Risk Factor Analysis of Lymph Node Metastasis for Rectal Neuroendocrine Tumors: Who Needs a Radical Resection in Rectal Neuroendocrine Tumors Sized 1-2 cm?

BACKGROUND: Rectal neuroendocrine tumors (NETs) have malignant potential, and lymph node (LN) or distant metastases can occur; however, treatment of NETs 1-2 cm in size is controversial. OBJECTIVE: This study aimed to identify predictive factors for LN metastasis and prognostic factors for recurrence of rectal NETs, especially tumors 1‒2 cm in size. METHODS: Between October 2004 and November 2020, 453 patients underwent endoscopic or surgical treatment for rectal NETs in Seoul National University Hospital. The data on these patients were prospectively collected in our database and reviewed retrospectively. In cases of local excision, we evaluated LN metastasis with radiologic imaging, including computed tomography or magnetic resonance imaging before treatment and during the follow-up periods. RESULTS: LN metastasis was observed in 40 patients (8.8%). A higher rate of LN metastasis was observed in larger-sized tumors, advanced T stage, lymphovascular invasion (LVI), perineural invasion (PNI), and high tumor grade. In multivariable analysis, the significant risk factors for LN metastasis were tumor size (1 ≤ size < 2 cm: hazard ratio [HR] 64.07; size ≥2 cm: HR 102.37, p < 0.001) and tumor grade (G2: HR 3.63, p = 0.034; G3: HR 5.09, p = 0.044). In multivariable analysis for tumors 1-2 cm in size, the risk factor for LN metastasis was tumor grade (G2: HR 6.34, p = 0.013). CONCLUSIONS: Tumor grade and size are important predictive factors for LN metastasis. In NETs 2 cm in size, tumor grade is also important for LN metastasis, and radical resection should be considered.

Angiotensin receptor blockers, but not angiotensin-converting enzyme inhibitors, inhibit abnormal bone changes in spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disease that results in bone ankylosis. The tissue renin-angiotensin system (RAS) is an emerging pathway potentially implicated in SpA-associated bone changes. The aim of the present study was to determine the mechanisms underlying this relationship. Sakaguchi (SKG) mice injected with curdlan (SKGc), animal models for SpA, were treated with RAS modulators, angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis). Disease activity was assessed using clinical scores and computed tomography scans. Mouse primary bone marrow monocytes (BMMs), osteoblast (OB) progenitor cells, peripheral blood monocytes (PBMCs), and bone-derived cells (BdCs) from patients with radiographic axial SpA (r-axSpA) were used to investigate the role of RAS in SpA pathogenesis. The expression of RAS components was significantly increased in SKGc mouse joints, and ARBs significantly reduced erosion and systemic bone loss, whereas ACEis did not. Osteoclast (OC) differentiation from primary BMMs, mediated by TRAF6, was inhibited by ARBs but promoted by ACEis; the modulators also exerted opposite effects on OB differentiation. Expression of RAS molecules was higher in PBMCs and BdCs of patients with r-axSpA than in control participants. ARBs inhibited OB differentiation in the BdCs of patients with r-axSpA, whereas ACEis did not. Neither ARBs nor ACEis affected OB differentiation in the control participants. In SpA, a condition characterized by RAS overexpression, ARBs, but not ACEis, inhibited OC and OB differentiation and bone progression. The findings should be taken into account when treating patients with SpA using RAS modulators.

A 3 mm Port Reduces Postoperative Pain After Laparoscopic Colon Cancer Surgery: A Case-control Matched Study.

BACKGROUND: Recently, smaller-size trocars and instruments have been developed for laparoscopic colon cancer surgery; however, their effectiveness and safety have not been elucidated. This study aimed to investigate whether 3 mm trocars and instruments have benefits compared with conventional trocars and instruments. PATIENTS AND METHODS: Patients with colon cancer who underwent laparoscopic anterior resection or right hemicolectomy were included. Patients who underwent combined resections of other organs and those with conversion to open surgery were excluded. In the 3 mm group, three 5 mm trocars were replaced by 3 mm trocars. The numeric rating scale (NRS) immediately postoperatively at 24, 48, and 72 hours, respectively, after surgery and the use of additional analgesics and perioperative outcomes were analyzed. Case-control matched analysis was used to reduce bias according to the type of surgery. RESULTS: A total of 207 patients (conventional: n = 158, 3 mm: n = 49) were included. Before matching, NRS 48 hours postoperatively ( P = 0.049), proportion of patients using additional intravenous (IV) analgesics ( P = 0.007), postoperative hospital stay ( P < 0.001), and blood loss ( P < 0.001) were lower in the 3 mm group. In multivariable analysis, trocar type significantly impacted the proportion of patients using additional IV analgesics (odds ratio: 0.330; 95% CI: 0.153-0.712; P = 0.005). After case-control matching, NRS immediately postoperatively ( P = 0.015) and 24 hours postsurgery ( P = 0.043), patients using additional IV analgesics ( P = 0.019), postoperative hospital stay ( P = 0.010), intraoperative blood loss ( P < 0.001), and postoperative complication rate ( P = 0.028) were significantly lower in the 3 mm group compared with the 5 mm group. CONCLUSIONS: The use of 3 mm trocars and instruments in laparoscopic colon cancer surgery can effectively reduce postoperative pain while maintaining perioperative safety.

The Association between Dental Implant Treatment Experience and Socioeconomic Factors in Korean Adults: A Cross-Sectional Survey Data Analysis.

Background: We examined the Korean adults' experience with dental implants and analyzed its association with various socioeconomic factors. Methods: This study was based on the participants enrolled in the 2013-2015 KNHANES. Using the variables associated with dental implant treatment experience and other socioeconomic factors, we evaluated the statistical significance and potential associations between the dental implant treatment experience and its related factors. The final analysis in this study was performed on adults aged 20 yr and over. It comprised 4,893 subjects in the year 2013, 4,431 subjects in 2014, and 4,430 subjects in 2015. Results: An increasing number of individuals had reported undergoing dental implant treatment. An older age was associated with a higher likelihood of undergoing dental implant treatment, particularly in adults aged ≥40 years. Additionally, the likelihood was higher in individuals with a greater income level, low-level of educational background, and married status. Factors that were observed to influence dental implant treatment experience included age, education level, income level, marital status. Conclusion: Our analysis confirmed the growing accessibility to dental implants among Korean adults and an association between dental implant treatment experience and socioeconomic factors. We recommend a healthcare policy on dental implants that considers relevant socioeconomic factors, in order to provide dental implant treatment to individuals who are in absolute need of treatment.

Effects of Problem-Based Learning on the Problem-Solving Ability and Self-Efficacy of Students Majoring in Dental Hygiene.

This study developed a problem-based learning (PBL) module to improve integrated thinking and problem-solving ability in students of dental hygiene. After applying PBL, the study tested the improvement in the problem-solving ability and self-efficacy of students. The subjects were 31 fourth-year students of the Department of Dental Hygiene at G University. The PBL process was applied to three topics for 15 weeks, and the tools for evaluating problem-solving ability and self-efficacy were reconstructed and used before and after the application to examine the effects of the module. The result indicates that the mean of problem-solving ability (32 detailed items) increased from 3.37 to 3.65 (an increase of 0.28) after classes (p < 0.001). Alternatively, the average for self-efficacy (22 detailed questions) increased from 0.21 to 2.89 (p < 0.05; an increase of 2.67). The study also confirmed the correlation between problem-solving ability and the total posttest score for self-efficacy (p < 0.001). Thus, the problem-solving ability and self-efficacy of learners were improved in the class to which PBL was applied. These improvements exerted a significant effect on the improvement of problem-solving ability. This finding confirmed the effect of the PBL method on dental hygiene education.

Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. METHODS: A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. RESULTS: The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p = .003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p < .001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p = .003). Overall, the graft survival rate was inferior in the high IPV group (p < .001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p < .001). CONCLUSION: The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.

Has the Health Insurance Coverage of Scaling Contributed Positively to Periodontal Health in Korea?

This study aimed to evaluate the effectiveness of the health insurance coverage of dental scaling (introduced in 2013) using the Community Periodontal Index of Treatment Needs parameter among Korean adults aged 20 years or older. We used the Korea National Health and Nutrition Examination Survey data from before and after 2013 to analyze the statistical significance and associations of the covariates with the prevalence of healthy periodontal tissues, prevalence of people in need of scaling, and prevalence of periodontal diseases. The results showed that the prevalence of healthy periodontal tissues increased by 4.9% (from 34.2% to 39.1%), the number of people in need of scaling decreased by 5% (from 65.9% to 60.9%), and the prevalence of periodontal diseases increased by 7.2% (from 23.4% to 30.6%). Moreover, after the scaling coverage policy, the odds ratio of the prevalence of healthy periodontal tissues was 1.10 times higher, the prevalence of the need for scaling was 1.5 times higher, and the prevalence of periodontal diseases was 0.90 times lower. Therefore, the state should formulate policies that provide dental biofilm management through a disclosing agent, impart education about oral hygiene, and develop a health management system that enables the concurrent management of periodontal diseases and systemic diseases.

The Impact of Expanded National Health Insurance Coverage of Dentures and Dental Implants on Dental Care Utilization among Older Adults in South Korea: A Study Based on the Korean Health Panel Survey.

In South Korea, the National Health Insurance Service (NHIS) began its coverage of dentures and dental implants for older people in 2012 and 2014, respectively. This study aimed to investigate the impact of these policies on dental care utilization among people aged 65 years or older according to their sociodemographic characteristics. Data were collected from the Korea Health Panel Survey (KHP; years 2012 and 2015). The statistical significance of the relationships between sociodemographic characteristics and the use of outpatient dental care, denture, and dental implant were analyzed. Results showed an increase of 5.7%, 1.4%, and 2.8% in the use of outpatient dental care, denture, and dental implant, respectively, over the course of three years. Including dentures increased its use by 2.5-3.7 times among people aged 70 years or older. Including dental implants alleviated the disparities among older adults based on age groups and duration of education, except those among uneducated people; however, it caused inequity according to household income. Some Korean older adults remain neglected from the benefits of the expanded NHIS. Therefore, older adults' access to dental care should be enhanced by the implementation of policies to promote oral health care utilization, dental prosthetic services, and older adults' insurance coverage.

Changes in oral health indicators due to implementation of the National Health Insurance Services coverage for first molar dental sealant for children and adolescents in South Korea.

BACKGROUND: In South Korea, dental sealant was included in the National Health Insurance Services (NHIS) coverage for the first molar for ages 6-14 in December 2009. The second molar was included in 2012, and the age of insurance coverage was extended to under 18 in 2013. This study aimed to verify the effectiveness of an NHIS dental sealant coverage policy for children and adolescents by comparing the changes in first molar oral health indicators before and after policy implementation. METHODS: The Korea National Health and Nutrition Examination Survey data were analyzed; the fourth period (2007-2009) provided data for before and the sixth period (2013-2015) provided data for after policy implementation. The proportion of individuals with first-molar sealant, decay-missing-filled first molar permanent teeth, and single crowns in the group aged 11-20 years were calculated. Data were analyzed using chi-square for complex samples and the complex samples general linear model. In addition, complex-sample logistic regression analysis was performed to confirm the association between factors. RESULTS: Compared with non-beneficiaries, among policy beneficiaries, sealant ownership increased by 7.7% (from 27.8 to 35.5, P < 0.001), and the number of permanent teeth with sealant per capita increased by approximately 0.4 to 0.8 (P < 0.001). The proportion of individuals with decay-missing-filled permanent teeth decreased by 9.1% (from 68.4 to 59.3, P < 0.001), and the average decay-missing-filled permanent teeth index per person decreased by approximately 2.0 to 1.5 (P < 0.001). The rate of single-crown holders decreased by 2.7% (from 8.7 to 6.0, P > 0.05), and the average single-crown index decreased by approximately 0.11 to 0.08 per person(P > 0.05). The number of sealants increased with age and household income (P < 0.001). The mother's education level affected sealant experience (P < 0.05). The caries rate was higher in females and older respondents (P < 0.001). CONCLUSIONS: The sealant covered by NHIS contributed to decreasing dental caries in Korea. However, policies that can reduce oral health inequality should also be considered, and a follow-up study is required for long-term sealant maintenance in Korea.

Using a Mobile-based Nutritional Intervention Application Improves Glycemic Control but Reduces the Intake of Some Nutrients in Patients with Gestational Diabetes Mellitus: A Case Series Study.

The prevalence of gestational diabetes mellitus (GDM) has been increasing worldwide, as has the economic cost associated with this condition. GDM threatens the health of the mother and child, and thus proper monitoring and management are essential. Mobile healthcare services have been applied to manage some diseases, particularly chronic diseases. We aimed to evaluate the utility of a mobile application in nutritional intervention by observing cases of a mobile application in a series of patients with GDM. We provided a mobile-based intervention to GDM patients and collected biochemical and nutritional information. The mobile-based nutritional intervention was effective in controlling carbohydrate intake and improving blood glucose level for patients with GDM.

Renal transplantation in patients with an augmentation cystoplasty.

Background: The effects of renal transplantation in patients with augmentation cystoplasty are still controversial. We retrospectively analyzed nine patients who underwent renal transplantation after augmentation cystoplasty. Methods: A total of nine patients who underwent augmentation cystoplasty prior to renal transplantation between January 1990 and May 2020 were reviewed. Basic information on augmentation cystoplasty, transplant procedures, and long-term outcomes of renal transplantation were analyzed. Results: The bowel segments utilized for augmentation cystoplasty were the stomach in two patients (one patient needed revision using the ileum), the ileum in four patients, the ileocolic pouch in one patient, the sigmoid in one patient, and the ureter in one patient. All the cystoplasties were performed prior to renal transplantation. The mean follow-up period after transplantation was 161 months (range, 2-341 months). Two patients had an episode of acute rejection each; however, their graft functions were well-maintained. Five patients had recurrent urinary tract infections, and three of these patients progressed to allograft failure. One patient died from bladder cancer with a functioning graft. Five of nine patients showed well-maintained graft function. Conclusions: Renal transplantation after bladder augmentation surgery is a major operation requiring a high level of surgical skill. Based on our long-term experiences, we recommend diligent postoperative monitoring for urinary tract infections, optimal catheter use, and use of appropriate antibiotic prophylaxis to avoid severe complications.

The impact of national health insurance coverage on pit and fissure sealing experience.

INTRODUCTION: The purpose of this study was to review the change of supplied amount of oral pit and fissure sealing (PFS) in urban and rural areas of South Korea after including PFS into the list of treatments covered by the National Health Insurance (NHI), and to check whether there is a difference in supplied amount in areas where the dental treatment accessibility is different based on the data of the Korean National Health and Nutritional Examination Survey (KNHANES). METHODS: The KNHANES data year used for 'before coverage' was 2007, and that of 'after coverage' was 2012. Data analysis was done using STATA software. RESULTS: Areas were classified as urban or rural. Reduction of out-of-pocket expenses, according to the NHI coverage PFS experience of children aged 6-14 years, increased from 28.7% before coverage to 34.9% after coverage. PFS experience of children aged 6-14 years in the urban area was increased from 29.2% before coverage to 35.6% after coverage. The increase in rural areas was from 27.2% before coverage to 31.5% after coverage. CONCLUSIONS: Although PFS supplying was increased after inclusion in NHI coverage, it is still insufficient to reduce the decayed, missing, filled teeth index effectively. To reduce inequality, supply of PFS in rural area by community oral health program should be strengthened. And also, waiving out-of-pocket money for PFS in NHI should be considered.

Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XL.

In response to genotoxic stress, the tumor suppressor protein p73 induces apoptosis and cell cycle arrest. Despite extensive studies on p73-mediated apoptosis, little is known about the cytoplasmic apoptotic function of p73. Here, using H1299 lung cancer cells and diverse biochemical approaches, including colony formation, DNA fragmentation, GST pulldown, and apoptosis assays along with NMR spectroscopy, we show that p73 induces transcription-independent apoptosis via its transactivation domain (TAD) through a mitochondrial pathway and that this apoptosis is mediated by the interaction between p73-TAD and the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL or BCL2L1). This binding disrupted an interaction between Bcl-XL and the pro-apoptotic protein BH3-interacting domain death agonist (Bid). In particular, we found that a 16-mer p73-TAD peptide motif (p73-TAD16) mediates transcription-independent apoptosis, accompanied by cytochrome c release from the mitochondria, by interacting with Bcl-XL Interestingly, the structure of the Bcl-XL-p73-TAD16 peptide complex revealed a novel mechanism of Bcl-XL recognition by p73-TAD. We observed that the α-helical p73-TAD16 peptide binds to a noncanonical site in Bcl-XL, comprising the BH1, BH2, and BH3 domains in an orientation opposite to those of pro-apoptotic BH3 peptides. Taken together, our results indicate that the cytoplasmic apoptotic function of p73 is mediated through a noncanonical mode of Bcl-XL recognition. This finding sheds light on a critical transcription-independent, p73-mediated mechanism for apoptosis induction, which has potential implications for anticancer therapy.

Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability.

BACKGROUND: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. METHODS: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. RESULTS: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. CONCLUSIONS: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.

N-3 polyunsaturated fatty acids restore Th17 and Treg balance in collagen antibody-induced arthritis.

N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and were considered useful for the treatment of rheumatoid arthritis (RA). Recently, several studies suggested that n-3 PUFAs attenuated arthritis in animal model and human, however the mechanism is still unclear. Interleukin 17 (IL-17) is a pro-inflammatory cytokine mainly produced by T helper 17 (Th17) cells which cause tissue inflammation and bone erosion leading to joint destruction. In contrast, regulatory T (Treg) cells down-regulate various immune responses by suppression of naïve T cells. The imbalance between Th17 cells and Tregs cell is important for the pathogenesis of RA. Here, we investigated whether n-3 PUFAs attenuate arthritis in collagen antibody-induced arthritis (CAIA) model. We used fat-1 transgenic mice expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids, leading to abundant n-3 fatty acids without the need of a dietary n-3 supply. Clinical arthritis score was significantly attenuated in fat-1 mice compared to wild type (WT) mice on day 7 (1.6±1.8, p = 0.012) and day 9 (1.5±1.6, p = 0.003). Ankle thickness also decreased significantly in fat-1 mice compared to WT mice (1.82±0.11, p = 0.008). The pathologic finding showed that inflammatory cell infiltration and bone destruction were reduced in fat-1 mice compared to WT. The expression levels of IL-17 and related cytokines including IL-6 and IL-23 decreased in the spleen and ankle joint tissue of fat-1 mice compared to WT mice. Furthermore, Treg cells were expanded in the spleen of fat-1 mice and Treg cell differentiation was significantly higher in fat-1 mice than in wild type (p = 0.038). These data suggest that n-3 PUFAs could attenuate arthritis through increasing the expression of FoxP3 and the differentiation of Treg, while reducing IL-17 production. Therefore, dietary supplementation of n-3 PUFAs could have a therapeutic potential for the treatment of RA.

Association of meal frequency with metabolic syndrome in Korean adults: from the Korea National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Although previous studies have established a close relationship between caloric intake and metabolic syndrome, there is limited research exploring the impact of meal frequency adjusted by caloric intake on metabolic syndrome (MetS). OBJECTIVE: To evaluate the association of meal frequency and MetS after adjusting for confounding factors including caloric intake in Korean men and women. METHODS: We analyzed the national representative data of a total 12,389 adults (5171 men, 7218 women) from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012. Subjects were categorized as eating 3 meals/day (MF3) or 2 or fewer meals/day (MF ≤ 2). Daily caloric intake was calculated using CAN-Pro 4.0 (The Korean Nutrition Society, Seoul, Korea). RESULTS: The prevalence of components of MetS differed significantly according to meal frequency in both men and women. In an unadjusted analysis, the prevalence of MetS in women was significantly higher in the MF3 group than the MF ≤ 2 group (27.5% vs. 17.8%, P < 0.001), whereas the prevalence of MetS in men did not differ between the MF3 and MF ≤ 2 groups (24.6% vs. 22.7%, P = 0.281). However, after adjusting for age, caloric intake, smoking status, alcohol consumption, physical activity, income, and education level, men in the MF ≤ 2 group had an increased risk of metabolic syndrome compared to men in the MF3 group (OR = 1.37, 95%, CI = 1.12-1.67). On the other hand, meal frequency did not affect the risk of metabolic syndrome in women after adjusting for confounding factors including caloric intake (OR = 1.09, 95%, CI = 0.90-1.31). CONCLUSIONS: This study suggests that lower meal frequency adjusted for caloric intake, physical activity, age, smoking, alcohol, income, and education may be associated with increased risk of MetS in Korean men.

cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.

Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H2O2 induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation.

Skeletal overgrowth syndrome caused by overexpression of C-type natriuretic peptide in a girl with balanced chromosomal translocation, t(1;2)(q41;q37.1).

Chromosomal translocation of 2q37.1 just distal to the NPPC gene coding for C-type natriuretic peptide (CNP) and subsequent overproduction of CNP have been reported to cause a skeletal overgrowth syndrome. Loeys-Dietz syndrome (LDS) is one of marfanoid overgrowth syndromes, of which subtype IV is caused by haploinsufficiency of transforming growth factor beta 2 (TGFB2). We report on a girl with clinical phenotypes of overgrowth syndrome, including long and slim body habitus, macrodactyly of the big toe, scoliosis, ankle valgus deformity, coxa valga, slipped capital femoral epiphysis, and aortic root dilatation. Karyotyping revealed a balanced chromosomal translocation between 1q41 and 2q37.1, and the breakpoints could be mapped by targeted resequencing analysis. On chromosome 2q37.1, the translocation took place 200,365 bp downstream of NPPC, and serum level of the amino terminal of CNP was elevated. The contralateral site of translocation on chromosome 1q41 disrupted TGFB2 gene, presumed to cause its haploinsufficiency. This case supports the concept that NPPC is overexpressed because of the loss of a specific negative regulatory control in the normal chromosomal location, and demonstrates the effectiveness of targeted resequencing in the mapping of breakpoints.