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Investigation of the chemical and electrical signals of cells in vivo is critical for studying functional connectivity and brain diseases. Most previous studies have observed either the electrical signals or the chemical signals of cells because recording electrical signals and neurochemicals are done by fundamentally different methods. Herein, we present a bimodal MEMS neural probe that is monolithically integrated with an array of microelectrodes for recording electrical activity, microfluidic channels for sampling extracellular fluid, and a microfluidic interface chip for multiple drug delivery and sample isolation from the localized region at the cellular level. In this work, we successfully demonstrated the functionality of our probe by monitoring and modulating bimodal (electrical and chemical) neural activities through the delivery of chemicals in a co-localized brain region in vivo. We expect our bimodal probe to provide opportunities for a variety of in-depth studies of brain functions as well as for the investigation of neural circuits related to brain diseases.

Key Clinical Message Chromosome 10p deletion is a rare disorder. This is the largest deletion in chromosome 10p reported to date and the first to be diagnosed in the early neonatal period because of severe clinical manifestations. This rare case might help to understand the genotype‐phenotype spectrum in infants with 10p deletion.

BACKGROUND Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B (FLNB) gene; however, several other genes can cause AO-like lethal skeletal dysplasias. METHODS In order to screen all possible genes associated with AO-like lethal skeletal dysplasias simultaneously, we performed whole-exome sequencing in a female newborn having clinical features of AO-I. RESULTS Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient's parents suggested a de novo occurrence of the variant. CONCLUSIONS This study shows that exome sequencing can be a useful tool for the identification of causative mutations in lethal skeletal dysplasia patients.

Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24-q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9)(p12q13),dup(15)(q24q26.3). Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea.

Background/Aims: This prospective study was conducted to investigate the feasibility of an early discontinuation of thyroid hormone treatment in very-low-birth-weight (VLBW) infants with congenital hypothyroidism (CH). Methods: We enrolled VLBW infants between January 2011 and December 2012. The infants were divided into the hypothyroid and normal thyroid function groups according to the results of a thyroid function test. We performed an early off-therapy trial at 24 months of age. Results: Of the 182 VLBW infants enrolled, 15 were lost to follow-up and 167 were finally enrolled. In total, 24 infants (14.4%) were assigned to the hypothyroid function group and were treated with thyroid hormone. Younger gestational age and a lower birth weight were associated with hypothyroid function. In the hypothyroid function group, hypothyroidism (HT) and hyperthyrotropinemia (HTT) were observed in 13 and 11 infants, respectively. There were no differences in the clinical characteristics between the HT and HTT groups. Overall, 24 infants discontinued thyroxine medication at 24 months of age after normal results had been confirmed by radiologic work-ups, including thyroid ultrasonography and technetium-99m scans. All infants were successfully weaned off thyroxine and maintained euthyroid function. Conclusion: Early discontinuation of thyroid hormone replacement therapy is possible in the majority of VLBW infants with CH.

Aim Parenteral nutrition (PN) provides an alternative nutrition source for preterm infants who are intolerant of enteral nutrition. However, prolonged PN increases the risk of PN-associated cholestasis (PNAC). We conducted this study to determine the incidence and risk factors of PNAC in extremely low birth weight (ELBW) infants. Methods We retrospectively reviewed the medical records of ELBW infants from March 2010 to April 2015. PNAC was diagnosed in infants with a history of PN for at least two weeks and direct bilirubin concentrations >2 mg/dL after other causes of neonatal cholestasis were excluded. Results Of the 114 eligible ELBW infants, 41 (36%) were diagnosed with PNAC. The multivariate analysis showed that birth weight, sepsis, necrotising enterocolitis, fluconazole prophylaxis and the duration of PN and hospitalisation were independent risk factors for the development of PNAC (p < 0.05). However, parenteral fish oil-based lipid preparation (FOLP) did not reduce the risk of PNAC. Although PNAC was not a direct cause of death, it was associated with an increased risk of mortality. Conclusion PNAC was common in ELBW infants, was associated with various clinical factors and increased the risk of mortality. However, we did not observe the protective effect of FOLP against PNAC.

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC (p.Pro22Argfs*2) and c.1090_1091delCT (p.Leu364Glufs*93). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.