Surgical necrotizing enterocolitis risk factors in extremely preterm infants: a Korean nationwide cohort study.

BACKGROUND: The incidence of necrotizing enterocolitis (NEC) is significantly associated with gestational age (GA). This study aimed to investigate risk factors for surgically treated NEC (sNEC) in extremely preterm infants (EPIs) using nationwide cohort registry. METHODS: Data were collected from 16,338 very-low-birth-weight infants registered in the Korean neonatal network. Clinical data of 5310 EPIs were retrospectively analyzed. sNEC was defined as infants with diagnosis of NEC requiring surgical treatment, who underwent surgical intervention for NEC or died before surgery. Infants were categorized into three groups based on their NEC status: infants without NEC (control), medically treated NEC (mNEC), and sNEC. These groups were matched based on GA to investigate risk factors for NEC. RESULTS: In EPIs, small for gestational age (SGA; odds ratio 1.68, 95% confidence interval [CI], 1.17-2.36, p = 0.004), hypotension (1.49, 1.18-1.89, p = 0.001), and IVH (1.63, 1.30-2.05, p < 0.001) were identified as risk factors for sNEC. Complete administration of antenatal steroid reduced the risk of sNEC (0.80, 0.64-0.99, p = 0.044). CONCLUSION: Our study demonstrated that EPIs who are SGA, and experience hypotension and IVH may be at an increased risk of developing NEC requiring surgery. These groups require close attention and monitoring for any signs of surgical indications of NEC. IMPACT: This nationwide cohort study aimed to identify characteristics of infants with necrotizing enterocolitis (NEC) among extremely preterm infants (EPIs) and analyze the risk factors associated with NEC requiring surgical intervention. Small for gestational age (SGA), hypotension, and intraventricular hemorrhage (IVH) were identified as significant risk factors for surgically treated NEC (sNEC) in EPIs. The administration of antenatal steroids decreases the risk of sNEC. Close attention and monitoring for EPIs with early identifiable risk factors such as SGA, hypotension, and IVH should be considered to prevent and detect sNEC early, ultimately leading to improved long-term outcomes.

Machine learning-based analysis for prediction of surgical necrotizing enterocolitis in very low birth weight infants using perinatal factors: a nationwide cohort study.

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction.    Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data.

Assessment of the Antioxidant and Anti-inflammatory Properties of Aqueous Extract of Rosa sempervirens Leaves.

The antioxidant and anti-inflammatory properties of an aqueous natural extract obtained from Rosa sempervirens leaves were assessed. The ability of the extract to scavenge DPPH, •OH, and H2O2 radicals, chelate ferrous ions, reduce ferric ions, and protect ß-carotene-linoleic acid in emulsion from peroxidation was investigated in vitro. Furthermore, the anti-inflammatory activity of the extract was evaluated by measuring the stability of the membrane of human red blood cells against different hypotonic concentrations of NaCl and heat, as well as by inhibiting the denaturation of albumin. A high total phenolic content (278.38± 11.07 mg GAE/g) and flavonoid content (34.22± 0.12 mg QE /g) were found in the extract. The extract exhibited significant scavenging activity of DPPH (IC50 6.201 ± 0.126 µg/ ml), •OH (IC50 = 894.57 ± 21.18 µg/ml), and H2O2 (IC50= 107±09.58 µg/ml) radicals, and good antioxidant activity by chelating ferrous ions (IC50 = 2499.086 ± 28.267µg/ml), reducing ferric ions (IC50=141.33±2.34 µg/ml), exhibiting total antioxidant capacity (IC50 465.65 ± 9.71 µg/ml), and protecting ß-carotene-linoleic acid against peroxidation (I% = 90.05 ± 1.65% at 1000µg/ml). R. sempervirens displayed anti-inflammatory activity in aqueous extract by inhibiting heat-induced albumin denaturation and stabilizing the membrane of human red blood cells. It was suggested from the results that R. sempervirens aqueous extract could help prevent oxidative and inflammatory processes due to its good antioxidant and anti-inflammatory properties.

A Review of Approaches to the Metallic and Non-Metallic Synthesis of Benzimidazole (BnZ) and Their Derivatives for Biological Efficacy.

Heterocyclic compounds are significant lead drug candidates based on their various structure-activity relationships (SAR), and their use in pharmaceutics is constantly developing. Benzimidazole (BnZ) is synthesized by a condensation reaction between benzene and imidazole. The BnZ structure consists of two nitrogen atoms embedded in a five-membered imide ring which is fused with a benzene ring. This review examines the conventional and green synthesis of metallic and non-metallic BnZ and their derivatives, which have several potential SARs, along with a wide range of pharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, anti-tubercular, and anti-protozoal properties. These compounds have been proven by pharmacological investigations to be efficient against different strains of microbes. Therefore, in this review, the structural variations of BnZ are listed along with various applications, predominantly related to their biological activities.

Effects of Ponderal Index on Neonatal Mortality and Morbidities in Extremely Premature Infants.

BACKGROUND: To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes. METHODS: We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270). RESULTS: The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively; P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants. CONCLUSION: The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.

Effects of Lipopolysaccharide on Oligodendrocyte Differentiation at Different Developmental Stages: an In Vitro Study.

BACKGROUND: Lipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte co-culture model. METHODS: The primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague-Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively. RESULTS: LPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation. CONCLUSION: Repetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.

Validation of noncontact cardiorespiratory monitoring using impulse-radio ultra-wideband radar against nocturnal polysomnography.

PURPOSE: Polysomnography (PSG) is a standard diagnostic test for obstructive sleep apnea (OSA). However, PSG requires many skin-contacted sensors to monitor vital signs of patients, which may also hamper patients' sleep. Because impulse-radio ultra-wideband (IR-UWB) radar can detect the movements of heart and lungs without contact, it may be utilized for vital sign monitoring during sleep. Therefore, we aimed to verify the accuracy and reliability of the breathing rate (BR) and the heart rate (HR) measured by IR-UWB radar. METHOD: Data acquisition with PSG and IR-UWB radar was performed simultaneously in 6 healthy volunteers and in 15 patients with suspected OSA. Subjects were divided into 4 groups (normal, mild OSA, moderate OSA, and severe OSA) according to the apnea-hypopnea index (AHI). BRs and HRs obtained from the radar using a software algorithm were compared with the BRs (chest belt) and the HRs (electrocardiography) obtained from the PSG. RESULTS: In normal and in mild OSA, BRs (intraclass correlation coefficients R [ICCR] 0.959 [0.956-0.961] and 0.957 [0.955-0.960], respectively) and HRs ([ICCR] 0.927 [0.922-0.931] and 0.926 [0.922-0.931], respectively) measured in the radar showed excellent agreement with those measured in PSG. In moderate and severe OSA, BRs ([ICCR] 0.957 [0.956-0.959] and 0.873 [0.864-0.882], respectively) and HRs ([ICCR] 0.907 [0.904-0.910] and 0.799 [0.784-0.812], respectively) from the two methods also agreed well. CONCLUSIONS: The IR-UWB radar could accurately measure BRs and HRs in sleeping patients with OSA. Therefore, IR-UWB radar may be utilized as a cardiopulmonary monitor during sleep.

Mothers' Perceptions of Quality of Family-Centered Care and Environmental Stressors in Neonatal Intensive Care Units: Predictors of and Relationships with Psycho-emotional Outcomes and Postpartum Attachment.

OBJECTIVES: Maternal attachment to promote role development in mothers of preterm infants is critical for babies' optimal growth and development. However, few models specify how neonatal intensive care units (NICUs) and their environments work to foster postpartum attachment (PPA) after preterm birth. We investigated relationships of quality of family-centered care and NICU environmental stressors with maternal PPA, to determine whether these are mediated by mothers' psycho-emotional response and whether pathways to PPA are moderated by developmental immaturity (gestation, birthweight). METHODS: A cross-sectional study using structural equation modeling was conducted on 294 mothers of premature infants with experience in NICUs in over 49 tertiary hospitals in 12 cities or provinces of South Korea. Data were collected using Korean versions of instruments including the Quality of Family-centered Care, Parental Stressor Scale: NICU, and Maternal Postpartum Attachment Scale. RESULTS: Maternal self-representation was a key predictor of PPA (ß = .68), accounting for 42.2% of variance. Multi-group analysis indicated that NICU environmental stressor sensitivity (ß = .26) and maternal self-representation (ß = .67) were predictive of PPA in mothers of moderately preterm and low birthweight (32-36 weeks' gestation, 1500-2499 g birthweight) infants. Quality of family-centered developmental care (ß = .11) and NICU environmental stressor sensitivity (ß = - .16) had significant indirect effects on PPA through psycho-emotional responses. CONCLUSIONS FOR PRACTICE: Healthcare professionals should be aware of the importance of family-centered interventions focusing on psychosocial support and family participation in baby care, based on their environmental role in promoting PPA.

Cognitive Outcomes of Children with Very Low Birth Weight at 3 to 5 Years of Age.

BACKGROUND: The cognitive consequences and risk factors based long-term outcome of very-low-birth-weight (VLBW; < 1,500 g) infants in Korea has not been studied. The aim of this study was to determine the influence of perinatal and neonatal risk factors on the cognitive performance of VLBW children at 3 to 5 years of age. METHODS: We enrolled 88 VLBW infants without cystic periventricular leukomalacia for the assessment of their demographic data, cognitive performance, and development of cerebral palsy (CP) at 3 to 5 years of age. Cognitive performance was assessed using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence IV. Growth data were assessed with measurements of weight, height, and head circumference (HC) at the corrected ages of 6, 12, and 18 months, and 3 to 5 years of age. RESULTS: In the VLBW group, the full-scale intelligence quotient (FSIQ) was 96.1 ± 15.2 at the mean age of 4.5 years. The incidence rate of CP was 3.4%. Overall, 17% (15/88) of the VLBW children had a below-average FSIQ (< 85). We divided the VLBW children into the abnormal FSIQ group (< 85, n = 15) and the normal FSIQ group (≥ 85, n = 73). VLBW children with intrauterine growth retardation (IUGR) was associated with a below-average FSIQ at the mean age of 4.5 years (< 85, 8/15, 53.3% vs. ≥ 85, 5/73, 6.8%; P < 0.001). After controlling for associated clinical factors, IUGR in the VLBW children was found to be associated with an abnormal FSIQ at the mean age of 4.5 years (P = 0.025). The weight, height, and HC obtained for both groups showed that normal growth was maintained at the mean age of 4.5 years with no significant difference between abnormal and normal FSIQ groups. CONCLUSION: Fifteen of 88 (17%) of the VLBW children had a below-average FSIQ (< 85). VLBW with IUGR is associated with poor cognitive outcomes at the mean age of 4.5 years.

Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death.

Arsenic trioxide (ATO; As2O3) has anti-cancer effects in various solid tumors as well as hematological malignancy. Valproic acid (VPA), which is known to be a histone deacetylase inhibitor, has also anti-cancer properties in several cancer cells including lung cancer cells. Combined treatment of ATO and VPA (ATO/VPA) could synergistically enhance anti-cancer effects and reduce ATO toxicity ATO. In this study, the combined anti-cancer effects of ATO and VPA (ATO/VPA) was investigated in NCI-H460 and NCI-H1299 lung cancer cells in vitro and in vivo. A combination of 3 µM ATO and 3 mM VPA (ATO/VPA) strongly inhibited the growths of both lung cancer cell types. DNA flow cytometry indicated that ATO/VPA significantly induced G2/M-phase arrest in both cell lines. In addition, ATO/VPA strongly increased the percentages of sub-G1 cells and annexin V-FITC positive cells in both cells. However, lactate dehydrogenase (LDH) release from cells was not increased in ATO/VPA-treated cells. In addition, ATO/VPA increased apoptosis in both cell types, accompanied by loss of mitochondrial membrane potential (MMP, ∆Ψm), activation of caspases, and cleavage of anti-poly ADP ribose polymerase-1. Moreover, a pan-caspase inhibitor, Z-VAD, significantly reduced apoptotic cell death induced by ATO/VPA. In the xenograft model, ATO/VPA synergistically inhibited growth of NCI-H460-derived xenograft tumors. In conclusion, the combination of ATO/VPA effectively inhibited the growth of lung cancer cells through G2/M-phase arrest and apoptotic cell death, and had a synergistic antitumor effect in vivo.

Quantified Activity Measurement for Medical Use in Movement Disorders through IR-UWB Radar Sensor.

Movement disorders, such as Parkinson's disease, dystonia, tic disorder, and attention-deficit/hyperactivity disorder (ADHD) are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements. As the assessment of most movement disorders depends on subjective rating scales and clinical observations, the objective quantification of activity remains a challenging area. The purpose of our study was to verify whether an impulse radio ultra-wideband (IR-UWB) radar sensor technique is useful for an objective measurement of activity. Thus, we proposed an activity measurement algorithm and quantitative activity indicators for clinical assistance, based on IR-UWB radar sensors. The received signals of the sensor are sufficiently sensitive to measure heart rate, and multiple sensors can be used together to track the positions of people. To measure activity using these two features, we divided movement into two categories. For verification, we divided these into several scenarios, depending on the amount of activity, and compared with an actigraphy sensor to confirm the clinical feasibility of the proposed indicators. The experimental environment is similar to the environment of the comprehensive attention test (CAT), but with the inclusion of the IR-UWB radar. The experiment was carried out, according to a predefined scenario. Experiments demonstrate that the proposed indicators can measure movement quantitatively, and can be used as a quantified index to clinically record and compare patient activity. Therefore, this study suggests the possibility of clinical application of radar sensors for standardized diagnosis.

Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

BACKGROUND/AIMS: Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. METHODS: Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. RESULTS: A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). CONCLUSIONS: Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed.

Rotavirus infection as a frequent cause of neonatal fever.

BACKGROUND: Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. METHOD: We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. RESULTS: All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). CONCLUSIONS: RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns.

Arsenic trioxide induces growth inhibition and death in human pulmonary artery smooth muscle cells accompanied by mitochondrial O2•- increase and GSH depletion.

Arsenic trioxide (ATO; As2 O3 ) induces cell death in various cells via oxidative stress. Expose to chronic arsenic is involved in the development of vascular diseases. However, little is known about the cytotoxic effects of ATO on human normal vascular smooth muscle cells (VSMCs). Thus, in this study, we investigated the effects of ATO on cell growth and death in human pulmonary artery smooth muscle (HPASM) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. ATO treatment decreased the growth of HPASM cells with an IC50 of ∼30-50 µM at 24 h, and ATO induced HPASM cell death via apoptosis or necrosis dependent on the doses of it at this time. Treatment with 50 µM ATO did not increase ROS levels at the early time points, but it significantly increased mitochondrial O2•- levels at 24 h. ATO also induced GSH depletion in HPASM cells. N-acetyl cysteine (NAC; a well-known antioxidant) did not significantly affect apoptotic cell death, ROS levels, or GSH depletion in ATO-treated HPASM cells. However, l-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) intensified mitochondrial O2•- levels in ATO-treated HPASM cells, and significantly increased cell death and GSH depletion in these cells as well. In summary, we provided the first evidence that ATO inhibited the growth of HPASM cells, and induced apoptotic and/or necrotic cell death in these cells, accompanied by increases in mitochondrial O2•- level and GSH depletion.

Simple Age Specific Cutoff Value for Sarcopenia Evaluated by Computed Tomography.

OBJECTIVE: Until now, cutoff values of low skeletal muscle mass using computed tomography (CT) were driven by optimal stratification to predict mortality in cancer patients. The aim of the present study was to investigate the simple, age-specific, cutoff value of low skeletal muscle mass by CT in healthy adults. DESIGN: This is a retrospective, observational, single-center study. SETTING: This study was performed in the health screening department of a university-affiliated hospital during a 10-year period. PATIENTS: Medical records of 1,422 patients presenting to the health screening department were reviewed. Cross-sectional area of psoas muscle at the level of the third lumbar vertebra on abdominal CT was measured and adjusted by height (mm2/m2). This value (psoas muscle index [PMI]) was assumed to represent whole skeletal muscle mass. We divided the patients according to age, sex, and defined cutoff value of low skeletal muscle mass as 2 SDs below the mean. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among 1,422 patients, 550 patients (38.6%) were male. The mean PMI was 896.60 (mm2/m2) for men and 570.54 (mm2/m2) for women. Cutoff values of PMI for men were 592.3 mm2/m2 for 20-39 years, 474.0 mm2/m2 for 40-49 years, 422.2 mm2/m2 for 50-59 years, 374.4 mm2/m2 for 60-69 years, and 331.5 mm2/m2 for 70-89 years. The values for women were 399.9 mm2/m2 for 20-39 years, 287.7 mm2/m2 for 40-49 years, 242.5 mm2/m2 for 50-59 years, 220.4 mm2/m2 for 60-69 years, and 147.6 mm2/m2 for 70-89 years. CONCLUSIONS: Cutoff values of low skeletal muscle mass using CT differed in healthy adults as age increased. Further studies on the effect of sarcopenia intervention using this cutoff value are needed.

Developmental expression of N-methyl-D-aspartate (NMDA) receptor subunits in human white and gray matter: potential mechanism of increased vulnerability in the immature brain.

The pathophysiology of perinatal brain injury is multifactorial and involves hypoxia-ischemia (HI) and inflammation. N-methyl-d-aspartate receptors (NMDAR) are present on neurons and glia in immature rodents, and NMDAR antagonists are protective in HI models. To enhance clinical translation of rodent data, we examined protein expression of 6 NMDAR subunits in postmortem human brains without injury from 20 postconceptional weeks through adulthood and in cases of periventricular leukomalacia (PVL). We hypothesized that the developing brain is intrinsically vulnerable to excitotoxicity via maturation-specific NMDAR levels and subunit composition. In normal white matter, NR1 and NR2B levels were highest in the preterm period compared with adult. In gray matter, NR2A and NR3A expression were highest near term. NR2A was significantly elevated in PVL white matter, with reduced NR1 and NR3A in gray matter compared with uninjured controls. These data suggest increased NMDAR-mediated vulnerability during early brain development due to an overall upregulation of individual receptors subunits, in particular, the presence of highly calcium permeable NR2B-containing and magnesium-insensitive NR3A NMDARs. These data improve understanding of molecular diversity and heterogeneity of NMDAR subunit expression in human brain development and supports an intrinsic prenatal vulnerability to glutamate-mediated injury; validating NMDAR subunit-specific targeted therapies for PVL.

Association of IL23R polymorphism (rs7530511) with intracerebral hemorrhage in Korean population.

Cytokines and their receptors are involved in the development of intracerebral hemorrhage (ICH). Interleukin 23 receptor (IL23R) has been implicated in numerous inflammatory and immune diseases. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of IL23R were associated with the susceptibility of ICH in Korean population. Two coding region SNPs (cSNPs) [rs1884444 (Gln3His), and rs7530511 (Leu310Pro)] were selected, and genotyped in 167 ICH patients and 377 control subjects using direct sequencing. Of two cSNPs, only rs7530511 showed a significant association with ICH in codominant model (C/T vs. C/C, P = 0.017, odds ratio (OR) 4.15, 95 % confidential interval (CI) 1.27-13.58). Allele frequency analysis also revealed that rs7530511 was associated with ICH (P = 0.023, OR 3.68, 95 % CI 1.19-11.32). The frequency of the T allele was increased in the ICH patients, compared to the control subjects. These results suggest that IL23R may contribute to the development of ICH.

Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia.

BACKGROUND: Periventricular leukomalacia (PVL) is a major form of preterm brain injury. Na(+)-K(+)-Cl(-) 1 cotransporter (NKCC1) expression on neurons and astrocytes is developmentally regulated and mediates Cl(-) reversal potential. We hypothesized that NKCC1 is highly expressed on oligodendrocytes (OLs) and increases vulnerability to hypoxia-ischemia (HI) mediated white matter injury, and that the NKCC1 inhibitor bumetanide would be protective in a rodent PVL model. METHODS: Immunohistochemistry in Long-Evans rats and PLP-EGFP transgenic mice was used to establish cell-specific expression of NKCC1 in the immature rodent brain. HI was induced on postnatal day 6 (P6) in rats and the protective efficacy of bumetanide (0.3 mg/kg/i.p. q12h × 60 h) established. RESULTS: NKCC1 was expressed on OLs and subplate neurons through the first 2 postnatal weeks, peaking in white matter and the subplate between P3-7. Following HI, NKCC1 is expressed on OLs and neurons. Bumetanide treatment significantly attenuates myelin basic protein loss and neuronal degeneration 7 d post-HI. CONCLUSION: Presence and relative overexpression of NKCC1 in rodent cerebral cortex coincides with a period of developmental vulnerability to HI white matter injury in the immature prenatal brain. The protective efficacy of bumetanide in this model of preterm brain injury suggests that Cl(-) transport is a factor in PVL and that its inhibition may have clinical application in premature human infants.

Successful Treatment with Ultrasound-Guided Aspiration of Intractable Methicillin-Resistant Staphylococcus aureus Brain Abscess in an Extremely Low Birth Weight Infant.

Brain abscesses are an uncommon and devastating complication of bacteremia in extremely low birth weight infants (<1 kg). We report a 25-week preterm neonate who developed a brain abscess 4 weeks following methicillin-resistant Staphyloccocus aureus (MRSA) sepsis. A huge brain abscess was seen with routine brain sonography on day 19 of life. Despite intravenous vancomycin treatment, the brain abscess increased in size and was associated with increased intracranial pressure on day 49 of life. The brain abscess was accompanied by mild meningeal inflammation with negative blood and cerebrospinal fluid cultures. Diagnosis of abscess was confirmed by bedside ultrasound-guided aspiration, and MRSA was isolated from the pus culture. The MRSA brain abscess refractory to vancomycin was successfully treated by surgical ultrasound-guided percutaneous needle aspiration of brain abscess and prolonged courses of antibiotic administration. At the time of this report, the infant was 9 months old (corrected age was 6 months) and had normal neurodevelopment for her corrected age on the Bayley Infant Neurodevelopmental Screener.

Fluorescence in situ hybridization panel for monitoring of minimal residual disease in patients with double minute chromosomes.

A double minute chromosome (dmin) is a small fragment of extrachromosomal DNA bearing amplified genes observed in malignancies. We investigated the incidence and characteristics of dmins in hematologic malignancies, and the quantitative changes during the treatment follow-up. Once a dmin was observed in conventional G-banding, it was characterized using fluorescence in situ hybridization (FISH) with the panel of MYC, NMYC, and MLL probes. Quantitative changes of malignant cells were measured using G-banding and FISH during the follow up. Dmins were observed in 1.23% of patients (6/489) at the initial diagnosis including 4 with MYC amplification, 1 with MLL and 1 with NMYC. All 6 had complex karyotypes and showed short overall survival (7.7 months). In follow-up specimens, FISH detected dmins in 11 cases out of which G-banding detected dmins in 9 cases. The number of dmins detected by FISH and G-banding did not correlate well. Amplification of NMYC in dmins is reported for the first time. A FISH panel composed of frequently amplified oncogenes (MYC, NMYC, and MLL) in dmins is useful for characterization of dmins. FISH is a sensitive method in detecting dmins and will be useful in monitoring of the minimal residual disease.