Genotype correlates with the natural history of severe bile salt export pump deficiency Highlights NAPPED is the largest global database of genotyped patients with BSEP deficiency. The genotype of patients with BSEP deficiency predicts survival with native liver. Genotype predicts long-term benefit of interruption of enterohepatic circulation. Serum bile acids can be a surrogate marker for long-term outcome. Treatment of patients with BSEP deficiency should be based on genotype.

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WHAT'S KNOWN ON THIS SUBJECT: Corrosive substance ingestion is a public health issue in developing countries. Stricture formation is a late complication of corrosive substance ingestion. The role of corticosteroids in preventing corrosiveinduced strictures is controversial.WHAT THIS STUDY ADDS: High doses of methylprednisolone therapy lead to less frequent stricture formation in grade IIb esophageal burns in children who ingested caustic substances and may improve prognosis. abstract OBJECTIVE: Caustic substance ingestion in childhood is a public health issue in developing countries, and several management protocols have been proposed to prevent the resulting esophageal strictures. The role of corticosteroids in preventing corrosive-induced strictures is controversial. Our aim was to study the influence of high doses of corticosteroids in preventing esophageal strictures. METHODS:Eighty-three children with a mean age of 4.10 6 2.63 years and with grade IIb esophageal burns (an esophagogastroscopy was performed within 24-48 hours of injury) due to corrosive substance ingestion were enrolled in our study between 2005 and 2008. Fortytwo children (study group) received methylprednisolone (1 g/1.73 m 2 per day for 3 days), ranitidine, ceftriaxone, and total parenteral nutrition. Forty-one children (control group) were administered the same regimen excluding methylprednisolone. Stricture development was compared between groups based on endoscopic and radiologic findings.

Objective:Considering the ever increasing population of diabetic adolescents and the association of the disease with psychosocial problems throughout its course, depression and/or anxiety and social support from parents are issues of special concern in these patients. The study aimed to identify the depression and anxiety state of diabetic adolescents and its impact on the management of diabetes mellitus (DM).Methods:295 adolescents with type 1 DM and their parents attended our study. Psychological distress was assessed using the Children’s Depression Inventory and the State-Trait Anxiety Inventory (STAI I-II) for Children, Perceived Social Support from Family (PSS-Fa) scale, Beck Depression Inventory for adults, STAI I-II for adults and the Multidimensional Scale of Perceived Social Support (MSPSS). Records of glycemic measurements, insulin dosage and hemoglobin A1c levels were used as glycemic control parameters. Results:Depression rate was 12.9%. State (p<0.001) and trait anxiety (p<0.001) levels were high; PSS-Fa (p<0.001) and MSPSS (p<0.006) scores were low in the depressive patients. Positive correlations were noted between depression, PSS-Fa, STAI-I and STAI-II.Conclusion:Therapeutic strategies of DM should include co-existing psychiatric conditions throughout the course of the disease. In diabetic adolescents, PSS-Fa, STAI-I and STAI-II appear to be effective tools in the evaluation of depression.

The capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is an autosomal recessive inborn error of immunity (IEI) leading to combined T-cell, B-cell, and NK cell defects. 1,2 CARMIL2, also known as RGD motif, leucine-rich repeats, tropomodulin domain, and proline-rich containing protein (RLTPR), is a member of the CARMIL family. This family consists of three paralogous genes (CARMIL1, CARMIL2, and CARMIL3), producing multidomain proteins with high sequence homology. They contain an N-terminal pleckstrin homology (PH) domain, a leucine-rich repeat (LRR) domain, a homodimerization domain (HD), and a C-terminal domain including a capping protein binding region (CBR) and a proline-rich region (PRR).While all CARMILs have a capacity to bind to the capping proteins and regulate actin assembly, each protein also has a unique cellular function. 3 CARMIL1 activates the Trio-Rac1 pathway to enhance Arp2/3-mediated actin polymerization, 4,5 whereas CARMIL2 binds to cellular membranes via vimentin, and activates T cells by ligating CD28 and CARMA1 to mediate NFk B signaling. 6,7 Mice expressing mutated Carmil2 gene are not able to conduct CD28-mediated activation of its effector protein kinase C theta (PKCθ), abrogating effector memory CD4 + T and regulatory T cells (Treg) development. 7,8 CARMIL2 is also necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, macropinocytosis, and cell migration. 3 The CARMIL3 is expressed mainly in the brain and spinal cord, and identified as oncofetal gene; however, recently, it was demonstrated as essential regulator of the proinflammatory cytokines in macrophages. 3,9 The human CARMIL2 gene was originally identified by Matsuzaka et al. and shown to be downregulated in affected skin cells of psoriasis vulgaris patients. 10 The CARMIL2 protein is expressed in the cytoplasm, especially in the skin, lymphoid tissue, and gastrointestinal system, and was demonstrated to play a role in wound healing. 3 So far, fewer than 40 cases of CARMIL2 deficiency have been reported worldwide. Patients with CARMIL2 deficiency present with a broad range of symptoms, including cutaneous and respiratory allergies mainly characterized by eczematous lesions, early-onset