Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

The significance of local government in disaster management for international migrants: the case of Minoh City, Osaka Prefecture.

Disaster research predominantly focuses on citizens, not on migrants. This tilted spotlight needs to be readjusted, since many advanced countries around the world have become immigration countries, and safeguarding the lives of migrants at times of disaster has become an important and immediate policy issue. Hence, this research concentrates on disaster management to protect the lives of migrants in a disaster-prone and de facto immigration country. The particular country and event in question are Japan and the northern Osaka earthquake of June 2018. More than 100 migrants who lived near the earthquake's epicentre rushed to an evacuation shelter managed by the local municipal government of Minoh City, Osaka Prefecture. While non-governmental organisations attract more attention, this paper centres on a local government and demonstrates the key role that it can play in both bridging and building networks across different communities, and thus in safeguarding the lives of migrants at times of disaster.

Two Siblings with Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome 4 and a Novel Variant of ATP8A2.

Cerebellar ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4) is early onset neuromotor disorder and intellectual disabilities caused by variants of ATP8A2. We report sibling cases and systematically analyze previous literature to increase our understanding of CAMRQ4. Japanese siblings presented with athetotic movements at 1 and 2 months of age. They also had ptosis, ophthalmoplegia, feeding difficulty, hypotonia, and severely delayed development. One patient had retinal degeneration and optic atrophy. Flattening of the auditory brainstem responses and areflexia developed. At the last follow-up, neither patient could sit or achieve head control, although some nonverbal communication was preserved. Whole exome sequencing revealed compound heterozygous variants of ATP8A2: NM_016529.6:c.[1741C>T];[2158C>T] p.[(Arg581*)];[(Arg720*)]. The p.(Arg581*) variant has been reported, while the variant p.(Arg720*) was novel. The symptoms did not progress in the early period of development, which makes it difficult to distinguish from dyskinetic cerebral palsy, particularly in solitary cases. However, visual and hearing impairments associated with involuntary movements and severe developmental delay may be a clue to suspect CAMRQ4.

Randomized double-blind placebo-controlled trial of hydrogen inhalation for Parkinson's disease: a pilot study.

BACKGROUND: Oxidative stress is involved in the progression of Parkinson's disease (PD). Recent studies have confirmed that molecular hydrogen (H2) functions as a highly effective antioxidant in animal models of PD. A placebo-controlled, randomized, double-blind, parallel-group clinical pilot study was conducted to assess the efficacy of hydrogen gas inhalation in Japanese patients with PD on treatment with levodopa. METHODS: Twenty participants fulfilling the Movement Disorder Society criteria were enrolled. Participants inhaled 6.5 (0.1) vol% hydrogen gas in 2 L/min of mixed air or placebo air for 16 weeks, twice a day for 1 h. RESULTS: Five participants were excluded due to deviation from the protocol of the total duration of inhalation < 112 h. No significant differences were seen in the change in the total Movement Disorder Society Unified Parkinson's Disease Rating Scale score from baseline to the 16th week between the group that inhaled hydrogen gas and the group that inhaled placebo air (Mann-Whitney U test, p > 0.05). No adverse events were seen. The compliance to the protocol-based duration of inhalation time in all participants decreased with the elderly participants, the higher daily dose of levodopa, and the higher PDQ-39 items on emotions (n = 20, p < 0.05). CONCLUSION: This pilot study revealed that the inhalation of molecular hydrogen gas was safe, but did not show any beneficial effects in patients with PD. TRIAL REGISTRATION: UMIN ID: 000,039,217 (October 6, 2018).

Recurrent de novo MAPK8IP3 variants cause neurological phenotypes.

c-Jun-amino-terminal kinase-interacting protein 3 (JIP3), encoded by MAPK8IP3, is an adaptor protein of the kinesin-1 complex and essential for axonal transport in neurons. However, an association between MAPK8IP3 variants and human disease has not been established. We identified 5 individuals from four families with recurrent de novo variants c.1732C>T (p.Arg578Cys) and c.3436C>T (p.Arg1146Cys) in MAPK8IP3. The core phenotype includes spastic diplegia, intellectual disability, cerebral atrophy, and corpus callosum hypoplasia. Zebrafish embryos overexpressing human mutant JIP3 showed axon varicosities of the posterior lateral line nerve, suggesting an adverse effect on the developing axons. Our results suggest that MAPK8IP3 variants cause a neurodevelopmental disease. ANN NEUROL 2019;85:927-933.

Identification and Characterization of Circulating Tumor Cells in Men Who have Undergone Prostatectomy for Clinically Localized, High Risk Prostate Cancer.

PURPOSE: Approximately 15% of men with newly diagnosed prostate cancer have high risk features which increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence and change surveillance and adjuvant treatment paradigms. Circulating tumor cells are thought to represent the earliest form of metastases. However, their role as biomarkers in men with high risk, localized prostate cancer is not well defined. MATERIALS AND METHODS: Two to 5 months after prostatectomy we obtained blood samples from 37 patients with high risk, localized prostate cancer, defined as stage T3a or higher, Gleason score 8 or greater, or prostate specific antigen 20 ng/ml or greater. Circulating tumor cells were enumerated using a commercial platform. Matched tumor and single circulating tumor cell sequencing was performed. RESULTS: Circulating tumor cells were detected in 30 of 37 samples (81.1%) with a median of 2.4 circulating tumor cells per ml (range 0 to 22.9). Patients with detectable circulating tumor cells showed a trend toward shorter recurrence time (p=0.12). All patients with biochemical recurrence had detectable circulating tumor cells. Androgen receptor over expression was detected in 7 of 37 patients (18.9%). Patients with biochemical recurrence had more circulating tumor cell copy number aberrations (p=0.027). Matched tumor tissue and single circulating tumor cell sequencing revealed heterogeneity. CONCLUSIONS: We noted a high incidence of circulating tumor cell detection after radical prostatectomy and shorter time to biochemical recurrence in men with a higher circulating tumor cell burden and more circulating tumor cell copy number aberrations. Genomic alterations consistent with established copy number aberrations in prostate cancer were detectable in circulating tumor cells but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts early circulating tumor cell detection could be an informative biomarker to assist with adjuvant treatment decisions.

Severity scales of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) are one type of food allergy found in neonates and infants. Few reports have defined the severity of non-IgE-GI-FAs in these populations. METHODS: Grading scales of the severity of non-IgE-GI-FAs according to extra-GI symptoms, such as poor weight gain, as well as systemic symptoms, including fever and shock, were developed and retrospectively applied to patients with non-IgE-GI-FAs. The relationship between the severity of non-IgE-GI-FAs and both clinical and laboratory findings were examined. RESULTS: Elevation of C-reactive protein levels and a decrease in total protein and albumin were observed in accordance with allergy severity. In an endoscopic examination, inflammatory findings were confirmed in large areas of the colonic mucosa in case of higher severity levels, and infiltration of inflammatory cells other than eosinophils was found in the severest grade. Extensively hydrolyzed milk or amino acid-based milk was required for all patients with the severest grade. In addition, the timing of acquiring tolerance tended to be late for this grade. CONCLUSIONS: Classification and determination of the severity of non-IgE-GI-FAs in neonates and infants may not only contribute to elucidation of the pathogenesis but may also be useful in the clinical setting.

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of periodontitis in diabetes.

AIM: The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP-ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor. MATERIALS AND METHODS: Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5-isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP-ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro-CT analyses. RESULTS: Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine-positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor. CONCLUSIONS: These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.

Technical Performance and Clinical Effectiveness of Drop Type With Adjustable Concentrator-Cell Free and Concentrated Ascites Reinfusion Therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is a very useful treatment method for refractory ascites but is difficult for many hospitals to employ due to its need for specialized equipment. We have therefore developed drop-type with adjustable concentrator CART (DC-CART) that uses a drop-type filtration mechanism and requires only a simple pump and pressure monitor for its concentration process. Easy adjustment of ascites concentration is possible through a recirculation loop, and filter membrane washing is aided by DC-CART's external pressure-type filtration to enable the processing of any quality or quantity of ascites. Moreover, the absence of a roller pump before filtration avoids inflammatory substance release from compressed cells. A total of 268 sessions of DC-CART using ascites from 98 patients were performed with good clinical results at our hospitals between January 2012 and June 2016. This report presents the detailed methods of DC-CART and summarizes its clinical effectiveness using patient ascites and blood data obtained from 59 sessions between March 2015 and February 2016. This novel technique successfully processed refractory ascites in numerous diseases with no serious adverse events. DC-CART could concentrate large amounts of ascites (from median weight: 4900 g [max: 20 200 g] to median weight: 695 g; median concentration ratio: 7.4), and a high amount of protein (median weight: 73 g [max: 294 g]) could be reinfused. Serum albumin levels were significantly increased (P = 0.010) and kidney function and systemic hemodynamics were well maintained in treated subjects. Additional concentration of ascites and adjustment of ascites volume were easily performed by recirculation (from median weight: 615 g to median weight: 360 g; median concentration ratio: 1.5). Time was needed during DC-CART for filter membrane cleaning, especially for viscous ascites. Overall, DC-CART represents a safe and useful treatment method for various forms of refractory ascites that can be performed at a wide range of health care institutions.

Congenital nephrotic syndrome with a novel NPHS1 mutation.

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessive disorder. The incidence of CNF is relatively high in Finland but considerably lower in other countries. We encountered a male newborn with CNF, associated with compound heterozygous mutations in nephrosis 1, congenital, Finnish type (NPHS1). The patient was admitted to hospital as a preterm infant. Physical and laboratory findings fulfilled the diagnostic criteria of nephrotic syndrome, and were compatible with a diagnosis of CNF, but there was no family history of the disease. On genetic analysis of NPHS1 a paternally derived heterozygous frame-shift mutation caused by an 8 bp deletion, resulting in a stop codon in exon 16 (c.2156-2163 delTGCACTGC causing p.L719DfsX4), and a novel, maternally derived nonsense mutation in exon 15 (c.1978G>T causing p.E660X) were identified. Early genetic diagnosis of CNF is important for proper clinical management and appropriate genetic counseling.

Reduction in glutamine/glutamate levels in the cerebral cortex after adrenocorticotropic hormone therapy in patients with west syndrome.

West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy (¹H-MRS). In six patients with cryptogenic WS, we performed single-voxel ¹H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients.

The diagnostic utility of exome sequencing in Joubert syndrome and related disorders.

Joubert syndrome (JS) and related disorders (JSRD) are autosomal recessive and X-linked disorders characterized by hypoplasia of the cerebellar vermis with a characteristic 'molar tooth sign' on brain imaging and accompanying neurological symptoms including episodic hyperpnoea, abnormal eye movements, ataxia and intellectual disability. JSRD are clinically and genetically heterogeneous, and, to date, a total of 17 causative genes are known. We applied whole-exome sequencing (WES) to five JSRD families and found mutations in all: either CEP290, TMEM67 or INPP5E was mutated. Compared with conventional Sanger sequencing, WES appears to be advantageous with regard to speed and cost, supporting its potential utility in molecular diagnosis.

Brain magnetic resonance imaging and motor and intellectual functioning in 86 patients born at term with spastic diplegia.

AIM: To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia. METHOD: Eighty-six patients born at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females; median age 20 y, range 7-42 y) among 829 patients with CP underwent brain MRI between 1990 and 2008. The MRI and clinical findings were analysed retrospectively. Intellectual disability was classified according to the Enjoji developmental test or the Wechsler Intelligence Scale for Children (3rd edition). RESULTS: The median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5 mo-8 y), 6 years (2 y 8 mo-19 y), 6 years (1 y 4 mo-19 y), and 7 years (10 mo-30 y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly/periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001). INTERPRETATION: Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology.

Novel and highly reliable leak check tests for drop- and external pressure-type cell-free and concentrated ascites reinfusion therapy.

INTRODUCTION: For safe management of cell-free and concentrated ascites reinfusion therapy (CART), a highly reliable leak test for detecting ascites filter damage is essential. However, such a test has not been established for drop-type CART. METHODS: We devised two novel leak tests for drop- and external pressure-type CART, manual or pump pressurization methods, using high-pressure loading and pressure monitoring, and investigated their reliability. RESULTS: Both methods could easily load and maintain sufficiently high pressure (>400 Torr) on the hollow fibers for 2 min. No result deviation was noted between different operators. The pressure drops in both methods were identical and significantly lower than those in the leak test using a special CART machine, the e-CART. CONCLUSION: The reliability of our revised leak test is equivalent to that of the automatic leak test of e-CART. These highly reliable leak tests may contribute to safety in patients undergoing drop- and external pressure-type CART.

Oxidative stress induces MUC5AC expression through mitochondrial damage-dependent STING signaling in human bronchial epithelial cells.

Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI-H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real-time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP-AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2-induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild-type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.

DNA methylation changes between relapse and remission of minimal change nephrotic syndrome.

BACKGROUND: DNA methylation of gene promoters is associated with transcriptional inactivation. Changes in DNA methylation can lead to differences in gene expression levels and thereby influence disease development. We hypothesized that epigenetics underlies the pathogenesis of minimal change nephrotic syndrome (MCNS). METHODS: Genome-wide DNA methylation changes between relapse and remission in monocytes (n = 6) and naive T helper cells (Th0s) (n = 4) isolated from patients with MCNS were investigated using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. We confirmed the MIAMI results using bisulfite-pyrosequencing analysis. Expression analysis was performed using quantitative real-time PCR. RESULTS: Three gene loci (GATA2, PBX4, and NYX) were significantly less methylated in Th0s during relapse than in remission, compared to none in monocytes. In addition, the distance distribution from the regression line of all probes in MIAMI was significantly different between monocytes and Th0s. The mRNA levels of the three genes in Th0s were not significantly different between relapse and remission. CONCLUSIONS: Our results demonstrate that the change in DNA methylation patterns from remission to relapse in MCNS occurs predominantly in Th0s rather than in monocytes and suggest that epigenetic regulation in Th0s underlies the pathogenesis of MCNS.

Involvement of nitrosative stress in experimental periodontitis in diabetic rats.

AIM: Periodontal disease is highly prevalent and severe in diabetic patients, and is considered one of the diabetic complications. To elucidate how periodontitis progresses in diabetes, we examined an animal model of periodontitis in diabetic rats. MATERIALS AND METHODS: Two weeks after the induction of diabetes by streptozotocin, surgical nylon thread was ligated around the cervical portion of the unilateral maxillary second molar to induce periodontitis. Periodontitis was evaluated 2 weeks after the ligation by gingival blood flow, mRNA expressions, Western blot analysis, histological examination and micro CT. RESULTS: Ligation-induced severe periodontitis in the diabetic rats, which was apparently shown by the increase of TNF-α and iNOS mRNA expressions and inflammatory cell infiltration in the gingiva and alveolar bone loss. The number of nitrotyrosine, a footprint of nitrosative stress, -positive cells was significantly higher in the periodontitis of the diabetic rats compared with that in the normal rats. Western blot analysis confirmed that the nitrotyrosine was increased in the periodontitis of the diabetic rats. CONCLUSIONS: This is the first study to confirm increased nitrosative stress due to periodontitis in diabetic rats. Nitrosative stress may play a crucial role in the exacerbation of periodontitis in diabetic patients.

Systemic Lupus Erythematosus Presenting With Thrombotic Thrombocytopenic Purpura at Onset: A Case Report.

Background: Thrombotic microangiopathy (TMA) is a syndrome associated with hemolytic anemia, thrombocytopenia, and various organ disorders. Thrombotic thrombocytopenic purpura (TTP) is a disease that develops when a disintegrin-like and metalloproteinase with thrombospondin type l motif 13 (ADAMTS13) activity decreases to < 10% of that in normal plasma, causing platelet thrombosis in microvessels throughout the body. Currently, ADAMTS13-deficient TMA is diagnosed as TTP. Systemic lupus erythematosus (SLE)-related TMA includes both acquired TTP, in which ADAMTS13 activity is significantly reduced, and secondary TMA, in which ADAMTS13 activity is not reduced. Both diseases have different prognoses. Case Presentation: An 11-year-old girl was admitted to our hospital on suspicion of TMA with thrombocytopenia and hemolytic anemia. Because the patient had hypocomplementemia, SLE-related TMA or complement-related TMA was considered. Therefore, we initiated plasma exchange (PE) for the patient. Subsequently, she fulfilled the pediatric SLE diagnostic criteria, and ADAMTS13 activity was shown to be decreased and the anti-ADAMTS13 antibody titer increased. She was thus diagnosed with acquired TTP caused by SLE. Treatment response was good as a platelet count and ADAMTS13 activity improved with three times of PE, followed by methylprednisolone pulse therapy and administration of mycophenolate mofetil. Renal pathology showed thrombus formation in glomerular arterioles and lupus nephritis categorized as Class III (A) of the International Society of Nephrology and the Renal Pathology Society classification. Because the patient was thought to be in the high-risk group of SLE, three courses of intravenous cyclophosphamide pulse therapy were administered as an additional induction therapy. No recurrence of TTP was observed. Conclusion: In SLE-related TMA, measurement of ADAMTS13 activity and the anti-ADAMTS13 antibody titer are necessary for diagnosis, and for predicting prognosis and recurrence of the disease; however, in the acute phase of immune-mediated TMA, it is important to initiate proper treatments even before knowing the results to improve prognosis.

Any modality of renal replacement therapy can be a treatment option for Joubert syndrome.

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the "molar tooth sign" on axial brain images, hypotonia, and developmental delay. Approximately 25-30% of patients with JS have kidney disease and many of them progress to end-stage kidney disease (ESKD). However, there are few reports on the outcomes of renal replacement therapy (RRT) in patients with JS and ESKD. In this study, we clarified the clinical features, treatment, and outcomes of patients with JS who underwent RRT. We retrospectively analyzed the medical records and clinical characteristics of 11 patients with JS who underwent RRT between June 1994 and July 2019. Data are shown as the median (range). Gene analysis was performed in 8 of the 11 cases, and CEP290 mutations were found in four patients, two had TMEM67 mutations, one had a RPGRIP1L mutation, and one patient showed no mutation with the panel exome analysis. Complications in other organs included hydrocephalus in two cases, retinal degeneration in eight cases, coloboma in one case, liver diseases in four cases, and polydactyly in one case. Peritoneal dialysis (PD) was introduced in seven cases, with a median treatment duration of 5.4 (3.4-10.7) years. Hemodialysis was performed using arteriovenous fistula in two cases, and kidney transplantation was performed 9 times in eight cases. Only one of the grafts failed during the observation period of 25.6 (8.2-134.2) months. The glomerular filtration rate at the final observation was 78.1 (41.4-107.7) mL/min/1.73 m2. The median age at the final observation was 13.4 (5.6-25.1) years, and all patients were alive except one who died of hepatic failure while on PD. Any type of RRT modality can be a treatment option for patients with JS and ESKD.

Sustainable Effects of Human Dental Pulp Stem Cell Transplantation on Diabetic Polyneuropathy in Streptozotocine-Induced Type 1 Diabetes Model Mice.

Dental pulp stem cells (DPSCs) are suitable for use in regenerative medicine. Cryopreserved human DPSCs (hDPSCs) ameliorate diabetic polyneuropathy, and the effects of hDPSC transplantation are related to VEGF and NGF secretion. This study evaluated the long-term effects of a single transplantation of hDPSCs on diabetic polyneuropathy. hDPSCs were obtained from human third molars extracted for orthodontic treatment, which were then transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocin injection in nude mice. The effects of hDPSC transplantation were analyzed at 16 weeks post-transplantation. DPSC transplantation significantly improved delayed nerve conduction velocity, decreased blood flow, and increased sensory perception thresholds. Furthermore, the hDPSC-conditioned medium promoted the neurite outgrowth of dorsal root ganglion neurons. In conclusion, the therapeutic effects of hDPSC transplantation with a single injection last for prolonged periods and may be beneficial in treating long-term diabetic polyneuropathy.