Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease affecting extremely preterm infants. While mitochondrial dysfunction has been investigated in various medical conditions, limited research has explored mitochondrial DNA (mtDNA) gene mutations, specifically in BPD. This study aimed to evaluate mitochondrial mtDNA gene mutations in extremely preterm infants with BPD. In this prospective observational study, we enrolled a cohort of extremely preterm infants diagnosed with BPD. Clinical data were collected to provide comprehensive patient profiles. Peripheral blood mononuclear cells were isolated from whole-blood samples obtained within a defined timeframe. Subsequently, mtDNA extraction and sequencing using next-generation sequencing technology were performed to identify mtDNA gene mutations. Among the cohort of ten extremely preterm infants with BPD, mtDNA sequencing revealed the presence of mutations in seven patients, resulting in a total of twenty-one point mutations. Notably, many of these mutations were identified in loci associated with critical components of the respiratory chain complexes, vital for proper mitochondrial function and cellular energy production. This pilot study provides evidence of mtDNA point mutations in a subset of extremely preterm infants with BPD. These findings suggest a potential association between mitochondrial dysfunction and the pathogenesis of BPD. Further extensive investigations are warranted to unravel the mechanisms underlying mtDNA mutations in BPD.

Outcomes at 18-24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013-2017: A Nationwide Cohort Study.

INTRODUCTION: This study aimed to investigate the outcomes of infants at 18-24 months born in the Korean Neonatal Network with a birth weight <500 g. METHODS: The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013-2017 and followed up at a corrected age of 18-24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician's referral to developmental specialists. RESULTS: At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. CONCLUSION: Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18-24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.

Wide-wavelength-tunable distributed Bragg reflector laser diode with high thermal efficiency.

We proposed a thermally-tuned distributed Bragg reflector (DBR) laser diode that has a high tuning efficiency over a wide wavelength tuning range. The laser diode is composed of a gain, a phase control (PC), and a DBR region, and its wavelength is tuned coarsely and finely by the micro-heaters on the DBR and PC regions, respectively. To improve the tuning efficiency, we developed a technique for fabricating a thermal isolation structure through a reverse mesa etching process, replacing the complex process that uses an InGaAs sacrificial layer. The DBR laser diodes (DBR-LD) fabricated using this method effectively confines heat generated by the heater, resulting in an approximate tuning range of 40 nm. This technology, which has achieved nearly four times larger wavelength tuning range than the thermally-tuned DBR-LDs without a thermal isolation structure, is considered suitable for the cost-effective development of wide-wavelength-tuning DBR-LD light sources.

Prevention of human milk-acquired cytomegalovirus infection in very-low-birth-weight infants.

BACKGROUND: The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods. METHODS: A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother's own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks. RESULTS: Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group. CONCLUSIONS: HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection.

Wearable Surface-Lighting Micro-Light-Emitting Diode Patch for Melanogenesis Inhibition.

Wearable light-emitting diode (LED)-based phototherapeutic devices have recently attracted attention as skin care tools for wrinkles, acne, and hyperpigmentation. However, the therapeutic effectiveness and safety of LED stimulators are still controversial due to their inefficient light transfer, high heat generation, and non-uniform spot irradiation. Here, a wearable surface-lighting micro-LED (SµLED) photostimulator is reported for skin care and cosmetic applications. The SµLEDs, consisting of a light diffusion layer (LDL), 900 thin film µLEDs, and polydimethylsiloxane (PDMS), achieve uniform surface-lighting in 2 × 2 cm2 -sized area with 100% emission yields. The SµLEDs maximize photostimulation effectiveness on the skin surface by uniform irradiation, high flexibility, and thermal stability. The SµLED's effect on melanogenesis inhibition is evaluated via in vitro and in vivo experiments to human skin equivalents (HSEs) and mouse dorsal skin, respectively. The anti-melanogenic effect of SµLEDs is confirmed by significantly reduced levels of melanin contents, melan-A, tyrosinase, and microphthalmia-associated transcription factor (MITF), compared to a conventional LED (CLED) stimulator.

Hair methylmercury levels are inversely correlated with arterial stiffness.

BACKGROUND AND AIMS: Cardiovascular diseases (CVD), including coronary heart disease, are the leading cause of death worldwide. Several studies investigating the relationship between fish intake, methylmercury exposure, and CVDs in adults have reported inconsistent results. This study aimed to determine the association between hair methylmercury levels and arterial stiffness using brachial-ankle pulse wave velocity (baPWV). METHODS: This cross-sectional study included 891 seemingly healthy Korean adults (418 men and 473 women). The anthropometric and biochemical profiles, including methylmercury levels in the hair, were measured. Arterial stiffness was measured using baPWV, wherein high baPWV was defined as >1375 cm/s (>75th percentile). The odds ratios for high baPWVs were examined using multivariable logistic regression analysis after adjusting for potential confounders across the quintiles of hair methylmercury levels (Q1 = ≤0.6, Q2 = 0.6-0.8, Q3 = 0.8-1.1, Q4 = 1.1-1.5, and Q5=>1.5 µg/g). RESULTS: After adjusting for multiple confounders-age, sex, height, body weight, smoking status, weekly alcohol consumption, total metabolic equivalent of task, mean arterial blood pressure, resting heart rate, triglycerides, low density lipoprotein cholesterol, fasting plasma glucose, uric acid and white blood cell count-the odds ratios (95% confidence intervals) for high baPWVs in each quintile of hair methylmercury levels were 1.00, 0.36 (0.17-0.76), 0.38 (0.20-0.76), 0.28 (0.13-0.61), and 0.49 (0.24-0.99), respectively. CONCLUSIONS: Within non-toxic low levels, higher hair methylmercury levels are independently associated with lower arterial stiffness in seemingly healthy Korean adults regardless of classical cardiovascular risk factors.

Neonatal sepsis-causing bacterial pathogens and outcome of trends of their antimicrobial susceptibility a 20-year period at a neonatal intensive care unit.

BACKGROUND: Due to increases in the number of infants born with younger gestational age (GA) and lower birth weight, the incidence of neonatal sepsis is increasing. PURPOSE: We investigated the changes in the prevalence of bacterial pathogens, their antimicrobial susceptibility, and sepsis-related mortality during 20 years at a neonatal intensive care unit. METHODS: The study period was divided into two 10-year phases (1998-2007 vs. 2008-2017). Medical records were reviewed to gather data on demographics, causative microbial pathogens, incidence of multidrug-resistant organisms, antimicrobial susceptibility, and rates of sepsis-related mortality. RESULTS: In both study phases, the most common pathogens for neonatal sepsis were coagulase-negative Staphylococcus (CoNS) (28.6%) and Enterobacter cloacae (16.1%) for early-onset sepsis (EOS, ≤72 hours after birth) and CoNS (54.7%) and Staphylococcus aureus (12.9%) for late-onset sepsis (LOS, >72 hours after birth). CoNS and S. aureus showed 100% sensitivity to vancomycin in both phases. The susceptibility of S. aureus to oxacillin increased from 19.2% to 57.9% in phase II than phase I. K. pneumonia and E. cloacae showed increases in its susceptibility to gentamicin, cefotaxime and ceftriaxone in phase II than phase I. In both phases, the most common pathogens that caused sepsis-related death were K. pneumoniae (18.2%) and Pseudomonas aeruginosa (13.6%). Sepsis-related mortality rate was higher in infants with GA <37 weeks than those with GA over 37 weeks (P=0.016). In addition, the mortality rate of neonatal sepsis caused by gram-negative bacteria was significantly higher than that caused by gram-positive bacteria (P<0.001). CONCLUSIONS: CoNS was the most common pathogen for EOS and LOS. While we found significant changes in antimicrobial sensitivities over time. GA below 37 weeks and gram-negative organisms are associated with mortality rate.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Survival and Morbidities in Infants with Birth Weight Less than 500 g: a Nationwide Cohort Study.

BACKGROUND: This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. METHODS: The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. RESULTS: The survival rate of the infants was 28%, with a median gestational age and BW of 243/7 weeks (range, 220/7-336/7) and 440 g (range, 220-499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400-499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups. Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III-IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69-291), and 53% required assistive devices at discharge. CONCLUSION: Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.

Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial.

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 107 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957.

Functional and structural evaluation in the lungs of children with repaired congenital diaphragmatic hernia.

BACKGROUND: To evaluate the long-term functional and structural pulmonary development in children with repaired congenital diaphragmatic hernia (CDH) and to identify the associated perinatal-neonatal risk factors. METHODS: Children with repaired CDH through corrective surgery who were born at gestational age ≥ 35 weeks were included in this analysis. Those who were followed for at least 5 years were subjected to spirometry and chest computed tomography for evaluation of their functional and structural growth. Main bronchus diameters and lung volumes (total, left/right) were measured. According to total lung volume (TLV) relative to body surface area, children were grouped into TLV ≥ 50 group and TLV < 50 group and the associations with perinatal-neonatal factors were analyzed. RESULTS: Of the 28 children (mean age, 6.2 ± 0.2 years) with left-sided CDH, 7 (25%) had abnormal pulmonary function, of whom 6 (87%) showed restrictive patterns. All pulmonary functions except FEF25-75% were worse than those in matched healthy control group. Worse pulmonary function was significantly associated with small head and abdominal circumferences at birth. The mean TLV was 1339.1 ± 363.9 mL and LLV/TLV was 47.9 ± 2.5 mL. Children with abnormal pulmonary function were more likely to have smaller lung volumes. In multivariate analysis, abdominal circumference at birth was significantly associated with abnormal lung volume. CONCLUSIONS: A quarter of children with repaired CDH showed abnormal pulmonary function. Small abdominal circumference at birth was associated with abnormal pulmonary function and lower TLV. .

16-channel tunable and 25-Gb/s EAM-integrated DBR-LD for WDM-based mobile front-haul networks.

We report a tunable distributed Bragg reflector-laser diode (DBR-LD) integrated with an electro-absorption-modulator (EAM) at an operating wavelength of 1.3 µm. This LD consists of gain, phase control (PC), DBR, and EAM sections, realized by using a butt-coupling technique in monolithically integrating the multiple quantum wells (MQWs) with the passive core and by applying an etched-mesa buried hetero-structure (EMBH) to the resonance cavity (i.e., gain to DBR section) and a deep-ridge type to the EAM section in fabricating the waveguide structure. Wavelength tuning of the LD is achieved by both applying a voltage to the heater metal of DBR section (coarse tuning) and injecting a current to the ohmic metal of PC section (fine tuning). From the work, the fabricated chips show a threshold current of about 13 mA, a side mode suppression ratio (SMSR) of more than 35 dB, and a tuning range of 15 nm within a heater voltage of 2 V. Dynamic tests for the EAM-integrated LD show the 3 dB bandwidth of more than 20 GHz and clear 25 Gb/s eye openings with a dynamic extinction ratio (DER) of over 7 dB for 16 channels spaced at the wavelength interval of 0.55 nm. Based on these results, we conclude that the EAM-integrated DBR-LD is capable of providing 16 channel operation at a data rate of 25 Gb/s and can be used as an effective light source for WDM-based mobile front-haul networks.

Comparing Axillary and Rectal Temperature Measurements in Very Preterm Infants: A Prospective Observational Study.

PURPOSE: The agreement between axillary temperature (AT) and rectal temperature (RT) measurements has not been well established in preterm infants. Therefore, our study aimed to evaluate the agreement between AT and RT measurements in very preterm infants. METHODS: Preterm infants <32 weeks of gestational age were prospectively included. The infants' body temperature (BT) was measured twice a day from day 1 to day 6. A paired t-test and the Bland-Altman method were used to analyze the difference between the AT and RT. A linear regression model was used to explore the effects of environmental factors on the differences of BT between the axillary and rectal measurements and to calibrate the RT according to the AT. RESULTS: Eighty infants each underwent 6 paired axillary and rectal measurements. The gestational age varied from 22 to 31 weeks (mean 28 weeks). The birth weight varied from 302 to 1,770 g (mean 1,025 g). The AT was significantly lower than the RT. The difference between the RT and AT significantly increased with increasing RT. The AT and RT demonstrated poor agreement overall; however, the RT can be estimated using the AT with the following equation: RT = -4.033 + 1.116 × AT. Environmental factors, including the incubator temperature, incubator humidity, phototherapy, and application of invasive mechanical ventilation did not affect the differences between the AT and RT measurements. CONCLUSION: AT measurements cannot be interchangeably used with RT measurements in very preterm infants.

Extremely low birth weight infant surviving left congenital diaphragmatic hernia: a case report.

In this study, we present the case of a 900 g, male infant born at 27+5 weeks, who was placed on high frequency oscillatory ventilation (HFOV) until repair of a left congenital diaphragmatic hernia (CDH) at 39 days of life (DOL). To date, this is the smallest infant with repair of the left CDH reported in the literature. After birth, he passed the cardiopulmonary stabilization phase and successfully underwent delayed surgery; in the process, he received ventilator assistance through HFOV. He weighed 1,660 gm at the time of surgery. We performed the thoracoscopic primary closure of the diaphragmatic defect. He was extubated on post-operation day (POD) 7 and discharged from hospital on POD 36 with 0.1 L/min supplemental oxygen via nasal cannula. He is being followed for growth and development and there has been no recurrence at the surgical site at 24 months of corrected age. In this case, high mean airway pressure (MAP) was required based on the patient's weight to achieve adequate recruitment of the left lung, and the patient was diagnosed with mental developmental delay on Bayley Scales of Infant Development-II. Thus, we suggest that the postnatal course and long-term outcomes for extremely low birth weight (ELBW) and preterm infants with left CDH is different from that for full-term babies. Therefore, future research should focus on preterm infants with left CDH.

Morbidity and Mortality of Very Low Birth Weight Infants with Congenital Heart Disease.

BACKGROUND AND OBJECTIVES: This study aimed to provide morbidity and mortality information on very low birth weight (VLBW) infants with congenital heart disease (CHD-VLBWs). METHODS: The study used a 10-year cohort of VLBW infants from a single institution. CHD was classified according to International Classification of Diseases, Version 9, Clinical Modification. Mortality and neonatal outcomes were assessed by comparing the CHD-VLBWs with gestational age- and birth weight-matched controls. RESULTS: The prevalence of CHD-VLBWs was 7.5% (79/1,050), mean gestational age was 31.1±3.2 weeks, and mean birth weight was 1,126.2±268.3 g; 50.6% of the infants were small for the gestational age. The CHD-VLBWs more commonly had bronchopulmonary dysplasia (BPD), and the longer they were exposed to oxygen, the more frequently they developed BPD. Those with cyanotic heart disease developed severe BPD more frequently. Necrotizing enterocolitis (NEC) occurred frequently in the CHD-VLBWs and was not associated with their feeding patterns. CHD-VLBWs had a higher mortality rate; prematurity-related diseases were the leading cause of death before surgery, while heart-related problems were the leading cause of death after surgery. We found no significant difference in mortality from prematurity-related disease between the CHD-VLBWs and controls. In the subgroup analysis of CHD, the cyanotic CHD group had a higher incidence of BPD and higher mortality rate than the acyanotic CHD group. CONCLUSIONS: CHD-VLBWs showed higher BPD, NEC, and mortality rates than those without CHD. There was also a higher incidence of BPD and mortality in VLBW infants with cyanotic CHD than in those with acyanotic CHD.

Challenges of acute peritoneal dialysis in extremely-low-birth-weight infants: a retrospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) has been used occasionally in extremely-low-birth-weight (ELBW) infants with acute kidney injury (AKI). This study aimed to evaluate the clinical characteristics and outcomes of ELBW infants with AKI treated with PD. METHODS: In this retrospective cohort study, the medical records of ELBW infants with AKI, who underwent PD from January 2008 to February 2018, were reviewed. A PD catheter (7.5-9.0 Fr) or central venous catheter (4 Fr) was used for the peritoneal access. Treatment with PD solutions (2.5 or 4.25%) was started at 10 mL/kg, which was increased to 20-30 mL/kg for 60-120 min/cycle continuing for 24 h. RESULTS: Twelve ELBW infants (seven male and five female infants) were treated, and their mean (±SD) gestational age and birth weight were 27.2 (±3.3) weeks and 706.5 (±220.5) g, respectively. Two patients had severe perinatal asphyxia (5-min Apgar score ≤ 3). The most important indication for starting PD was AKI due to sepsis. The average (±SD) duration of PD was 9.4 (± 7.7) days. The potassium levels in the ELBW infants with hyperkalemia decreased from 6.8 to 5.0 mg/mL after 9.3 (± 4.4) days. The most common complication of PD was mechanical dysfunction of the catheters, such as dialysate leakage (75%). Two patients were successful weaned off PD. The mortality rate of the infants treated with PD was 91.7%. CONCLUSIONS: In this series, the mortality rate of ELBW infants with AKI treated with PD was relatively high because of their incompletely developed organ systems. Therefore, the use of PD should be carefully considered for the treatment of ELBW infants with AKI in terms of decisions regarding resuscitation.

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus.

Plasma B-type natriuretic peptide (BNP) is a useful marker for diagnosis of hemodynamically significant PDA (hsPDA) and serial BNP measurement is also valuable for monitoring treatment response. This retrospective study was performed to evaluate whether plasma BNP level can predict treatment response to ibuprofen in preterm infants born at <30 weeks of gestation with hsPDA. Plasma BNP was measured before (baseline) and 12 to 24 h after (post-treatment) completion of the first (IBU1) and second (IBU2) course of ibuprofen. We compared the BNP levels of responders (closed or insignificant PDA) with those of non-responders (hsPDA requiring further pharmacologic or surgical closure) to each course of ibuprofen. The treatment response rates for IBU1 (n = 92) and IBU2 (n = 19) were 74% and 26%, respectively. In IBU1, non-responders had lower gestational age and birth weight than responders (both, P = 0.004), while in IBU2, non-responders had lower birth weight (P = 0.014) and platelet counts (P = 0.005) than responders; however, baseline BNP levels did not differ significantly between responders and non-responders in either IBU1 (median 1,434 vs. 1,750 pg/mL) or IBU2 (415 vs. 596 pg/mL). Post-treatment BNP was a useful marker for monitoring treatment efficacy of IBU1 and IBU2 for hsPDA with a cut-off value of 331 pg/mL (P < 0.001) and 423 pg/mL(P < 0.010), respectively. We did not identify a cut-off baseline BNP level that could predict treatment response to ibuprofen in preterm infants with hsPDA.

Neonatal exchange transfusion: Experience in Korea.

BACKGROUND: Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea. MATERIALS AND METHODS: We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET. RESULTS: The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation. CONCLUSIONS: ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

1.3-µm and 10-Gbps tunable DBR-LD for low-cost application of WDM-based mobile front haul networks.

We report a 1.3-µm and 10-Gbps tunable distributed Bragg reflector laser diode (DBR-LD) for the low-cost application of a wavelength division multiplex based mobile front-haul network. The device consists of gain, phase control, and DBR sections, implemented using a butt-coupling method through a monolithic integration and through the introduction of an etched mesa planar buried hetero-structure in a waveguide structure. From the work, a 560-µm long DBR-LD with a 220-µm long micro-heater DBR section has a threshold current of 10 mA ± 1 mA and a tuning range of more than 15 nm within a heater injection current of ∼100 mA. Spectral and dynamic tests for this LD show 16 channels spaced a wavelength grid of 0.8 nm with a side mode suppression ratio of greater 40 dB and clear eye openings with a dynamic extinction ratio of over 5.4 dB at an operating current of 60 mA.

4-O-methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK-mediated cardiac lipid metabolism improvement.

Diabetic cardiomyopathy (DCM) is characterized by increased left ventricular mass and wall thickness, decreased systolic function, reduced ejection fraction (EF) and ultimately heart failure. The 4-O-methylhonokiol (MH) has been isolated mainly from the bark of the root and stem of Magnolia species. In this study, we aimed to elucidate whether MH can effectively prevent DCM in type 2 diabetic (T2D) mice and, if so, whether the protective response of MH is associated with its activation of AMPK-mediated inhibition of lipid accumulation and inflammation. A total number of 40 mice were divided into four groups: Ctrl, Ctrl + MH, T2D, T2D + MH. Five mice from each group were sacrificed after 3-month MH treatment. The remaining animals in each group were kept for additional 3 months without further MH treatment. In T2D mice, the typical DCM symptoms were induced as expected, reflected by decreased ejection fraction and lipotoxic effects inducing lipid accumulation, oxidative stress, inflammatory reactions, and final fibrosis. However, these typical DCM changes were significantly prevented by the MH treatment immediately or 3 months after the 3-month MH treatment, suggesting MH-induced cardiac protection from T2D had a memory effect. Mechanistically, MH cardiac protection from DCM may be associated with its lipid metabolism improvement by the activation of AMPK/CPT1-mediated fatty acid oxidation. In addition, the MH treatment of DCM mice significantly improved their insulin resistance levels by activation of GSK-3ß. These results indicate that the treatment of T2D with MH effectively prevents DCM probably via AMPK-dependent improvement of the lipid metabolism.