Particulate matters (PM2.5, PM10) and the risk of depression among middle-aged and older population: analysis of the Korean Longitudinal Study of Aging (KLoSA), 2016-2020 in South Korea.

BACKGROUND: There is a growing concern that particulate matter (PM) such as PM2.5 and PM10 has contributed to exacerbating psychological disorders, particularly depression. However, little is known about the roles of these air pollutants on depression in elderly. Therefore, this study aimed to examine the association between PM2.5 and PM10, and depression in the elderly population in South Korea. METHODS: We used panel survey data, the Korean Longitudinal Study of Aging (KLoSA), administered by the Labor Institute during the study period of 2016, 2018, and 2020 covering 217 districts in South Korea (n = 7674). Annual district-specific PM2.5 and PM10 concentrations were calculated for the study period from the monthly prediction concentrations produced by a machine-learning-based ensemble model (cross-validated R2: 0.87), then linked to the people matching with year and their residential district. We constructed a generalized estimating equation (GEE) model with a logit link to identify the associations between each of the long-term PM2.5 and PM10 exposures and depression (CES-D 10) after adjusting for individual and regional factors as confounders. RESULTS: In single-pollutant models, we found that long-term 10 [Formula: see text] increments in PM2.5 (OR 1.36, 95% CI 1.20-1.56) and PM10 (OR 1.19, 95% CI 1.10-1.29) were associated with an increased risk of depression in the elderly. Associations were consistent after adjusting for other air pollutants (NO2 and O3) in two-pollutant models. In addition, the impacts substantially differed by regions grouped by the tertile of the population density, for which the risks of particulate matters on depression were substantial in the middle- or high-population-density areas in contrast to the low-population-density areas. CONCLUSIONS: Long-term exposure to PM2.5 and PM10 was associated with a higher risk of developing depression in elderly people. The impact was modified by the population density level of the region where they reside.

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.

Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years' real-world experience in a single institute.

Although the current standard of care for diffuse large B-cell lymphoma (DLBCL) is six cycles of rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone combination chemotherapy (R-CHOP), a larger than expected number of patients cannot complete planned six cycles for various reasons in the real world. We aimed to evaluate the prognosis of patients with DLBCL after incomplete treatment by analyzing the chemotherapy response and survival according to the cause of discontinuation and the number of cycles. We analyzed a retrospective cohort of patients diagnosed with DLBCL who underwent incomplete cycles of R-CHOP at Seoul National University Hospital and Boramae Medical Center from January 2010 to April 2019. A total of 1183 patients were diagnosed with DLBCL, of which 260 (22%) did not complete six cycles of R-CHOP. The most common cause of discontinuation of chemotherapy was life-threatening infection, and the most common pathogen was Pneumocystis jirovecii. Overall survival (OS) and progression-free survival (PFS) were significantly better in patients who achieved complete response (CR) or partial response (PR) at the first response evaluation. Patients underwent three or more cycles of chemotherapy had a longer OS than those who did not. In patients with limited-stage disease, consolidative radiotherapy showed a significant improvement in OS and PFS. Advanced stage, high comorbidity score, and poor primary response to chemotherapy were poor prognostic factors in patients with unplanned treatment shortening. This study provides real-world outcomes for patients who could not complete the planned six cycles of R-CHOP.

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.

Characteristics of Sweet syndrome in patients with or without malignancy.

Sweet syndrome is a neutrophilic dermatosis occasionally associated with malignancies. Due to its rarity, the clinical features of Sweet syndrome are still unclear. Thus, we aimed to analyze clinical features, treatment, and outcomes of these patients according to associated disease. We conducted a retrospective, longitudinal cohort study from January 2000 to August 2020. We reviewed the medical records of 52 patients with Sweet syndrome. The median age of patients was 57.5 years old (range, 17-84), and 48.1% were female. Of the 52 patients analyzed, 27 patients (51.9%) had malignancy-associated Sweet syndrome. Sweet syndrome was diagnosed concurrently with (N = 8), before (N = 5), and after (N = 14) the diagnosis of malignancy. The idiopathic Sweet syndrome was most common in the non-malignancy group (56.0%). Myelodysplastic syndrome was the most common malignancy associated with Sweet syndrome (47.6%). Leukopenia (p = 0.005), anemia (p < 0.001), and thrombocytopenia (p = 0.008) were significantly associated with malignancy. The majority of patients showed rapid improvement of symptoms after steroid administration. The symptoms of some patients with malignancy did not improve with steroid alone; however, their symptoms often improved when steroids were combined with a treatment for the associated malignancy. Relapse and aggravation of Sweet syndrome were common in the malignancy group. Sweet syndrome showed a broad spectrum of clinical features related to various diseases. Sweet syndrome often occurred as a paraneoplastic feature. Therefore, active systemic evaluation is needed in the first diagnosis of Sweet syndrome without clear etiology.

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.

Collective Syntheses of Guaiane Sesquiterpenes: Stereoselective Syntheses of (+)-Dysodensiol F, (+)-10ß,14-Dihydroxy-allo-aromadendrane, and (-)-Dendroside C Aglycon.

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10ß,14-dihydroxy-allo-aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis-fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10ß,14-dihydroxy-allo-aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.

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.

Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy.

BACKGROUND: Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML). METHODS: Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity ( Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy. RESULTS: The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1-68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety. CONCLUSIONS: Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML. TRIAL REGISTRATION: Clinicaltrials.gov NCT02440178, registered May 12th 2015.

Foodborne Viruses Detected Sporadically in the Fresh Produce and Its Production Environment in South Korea.

Contamination of fresh vegetables and berries with human enteric viruses is a major cause of food poisoning. The aim of this study was to investigate the prevalence of norovirus GI, norovirus GII, hepatitis A virus (HAV), adenovirus, astrovirus, rotavirus, and male-specific coliphage systematically in fresh fruit and vegetables and associated agricultural environmental samples, including irrigation water, soil, and worker's gloves. Enteric viruses were detected by international standard methods (ISO/TS 15216), and male-specific coliphages were isolated using US EPA Method 1601. For the study, 773 samples were collected from June 2016 to April 2017, including Chinese cabbage (n = 244), cucumber (n = 98), lettuce (n = 73), strawberry (n = 120), soil (n = 191), irrigation water (n = 14), and gloves (n = 27). Two cucumber and two irrigation water samples were positive for norovirus GI, and one cucumber and two irrigation water samples were positive for norovirus GII. HAV was detected in one strawberry sample and one glove sample. The other tested foodborne viruses were not detected in any of the samples. Sixteen male-specific coliphages were isolated from Chinese cabbage, cucumber, lettuce, cherry tomato, soil, and irrigation water. The isolation of male-specific coliphage would be more practical to investigate the fecal contamination in produce rather than pathogenic viruses.

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.

Dissociative adsorption of a multifunctional compound on a semiconductor surface: a theoretical study of the adsorption of hydroxylamine on Ge(100).

The adsorption behavior of hydroxylamine on a Ge(100) surface was investigated using density functional theory (DFT) calculations. These calculations predicted that hydroxylamine, a multifunctional compound consisting of a hydroxyl group and an amine group, would initially become adsorbed through N-dative bonding, or alternatively through the hydroxyl group via O-H dissociative adsorption. An N-O dissociative reaction may also occur, mainly via N-dative molecular adsorption, and the N-O dissociative product was calculated to be the most stable of all the possible adsorption structures. The calculations furthermore indicated the formation of the N-O dissociative product from the N-dative structure to be nearly barrierless and the dissociated hydroxyl and amine groups to be bonded to two Ge atoms of adjacent Ge dimers. Simulated STM images suggested the change in electron density that would occur upon adsorption of hydroxylamine in various adsorption configurations, and specifically indicated the N-O dissociative product to have greater electron density around the amine groups, and the hydroxyl groups to mainly contribute electron density to the unoccupied electronic states.

Comparison of cladribine- and fludarabine-based induction chemotherapy in relapsed or refractory acute myeloid leukaemia.

Induction regimens integrating cladribine or fludarabine have shown promising outcomes in relapsed or refractory (R/R) acute myeloid leukaemia (AML). We compared the outcome of a cladribine- versus a fludarabine-based regimen as induction chemotherapy for R/R-AML. We included patients with R/R-AML who were treated with a cladribine- or fludarabine-based chemotherapy between 2006 and 2015. We analysed 120 patients, 65 treated with cladribine and 55 treated with fludarabine. The CR rates were 62.7 and 61.4 % for the cladribine group and fludarabine group, respectively (p = 0.890). Poor prognostic factors included older age, secondary AML, poor cytogenetic risk group, prior induction failure, and short first CR duration. No significant overall survival (OS) or relapse-free survival (RFS) differences were found between the groups (OS, p = 0.213; RFS, p = 0.143). However, in a certain subset, survival outcomes were better with cladribine than with fludarabine, including de novo AML, CR at first induction therapy, and not-poor cytogenetic risk group inclusion without overt chemotherapy-refractoriness. By contrast, secondary AML patients had improved survival outcomes when treated with the fludarabine regimen. After CR, better outcomes were observed when allogeneic stem cell transplantation (SCT) was given as consolidation. In R/R-AML, cladribine- and fludarabine-based combination induction chemotherapy had differential survival outcomes according to disease characteristics. Allogeneic SCT after CR with a purine analogue-based regimen improved long-term outcome in these patients.

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.