In Situ Regeneration of Si-based ARROW-B Surface Plasmon Resonance Biosensors

Si-based antiresonant reflecting optical waveguide type B (ARROW-B) surface plasmon resonance (SPR) biosensors allow label-free high-sensitivity detection of biomolecular interactions in real time. The ARROW-B waveguide, which has a thick guiding layer, provides efficient coupling with a single-mode fiber. The Si-based ARROW-B SPR biosensors were fabricated by using the standard semiconductor fabrication processes with a single-step lithography. A fluid flow system was designed to transport samples or analytes. The waveguide consists of propagation and SPR sensing regions. The propagation regions in the front and rear of the SPR sensing region have a symmetric cladding structure to isolate them from environmental changes. A high-index O-ring is used to seal the liquid flow channel. The intensity interrogation method was used to characterize the sensors. The sensitivity of the biosensors was 3.0 × 10(3) µW/RIU (refractive index unit) with a resolution of 6.2 × 10(−5) RIU. An in situ regeneration process was designed to make the sensors reusable and eliminate re-alignment of the optical measurement system. The regeneration was realized using ammonia-hydrogen peroxide mixture solutions to remove molecules bound on the sensor surface, such as self-assembled 11-mercapto-1undecanoic acid and bovine serum albumin. SPR was used to monitor the regeneration processes. The experimental results show that the sensing response did not significantly change after the sensor was reused more than 10 times. In situ regenerations of the sensors were achieved

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Serum retinol levels and neonatal outcomes in preterm infants

Glucocorticoids are frequently administered to preterm infants, both antenatally and postnatally; however, the effect on serum retinol levels has not been determined. The risk of bronchopulmonary dysplasia is increased in premature infants with low retinol concentrations. Objectives: Our purpose was to determine the effect of glucocorticoid administration on serum retinol levels in preterm infants. Methods: All infants <1250 g or <29 weeks' gestation admitted to the neonatal intensive care unit within 48 h of birth were eligible for inclusion. A retinol concentration <20 μg/dL during the first 48 h of birth was defined as low serum retinol, and a level <10 μg/dL as retinol deficiency. Results: Data from 115 premature infants were collected during a 7-year period, from 2005 to 2012. Neither antenatal nor postnatal steroid administration affected retinol concentrations. Retinol deficiency was associated with an increased risk for severe respiratory distress syndrome and adverse pulmonary outcome (death during the first 28 days of life and long-term oxygen dependence >90 days); low retinol levels conferred an increased risk for bronchopulmonary dysplasia. Prolonged duration of total parenteral nutrition (>21 days) was associated with serum retinol deficiency during hospitalization (P < 0.05). Retinol deficiency was associated with an increased risk for delayed neurological development in 1-year-old and 2-year-old children. Conclusion: Glucocorticoids do not affect retinol levels in premature infants, but retinol concentrations are correlated with respiratory and neurological outcomes

Neurodevelopmental outcomes at 2 and 5 years of age in very-low-birth-weight preterm infants born between 2002 and 2009: A prospective cohort study in Taiwan

Background: Neurodevelopmental outcome in preterm infants has been of great importance in recent decades. We determined the prevalence of abnormal neurodevelopmental outcomes and associated risk factors of very-low-birth-weight (VLBW) preterm infants at 2 and 5 years of age. Methods: We conducted a population-based, prospective cohort study of VLBW preterm infants born between 2002 and 2009 in Taiwan. Sociodemographic, neonatal data, and neurological assessments at 2 and 5 years of age were obtained from the database of Taiwan Premature Infant Follow-up Network. Results: Of the 6549 VLBW preterm infants included in the study, 5407 (82.56%) survived to discharge; 4105 and 1427 participated in follow-up assessments at age 2 and 5 years, respectively. At age 5 years, 76.87% (1097/1427), 12.05% (172/1427), and 8.76% (125/1427) of children had normal, borderline, and abnormal neurocognitive outcomes, separately. Among the enrolled children, 1385 were followed at both 2-year and 5-year-old. Among the 233 children with abnormal neurodevelopmental outcomes at age 5 years, nearly one-fifth (18.03%, 42/233) had normal or borderline neurodevelopmental outcomes at age 2 years. Among the 154 children with borderline neurodevelopmental outcomes at age 5 years, 71.43% (110/154) had normal or borderline neurodevelopmental outcomes at age 2 years. The risk factors significantly associated with disadvantageous (worsening or remaining unimproved) neurodevelopmental outcomes were lower gestational age, cystic periventricular leukomalacia, and paternal or maternal education ≤12 years. Conclusion: Almost one-fifth of VLBW preterm children with abnormal neurodevelopmental outcomes at age 5 years had normal or borderline neurologic and developmental assessments at age 2 years. For the high risk group such as VLBW preterm children, serial follow-up assessments beyond 2 years of age may be warranted and the eligibility of early intervention service should be revised by the government so proper and targeted intervention can be implemented at earlier age. Key Words: children development, preterm infants, risk factors, very-low-birth-weight infan

Congenital Candidiasis

Congenital candidiasis presents with a variety of clinical features. We report two neonates with congenital candidiasis characterized by diffuse erythematous papules associated with pneumonia and respiratory distress. Candida pseudohyphae were identifiable in skin scrapings. Systemic cultures were negative, but urine and sputum cultures grew Candida albicans. After prompt systemic antifungal therapy, the infants were discharged from hospital with no overt complications. This report highlights the presence of characteristic skin lesions associated with candidal infection, occurring within 24 hours of birth. This is an important observation which could help in the early diagnosis of congenital candidal infection

Epidemiological and microbiological characteristics of culture-proven acute otitis media in Taiwanese children

Background/PurposeAcute otitis media (AOM) is one of the most common diseases in children. Here, we describe the epidemiological and microbiological characteristics of AOM in Taiwanese children over a 10-year period.MethodsWe retrospectively enrolled pediatric patients with culture-proven AOM who were treated at Mackay Memorial Hospital, Taipei between 1999–2008. The data include demographic characteristics, clinical history, and microbiological characteristics.ResultsSix hundred and fourteen patients were included. The male:female ratio was 1.4 (p<0.001). Greater than three-fourths of the patients (476 [77.5%]) were < 5 years of age, and most patients were 1–2 years of age. The most common isolated pathogen was Streptococcus pneumoniae (419 patients [68.2%]), followed by nontypeable Haemophilus influenzae (NTHi; 118 patients [19.2%]). The distributions of age, gender, use of tympanocentesis, history of previous AOM, and use of antibiotic between patients infected with the two pathogens were not significantly different. However, the number of patients with AOM caused by S. pneumoniae, but not NTHi, decreased during the study period (p=0.004). Three hundred and eighty-seven children (63.0%) with AOM developed spontaneous otorrhea. Compared with patients who underwent tympanocentesis, those with spontaneous otorrhea were younger (27.0±16.4 vs. 31.1±15.2 months of age, p=0.004), more likely to have a previous history of AOM (p=0.019), and more likely to receive more antibiotics (p=0.012). The third most common pathogen was S. pyogenes (25 patients [4.1%]). S. pyogenes occurred more often in children > 5 years of age and was associated with spontaneous otorrhea (p<0.001).ConclusionS. pneumoniae and NTHi are common causes of culture-confirmed AOM in Taiwanese children. Although S. pyogenes is not as common, it usually causes AOM in children > 5 years of age and is associated with spontaneous otorrhea

Outcomes and related factors in a cohort of infants born in Taiwan over a period of five years (2007–2011) with borderline viability

Background: Advances in perinatal and neonatal care have increased the survival of extremely preterm infants, but the viability limit is still debated. Here we assess the survival, neonatal morbidity, and neurodevelopmental outcomes at 2 years of age of infants born at 22–26 weeks of gestation in Taiwan between 2007 and 2011. Methods: This is a prospective longitudinal multicenter cohort study on extremely preterm infants registered in the Taiwan Premature Infant Developmental Collaborative Study Group from 2007 to 2011, including 22 neonatal care centers. We extracted demographic and clinical data of infants born at 22–26 weeks, and obtained growth and developmental outcome data from the follow-up clinic at 24 months of corrected age. Multivariate analyses using a logistic regression model identified factors significantly impacting survival. Results: 647 of the 1098 infants included in the study (58.9%) survived to discharge. Survival rates were 8% (4/50), 25% (27/108), 46.8% (117/250), 67.0% (211/315), and 76.8% (288/375) for infants born at 22, 23, 24, 25, and 26 weeks, respectively. Most survivors (567/647, 87.6%) had major morbidities during hospitalization, and we identified factors that positively and negatively affected survival. 514 (79.4%) patients received follow-up evaluation at 2 years, and 204 (39.7%) of them had neurodevelopmental impairment (NDI) with an incidence of 75%, 65.2%, 49.5%, 39.5%, and 32.8% for infants born at 22, 23, 24, 25, and 26 weeks, respectively. Conclusion: Infants born at 22 and 23 weeks have a very low likelihood of surviving with little or no impairment. These findings are valuable for parental counseling and perinatal care decisions. Keywords: Extremely preterm, Morbidity, Mortality, Outcome