats can expand educational opportunities and bring about many positive effects on child development.

Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)(-/-) rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx(-/-) mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx(-/-) mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx(-/-) TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx(+/+) TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY-box (Sox)5, Sox6, and Sox9 Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering.

Objective: Plasma norepinephrine (NE) level can be a guide to mortality in patients with heart failure. This study aimed to evaluate the significance of plasma NE level compared with plasma natriuretic peptides (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) levels in patients with atrial fibrillation (AF)., Methods: Included in this study were 137 consecutive patients referred for catheter ablation of lone AF (paroxysmal in 90 and persistent in 47 patients). Blood samples for measurements of ANP, BNP and NE were drawn in the supine position before the procedure., Results: ANP, BNP and NE levels were greater in patients with persistent AF than in patients with paroxysmal AF (median (25th-75th centile)=28 (18-49) vs 69 (36-106), p<0.0001; 28 (15-50) vs 94 (39-156), p<0.0001; and 315 (223-502) vs 382 (299-517) pg/mL, p=0.04, respectively). NE level correlated weakly with ANP and BNP levels (r=0.28 and r=0.23, respectively, p<0.01 for both). BNP and NE levels differed between patients with and without recurrence of AF (55 (26-135) vs 35 (18-64), p=0.005 and 431 (323-560) vs 302 (225-436) pg/mL, p<0.001, respectively). Of note, only NE level was significantly greater in patients with symptomatic sick sinus syndrome (SSS) (n=21) than in those without SSS (560 (466-632) vs 321 (242-437) pg/mL, p<0.0001). Logistic regression analysis showed NE level to be the only independent discriminator for SSS (OR 1.006, 95% CI 1.002 to 1.010, p=0.001)., Conclusions: An increase in plasma NE level was observed in patients with AF and SSS. Although this implies a pathophysiological link between clinical manifestation of SSS and the autonomic nervous dysfunction, further studies are needed to clarify the mechanisms for this novel finding., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Although radiofrequency ablation creates myocardial necrosis leading to troponin T (TnT) release into the systemic circulation, the significance of TnT elevation after atrial fibrillation (AF) ablation is unknown., Objective: To demonstrate a possible mechanism of reverse structural remodeling in the left atrium (LA) by evaluating postprocedural TnT elevation., Methods: This study included 106 patients with an enlarged LA (paroxysmal AF, n = 43; persistent AF, n = 63). All patients underwent pulmonary vein isolation alone in the index procedure. Left atrial volume indexed to body surface area (LAVi) was measured by echocardiography before ablation and 6 months after sinus rhythm restoration. Patients were divided into responders (n = 53) and nonresponders (n = 53) based on a cutoff value of 23% reduction in LAVi. The TnT level was measured 12 hours postprocedure., Results: LAVi decreased from 43 ± 13 to 33 ± 12 mL/m(2) (P < .0001). The TnT level was higher in responders than in nonresponders (1.31 ± 0.34 μg/L vs 0.88 ± 0.29 μg/L; P < .0001) and correlated linearly with percent reduction in LAVi (R = .54; P < .0001). Also in multivariate analysis, the TnT level was the only independent predictor for responders (odds ratio 90.1; 95% confidence interval 14.95-543.3; P < .0001). The TnT level in patients who required a repeat procedure (n = 30) was lower than that in patients who did not require a repeat procedure only in the persistent AF group (0.92 ± 0.38 μg/L vs 1.16 ± 0.37 μg/L; P = .01)., Conclusion: Greater elevation of the TnT level was related both to favorable outcomes after ablation and to greater reversal of structural remodeling. Postprocedural TnT level may be reflective of the preservation of healthy LA myocardium., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

In a Medical Support Center (MSC), nurses care for both inpatients and outpatients. For outpatients receiving chemotherapy, nursing support is ended at PS1 or PS0. We also clarified the roles of MSC nurses and the timing for resuming nursing support for outpatients. We found that support was resumed between 53 and 153 days after support was first administered. By considering the services provided at the first instance of support, MSC nurses were able to build a system of medical and nursing care that the patients and their families desired.

The Medical Support Center(MSC)of the A university hospital encourages inpatients to leave the hospital and outpatients to live better at home. The medical social workers and the nurses cooperate to achieve these aims. The role of the nurses at the Medical Support Center is to collect information regarding the medical services and the welfare systems, and to provide the patients and their families with this information. We also educate the hospital staff to better understand the lives of the patients who leave hospital. We also provide cancer patients with information regarding the medical treatment available in the area, social welfare services, hospices, and palliative care, such that they can choose the method of treatment and an appropriate place to live.

Mutations of DSS (dosage sensitive sex reversal)-AHC critical region on the X chromosome, gene 1 DAX-1(NROB1)] results in X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Here we report four Japanese patients with AHC and HHG caused by the mutations of the DAX-1 gene. All patients manifested adrenal crisis at early childhood. Three patients did not show any pubertal sign and were diagnosed as having HHG. One patient manifested spontaneous pubertal development at 17 years of age. Nevertheless, his puberty did not develop further and his gonadotropin and testosterone levels decreased thereafter. Therefore, he was also diagnosed as having HHG. We performed testicular biopsy in another patient with HHG. Histological examination demonstrated Sertoli cell hypoplasia and no sperm formation in the seminiferous tubules. Molecular analysis demonstrated two novel point mutations (V269D and L278R) in two patients. Transient transfection assays showed that all these mutations (V269D, L271X, L278R, and Q395X) abolished the repression activity to both StAR and LHbeta gene promoter activation. In conclusion, we reported patients with AHC and HHG caused by the loss of function mutations of the DAX-1 gene.