Botrytis cinerea detoxifies the sesquiterpenoid phytoalexin rishitin through multiple metabolizing pathways.

Botrytis cinerea is a necrotrophic pathogen that infects across a broad range of plant hosts, including high-impact crop species. Its generalist necrotrophic behavior stems from its ability to detoxify structurally diverse phytoalexins. The current study aims to provide evidence of the ability of B. cinerea to tolerate the sesquiterpenoid phytoalexin rishitin, which is produced by potato and tomato. While the growth of potato pathogens Phytophthora infestans (late blight) and Alternaria solani (early blight) was severely inhibited by rishitin, B. cinerea was tolerant to rishitin. After incubation of rishitin with the mycelia of B. cinerea, it was metabolized to at least six oxidized forms. Structural analysis of these purified rishitin metabolites revealed a variety of oxidative metabolism including hydroxylation at C7 or C12, ketone formation at C5, and dihydroxylation at the 10,11-olefin. Six rishitin metabolites showed reduced toxicity to P. infestans and A. solani, indicating that B. cinerea has at least 5 distinct enzymatic reactions to detoxify rishitin. Four host-specialized phytopathogenic Botrytis species, namely B. elliptica, B. allii, B. squamosa, and B. tulipae also had at least a partial ability to metabolize rishitin as B. cinerea, but their metabolic capacity was significantly weaker than that of B. cinerea. These results suggest that the ability of B. cinerea to rapidly metabolize rishitin through multiple detoxification mechanisms could be critical for its pathogenicity in potato and tomato.

Single measurement of bowel wall thickness using intestinal ultrasonography in children with ulcerative colitis.

BACKGROUND: Endoscopic monitoring of disease activity in patients with ulcerative colitis (UC) is important. However, frequent colonoscopic examinations are difficult to perform because of their invasiveness, especially in children. Bowel wall thickness (BWT) measurement using intestinal ultrasonography and fecal calprotectin (FC) measurement are useful noninvasive evaluation methods. METHODS: We retrospectively analyzed BWT and FC levels and evaluated the Mayo endoscopic subscore (MES) using colonoscopy in pediatric patients with UC during the same period. The BWT was evaluated using the maximum BWT (mBWT), which was the maximum value of each colonic BWT; the sum of BWT (sBWT), which was the sum of each colonic BWT; and the sum of the adjusted BWT (saBWT), which was corrected using sBWT. RESULTS: In 54 procedures from 40 patients, FC, mBWT, sBWT, and saBWT were significantly different between MES 0-1 and MES 2. The agreement between BWT and MES 2 was 193 out of 216 segments (89.4%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FC were 68.8%, 84.2%, 64.7%, 86.5%, and 79.6% respectively, while those of saBWT were 81.2%, 89.5%, 76.5%, 91.9%, 87.0%, respectively. CONCLUSIONS: BWT in each colonic segment, particularly saBWT, was more useful than FC for detecting moderate colonic inflammation (MES 2) in pediatric patients with UC. Therefore, intestinal ultrasonography may be helpful in the less invasive management of pediatric patients with UC.

Association of adolescent postural tachycardia syndrome classifications with anxiety: a cross sectional study.

BACKGROUND: Postural tachycardia syndrome (POTS), a subset of orthostatic dysregulation, has been reported to be associated with anxiety. POTS can be classified into two forms based on the degree of tachycardia during orthostasis. Reportedly, POTS with decreased orthostatic heart rate increase is associated with suppressed cardiac parasympathetic activity and increased sympathetic activity in the supine position. In this study, the relationship between the two types of POTS and anxiety was evaluated in terms of autonomic function. METHODS: Fifty-two patients (23 male, age 10-15 years) who were diagnosed with POTS at the Department of Pediatrics, Osaka Medical and Pharmaceutical University from 2019 to 2021, completed a standing test and were accordingly classified into a Su group, with tachycardia from the supine position and a low heart rate increase on standing, a SI group, with a high heart rate increase during standing. They then completed the State-Trait Anxiety Scale for Children (STAIC) questionnaire. Autonomic function was assessed by frequency analysis (MemCalc method) based on heart rate, blood pressure changes, heart rate and blood pressure variability during the orthostatic test. RESULTS: Patients in the Su group had higher trait anxiety and state anxiety, lower cardiac parasympathetic activity (RR-HF) in the supine position, and greater variability in cardiac parasympathetic activity during orthostasis than were found for patients in the SI group. The Su group had a greater decrease in cardiac index on standing than that of the SI group. CONCLUSIONS: The Su group results may be partly attributed to chronically low venous return. We also found that patients in the Su group had low parasympathetic activity in the supine position, which may interact with the anxiety-prone characteristics of these patients. Therefore, it seems necessary to consider both physical and psychosomatic treatment approaches for patients with POTS.

Microvascular Endothelial Function Assessed Using Peripheral Arterial Tonometry in Adolescents with Repaired Congenital Heart Disease.

Atherosclerosis can develop in adult patients with congenital heart disease (CHD) and should be given attention. Endothelial function is well known as a predictor of the development of atherosclerosis but has not been well investigated in patients with repaired CHD. This study aimed to clarify the endothelial function and its relationship with clinical backgrounds and parameters in adolescents with various types of repaired CHDs. Endothelial function was evaluated using peripheral arterial tonometry (PAT). The reactive hyperemia index (RHI) was evaluated and compared between adolescents with repaired CHD and those in the control group. The relationship between the clinical background and parameters was also investigated in patients with repaired CHD. Forty-eight patients with repaired CHD (age 14.0 ± 3.3 years) and 114 healthy volunteers were included in this study. Patients with repaired CHD comprised 16 with repaired non-cyanotic CHD, 14 with repaired tetralogy of Fallot, and 18 who underwent the Fontan procedure. RHI in the repaired CHD group was significantly lower than in the control group. There was no significant correlation between the RHI and blood biochemical markers, such as uric acid, creatine, and brain natriuretic peptide levels. The RHI was significantly higher in patients taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) than in those not taking them. Endothelial function was impaired in adolescents with repaired CHD compared to that in the control group. Microvascular endothelial dysfunction developed even in adolescents with simple non-cyanotic CHD.

Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy.

Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot-Marie-Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotypes.

Botrytis cinerea tolerates phytoalexins produced by Solanaceae and Fabaceae plants through an efflux transporter BcatrB and metabolizing enzymes.

Botrytis cinerea, a plant pathogenic fungus with a wide host range, has reduced sensitivity to fungicides as well as phytoalexins, threatening cultivation of economically important fruits and vegetable crops worldwide. B. cinerea tolerates a wide array of phytoalexins, through efflux and/or enzymatic detoxification. Previously, we provided evidence that a distinctive set of genes were induced in B. cinerea when treated with different phytoalexins such as rishitin (produced by tomato and potato), capsidiol (tobacco and bell pepper) and resveratrol (grape and blueberry). In this study, we focused on the functional analyses of B. cinerea genes implicated in rishitin tolerance. LC/MS profiling revealed that B. cinerea can metabolize/detoxify rishitin into at least 4 oxidized forms. Heterologous expression of Bcin08g04910 and Bcin16g01490, two B. cinerea oxidoreductases upregulated by rishitin, in a plant symbiotic fungus Epichloë festucae revealed that these rishitin-induced enzymes are involved in the oxidation of rishitin. Expression of BcatrB, encoding an exporter of structurally unrelated phytoalexins and fungicides, was significantly upregulated by rishitin but not by capsidiol and was thus expected to be involved in the rishitin tolerance. Conidia of BcatrB KO (ΔbcatrB) showed enhanced sensitivity to rishitin, but not to capsidiol, despite their structural similarity. ΔbcatrB showed reduced virulence on tomato, but maintained full virulence on bell pepper, indicating that B. cinerea activates BcatrB by recognizing appropriate phytoalexins to utilize it in tolerance. Surveying 26 plant species across 13 families revealed that the BcatrB promoter is mainly activated during the infection of B. cinerea in plants belonging to the Solanaceae, Fabaceae and Brassicaceae. The BcatrB promoter was also activated by in vitro treatments of phytoalexins produced by members of these plant families, namely rishitin (Solanaceae), medicarpin and glyceollin (Fabaceae), as well as camalexin and brassinin (Brassicaceae). Consistently, ΔbcatrB showed reduced virulence on red clover, which produces medicarpin. These results suggest that B. cinerea distinguishes phytoalexins and induces differential expression of appropriate genes during the infection. Likewise, BcatrB plays a critical role in the strategy employed by B. cinerea to bypass the plant innate immune responses in a wide variety of important crops belonging to the Solanaceae, Brassicaceae and Fabaceae.

Draft Genome Sequences of Neofusicoccum parvum Strains Isolated from Mango and Rice-Paper Plant (Tetrapanax papyrifer).

Neofusicoccum parvum is a polyxenous phytopathogenic fungus that infects important fruits, such as grapes and mangoes. Here, we report the genome sequences of N. parvum strains that were isolated from mango in Okinawa, Japan (strain PPO83), and an invasive weed (rice-paper plant [Tetrapanax papyrifer]) in Nagoya, Japan (strain NSSI1).

Survival analysis among pediatric patients receiving kidney replacement therapy: a Japanese nationwide cohort study.

BACKGROUND: Limited data are available on the survival and causes of death in pediatric patients with chronic kidney disease (CKD) stage 5 receiving kidney replacement therapy (KRT) in Asia. METHODS: Data were obtained from the Japanese nationwide cross-sectional CKD stage 5 survey on pediatric patients (<20 years of age) who started KRT from 2006 to 2013. The cohort was divided into three groups according to age at the start of KRT: <1, 1-5, and 6-19 years. RESULTS: Among the 701 children who were included, 59.3% were boys. Peritoneal dialysis was the most common initial modality of KRT (60.3%). Median age at KRT initiation was 10.2 years. Infants (<1 year old) accounted for 16.0% of the total cohort. Overall survival at 1 and 5 years was 97.2% and 92.5%, respectively. Infants had significantly lower survival rates than the other groups (hazard ratio, 5.35; 95% CI, 2.60-11.03; P < 0.001). In contrast, after the age of 1 year, the survival rate improved and did not differ from that of other age groups. The most common causes of death were infection (35.9%) and sudden death (15.4%). CONCLUSIONS: The overall survival rate of pediatric patients with CKD stage 5 in Japan is like that in other high-income countries. Age at initiation of KRT is an important factor affecting survival since the poorest survival rate was observed in infants. Further improvement in infant dialysis therapy is still needed to improve survival of the youngest children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan.

BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin-producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated. RESULTS: A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab. CONCLUSION: Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan.

A glucocorticoid-receptor agonist ameliorates bleomycin-induced alveolar simplification in newborn rats.

BACKGROUND: Glucocorticoids (GCs) are highly effective yet problematic agents against bronchopulmonary dysplasia (BPD). The dimeric trans-activation of GCs induces unfavorable effects, while monomeric trans-repression suppresses inflammation-related genes. Recently, non-steroidal-selective glucocorticoid-receptor agonists and modulators (SEGRAMs) with only the trans-repressive action have been designed. METHODS: Using a bleomycin (Bleo)-induced alveolar simplification newborn rat model (recapitulating arrested alveolarization during BPD), we evaluated the therapeutic effects of compound-A (CpdA), a SEGRAM. Sprague-Dawley rats were administered Bleo from postnatal day (PD) 0 to 10 and treated with dexamethasone (Dex) or CpdA from PD 0 to 13. The morphological changes and mRNA expression of inflammatory mediators, including interleukin (IL)-1ß, C-X-C motif chemokine ligand 1 (CXCL1), and C-C motif chemokine 2 (CCL2) were investigated. RESULTS: Similar to the effects of Dex, CpdA exerted protective effects on morphological derangements and inhibited macrophage infiltration and production of pro-inflammatory mediators in Bleo-treated animals. The effects of CpdA were probably mediated by GC receptor (GR)-dependent trans-repression, because unlike the Dex-treated group, anti-inflammatory genes specifically induced by GR-dependent trans-activation (such as "glucocorticoid-induced leucine zipper, GILZ") were not upregulated. CONCLUSIONS: CpdA improved lung inflammation, inhibited the arrest of alveolar maturation, and restored histological and biochemical changes in a Bleo-induced alveolar simplification model. IMPACT: SEGRAMs have attracted widespread attention because they are expected to not exhibit unfavorable effects of GCs. Compound A, one of the SEGRAMs, improved lung morphometric changes and decreased lung inflammation in a bleomycin-induced arrested alveolarization, a newborn rat model representing one of the main features of BPD pathology. Compound A did not elicit bleomycin-induced poor weight gain, in contrast to dexamethasone treatment. SEGRAMs, including compound A, may be promising candidates for the therapy of BPD with less adverse effects compared with GCs.

Comparison of outcomes after plasma therapy or eculizumab in pediatric patients with atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare and life-threatening disease. For decades, plasma therapy was used to manage patients with aHUS. Since eculizumab, a recombinant humanized anti-C5 monoclonal antibody, was approved for treatment of aHUS, it has been used to treat patients with aHUS. Here, we examined the effectiveness of eculizumab and plasma therapy, respectively in the treatment of pediatric patients with aHUS. METHODS: Data were collected from questionnaires sent to 75 institutions known to be treating thrombotic microangiopathy (TMA). RESULTS: A total of 24 patients were evaluable, in which no recurrence of TMA was reported at last observation. There were four therapy groups: two patients receiving supportive therapy, one receiving plasma therapy alone, 17 switching from plasma therapy to eculizumab (therapy switched), and four receiving eculizumab alone. Among 17 patients of therapy-switched group, only one patient achieved complete remission at the end of plasma therapy, 15 patients achieved complete remission after eculizumab initiation, and two patients reached end-stage renal disease. Adverse events were reported in nine cases; among these, meningococcal infection, anaphylaxis, and eculizumab-related infusion reaction were reported among those treated with eculizumab. CONCLUSION: This study provided substantial evidence from a Japanese population that the conversion from plasma therapy to eculizumab therapy should be considered in patients with aHUS who show an incomplete response to plasma therapy. In addition, although no new safety events were detected, careful attention should be paid to meningococcal infection, eculizumab-related infusion reactions and allergic reactions with administration of eculizumab.

Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.

BACKGROUND: Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. METHODS: This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. RESULTS: The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. CONCLUSION: The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.

A comparative analysis of children born with low birthweight and attention deficit hyperactivity disorder.

BACKGROUND: We aimed to compare the profile of the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) between Japanese schoolchildren born very preterm (VP) and with very low birthweight (VLBW) and those with attention deficit hyperactivity disorder (ADHD), and to identify the specific neurocognitive characteristics of VLBW/VP children. METHODS: The VLBW/VP group in the present study included 50 (19 male, 31 female) first- to third-grade elementary school children born between January 2008 and February 2013 at Osaka Medical and Pharmaceutical University Hospital and Saiseikai Suita Hospital with birthweights <1,500 g and <32 gestational weeks. The ADHD group included 18 (13 male, 5 female) first- to third-grade elementary school children who visited Osaka Medical and Pharmaceutical University Hospital between January 2019 and October 2021. Full-scale intelligence quotient scores, four indices, and 12 subtests of the WISC-IV were calculated for all participants and compared between the VLBW/VP and ADHD groups. We assessed whether the patients' clinical history was associated with a low score on the cancellation task in the VLBW/VP group. RESULTS: The WISC-IV profiles showed similar between-group patterns, and the VLBW/VP group had lower cancellation task scores than the ADHD group. CONCLUSIONS: This is the first study to compare WISC-IV profiles between VLBW/VP children and those with ADHD. Further investigation is needed on the association between academic performance and the score of the cancellation task, and the neural mechanism of low performance for cancellation tasks in VLBW/VP children.

Impacts of long-term coronavirus disease 2019 school closures on Japanese school children.

BACKGROUND: This study investigated the impact of coronavirus disease 2019 pandemic school closures on the mental health of school students with chronic diseases. METHODS: Questionnaires were distributed to students from 4th-9th grade diagnosed with chronic diseases at Osaka Medical College Hospital and their parents or caregivers. Questionnaires from 286 families were returned by mail after the schools reopened. The students were divided into the "psychosomatic disorder" group (group P, n = 42), the "developmental disorder" group (group D, n = 89), and the "other disease" group (group O, n = 155). Using students' self-reports on the Questionnaire for Triage and Assessment with 30 items, we assessed the proportion of students with a high risk of psychosomatic disorder in three groups. We investigated how the students requiring the support of somatic symptom (SS) felt about school during school closure. Further, using parents' and caregivers' answers, SS scores were calculated before and during school closure and after school reopening. RESULTS: The proportion of students with a high risk of developing psychosomatic disorder increased in all groups. For the students in Group P, the response "I did not want to think about school" indicated an increase in SS scores, and for the students in Group O, "I wanted to get back to school soon" indicated a decrease. Furthermore, especially in Group P students, SS scores decreased transiently during school closure and increased after school reopening. CONCLUSIONS: The impact of school closure on mental health differed depending on students' diagnoses and feelings about school during school closures.

Usefulness of ultrasonography for small intestinal evaluations in pediatric Crohn's disease.

BACKGROUND: Small bowel capsule endoscopy (SBCE) for Crohn's disease is useful; however, its use has some limitations, such as invasiveness when endoscopic assistance is required in patients who cannot swallow the capsule, and the burden of interpretation on a physician. In contrast, intestinal ultrasonography (IUS) is a non-invasive modality for children. The purpose of this study is to evaluate the accuracy of IUS for pediatric patients with established Crohn's disease. METHODS: Small bowel capsule endoscopy and IUS findings from the same period in pediatric patients with established Crohn's disease were analyzed retrospectively. First, we compared the Lewis score (LS), small bowel endoscopic activity, and IUS findings by small bowel wall thickness (SBWT) and mesenteric lymph node size (MLNS). Second, we compared the performance of IUS findings with those of some biomarkers. RESULTS: In 22 procedures, SBWT and MLNS were correlated with LS (r = 0.52, P < 0.05, and r = 0.45, P < 0.05, respectively). Small bowel wall thickness, erythrocyte sedimentation rate, and fecal calprotectin levels had the highest accuracy (81.8%, 81.8%, and 81.8%, respectively). The combination of SBWT and MLNS had the highest positive predictive value and negative predictive value (100% and 83.3%, respectively). CONCLUSIONS: Intestinal ultrasonography findings, including SBWT and MLNS, are useful for monitoring small bowel lesions in pediatric patients with established Crohn's disease. We suggest first evaluating small bowel inflammation by IUS in pediatric patients with Crohn's disease before SBCE because IUS is less invasive than SBCE.

Focal seizures during adrenocorticotropic hormone therapy in a school-aged boy: a case report.

BACKGROUND: Adrenocorticotropic hormone therapy for infantile spasms, including West syndrome, has been previously reported to induce seizures. We present the findings for a school-aged child with epilepsy who developed new focal seizures during adrenocorticotropic hormone therapy. CASE PRESENTATION: The Japanese patient had posttraumatic epilepsy and developed intractable focal seizures at the age of 13 years. Adrenocorticotropic hormone therapy was administered when the patient was 14 years of age. On day 10 of treatment, he developed new focal seizures, which were characterized by left arm contractions followed by movements of touching things with his right hand and writhing and rocking his body left and right and back and forth as automatisms. The focal seizures clustered for 40 minutes and disappeared after suppository administration of 10 mg diazepam. These focal seizures did not reoccur after more than 2 years of follow-up. CONCLUSION: Adrenocorticotropic hormone-induced seizures can occur in children older than previously reported, and can occur in children with intractable seizures other than epileptic spasms.

A Case of Gorlin-Goltz Syndrome Without the Characteristic Physical Features That Was Diagnosed After the Development of a Fifth Cancer.

We present a case of Gorlin-Goltz syndrome (GGS) in a patient who developed medulloblastoma, osteosarcoma, myelodysplastic syndrome, basal cell carcinoma, and odontogenic keratocyst by the age of 19 years. He had no known family history and no characteristic physical features of GGS. A frameshift mutation in the PTCH1 gene was found in the oral mucosa as a low-frequency mosaicism, basal cell carcinoma, and normal skin by whole exome sequencing of cancer susceptibility genes. Setting a therapeutic strategy with regard to second cancer development is important for pediatric cancer patients who have a background of cancer predisposition. Advances in comprehensive multigenetic analysis are anticipated to aid in developing such a strategy.

Serum sodium level is inversely correlated with body temperature in children.

BACKGROUND: Several studies have demonstrated that non-osmotic antidiuretic hormone activity contributes to the development of hyponatremia in children with common febrile diseases. However, the relationship between hyponatremia and body temperature has remained unclear. We therefore examined this relationship in children with common diseases. METHODS: In this retrospective case study based on a chart review, 1,973 children presenting with acute illnesses at Hirakata City Hospital between November 2008 and October 2009, and for whom blood test data were available, were enrolled. The median age of this cohort was 2.7 years and the mean serum sodium concentration was 136.4 mEq/L; 454 patients showed hyponatremia (<135 mEq/L). The patients were classified into four groups on the basis of body temperature, <37 °C, 37 °C (37.0-37.9 °C), 38 °C (38.0-38.9 °C) and ≥39 °C, and their serum sodium concentration was compared. RESULTS: The mean sodium level was significantly lower in febrile (135.9 mEq/L) than in non-febrile (138.5 mEq/L) patients. The mean serum sodium levels in the four temperature groups were, in ascending order, 138.5 mEq/L (95% CI, 138.3-138.8 mEq/L), 137.3 mEq/L (137.1-137.5 mEq/L), 136.1 mEq/L (135.8-136.3 mEq/L) and 134.6 mEq/L (134.4-134.9 mEq/L), respectively. The serum sodium level in each individual temperature range became significantly lower as body temperature increased (P < 0.001). CONCLUSIONS: There is a clear inverse correlation between serum sodium level and body temperature in children with common febrile diseases, and fever may play an important role in this relationship.