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Objective: To describe the Bayley Scales of Infant Development 3rd Edition (Bayley-III) of infants discharged home receiving tube feeds., Study Design: Retrospective review of infants discharged with nasogastric or gastrostomy tube feeds and completed a Bayley-III assessment at 2-3-years of age through a neonatal follow-up program. Results were reported using descriptive statistics., Results: Of infants discharged with nasogastric feeds, median Bayley-III scores were in the low-average to average range, and full oral feeds were achieved in 75%. Of infants discharged with gastrostomy tube feeds, median Bayley-III scores were in the extremely low range, and full oral feeds were achieved in 36%. Our data set did not demonstrate a distinct patient demographic that correlated to the type of feeding tube at discharge., Conclusion: Neurodevelopmental outcome at 2-3 years does not appear to be negatively impacted by the decision to discharge an infant from the NICU with home NG feedings., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Intravenous lipids are critical to the care of extremely premature and other high-risk infants., Objectives: This study evaluated safety and efficacy of parenteral nutrition (PN) with composite intravenous lipid emulsion (CO-ILE) with fish oil compared with pure soybean oil lipid emulsion (SOLE)., Methods: Randomized, controlled, double-blind, multicenter study (NCT02579265) in neonates/infants anticipated to require ≥28 d of PN due to gastrointestinal malformations or injury. Duration of the initial and extended treatment phase was 28 d and 84 d, respectively (for patients with PN indication after day 28)., Results: Eighty-three patients (mean postnatal age 11.4 d, 54 preterm) received CO-ILE and 78 patients received SOLE (mean postnatal age 8.3 d, 59 preterm). Thirty-three patients per group completed 28 d of treatment. Risk of having conjugated bilirubin values >2 mg/dL confirmed by a second sample 7 d after the first during the initial treatment phase (primary outcome) was 2.4% (2 of 83) with CO-ILE and 3.8% (3 of 78) with SOLE (risk ratio: 0.59; 95% confidence interval [CI]: 0.09, 3.76). Between days 29 and 84, the number of patients with confirmed conjugated bilirubin values >2 mg/dL did not increase in the CO-ILE group (n = 2) and increased in the SOLE group (n = 9). At the end of the initial treatment phase, conjugated bilirubin concentrations were 45.6% lower under CO-ILE than under SOLE (P = 0.006). There was no clinical or laboratory evidence of essential fatty acid deficiency in patients in the CO-ILE group. Median time to discharge alive was 56.7 d and 66.4 d with CO-ILE and SOLE, respectively (hazard ratio: 1.16; 95% CI: 0.81, 1.68)., Conclusions: CO-ILE was associated with a possible lower risk of cholestasis and significantly lower conjugated bilirubin concentration at the end of the initial treatment phase in high-risk neonates and infants as compared with patients treated with SOLE. In summary, these data indicate that CO-ILE can be considered safe and may be preferable over SOLE in high-risk neonates. This trial was registered at clinicaltrials.gov as NCT02579265., Competing Interests: Conflict of interest Steven Abrams’ institution received support from Fresenius Kabi for his time and effort as principal investigator of this study. Daniel Robinson is an institutional principal investigator, with no salary funding, for a consortium database sponsored by Mead Johnson Nutrition; previously received compensation as a member of the Data Safety Monitoring Board for a clinical investigation sponsored by Fresenius Kabi; and is a consultant for Baxter. Joern-Hendrik Weitkamp serves as consultant for Roche Diagnostics Operations, Inc. All other authors report no conflicts of interest. The institutions of the authors each received institutional research support from Fresenius Kabi for clinical conduct of the trial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors., Methods: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes., Results: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion., Conclusions: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH)., Design: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022., Setting: 41 referral neonatal intensive care units (NICUs) in North America., Patients: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage., Interventions: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS)., Main Outcome Measures: Mortality and meningitis., Results: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort., Conclusions: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%., Competing Interests: Competing interests: ES has received consultant fees from Hospicom on topics unrelated to the subject of this manuscript. UM serves as an advisor for Hope for HIE in an unpaid role, unrelated to the subject of this manuscript. EO is an executive board member of International Society of Pediatric Neurosurgery, which is an unpaid role distinct from this manuscript. MAP has received consultant fees from Chiesi on topics unrelated to the subject of this manuscript. JF consults as an expert reviewer for White & Williams, Cipriani & Werner and Janssen Global Services on topics unrelated to the subject of this manuscript., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Partial replacement of resident Aedes aegypti mosquitoes with introduced mosquitoes carrying certain strains of inherited Wolbachia symbionts can result in transmission blocking of dengue and other viruses of public health importance. Wolbachia strain w AlbB is an effective transmission blocker and stable at high temperatures, making it particularly suitable for hot tropical climates. Following trial field releases in Malaysia, releases using w AlbB Ae. aegypti have become operationalized by the Malaysian health authorities. We report here on an average reduction in dengue fever of 62.4% (confidence intervals 50-71%) in 20 releases sites when compared to 76 control sites in high-rise residential areas. Importantly the level of dengue reduction increased with Wolbachia frequency, with 75.8% reduction (61-87%) estimated at 100% Wolbachia frequency. These findings indicate large impacts of w AlbB Wolbachia invasions on dengue fever incidence in an operational setting, with incidence expected to further decrease as wider areas are invaded., Competing Interests: The authors declare that they do not have conflicting interests., (© 2024 The Author(s).)

Objective: Determine the detection rate from an expanded targeted early cytomegalovirus (CMV) testing program implemented from a large healthcare system (Intermountain Healthcare, IHC)., Study Design: Retrospective review., Setting: Tertiary medical center., Methods: An electronic system was modified to include indications for testing whenever a provider placed an order for CMV testing. A retrospective analysis of this database was performed., Results: From March 1, 2021 to August 31, 2022, there were 3450 (8.8%) patients who underwent CMV testing out of 39,245 total live births within the IHC system. Since the formal implementation of this program in 2019, annual CMV testing has increased almost 10-fold: 2668 CMV tests were performed in 2021 compared to 289 CMV tests in 2015. The most frequent indication for congenital CMV (cCMV) testing was small for gestational age (SGA) (68.2%), followed by macrocephaly (13.5%), an abnormal hearing test (5.0%), and microcephaly (4.4%). Fourteen cCMV-infected infants were diagnosed all of them meeting the criteria for symptomatic cCMV. The most common indication resulting in a positive diagnosis was those who presented with SGA (n = 10 patients). The positivity rate would result in a prevalence of 35.7 symptomatic cCMV cases diagnosed per 100,000 live births, numbers comparable to those expected for universal cCMV screening., Conclusion: An expanded targeted early cCMV testing program may improve detection rates of symptomatic cCMV cases and should be considered as a feasible alternative approach to universal or hearing-targeted early CMV testing., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Introduction: Primary care physicians face the increasing burden of managing multimorbidities in an ageing population. Implementing an integrated care team (ICT) with defined roles and accountability to share consultation tasks is an emerging care model to address this issue. This study compared outcomes with ICT versus usual care for patients with multimorbidities in primary care., Methods: Data was retrospectively extracted from the electronic medical records (EMRs) of consecutive adult Asian patients empanelled to ICT and those in UC at a typical primary care clinic (polyclinic) in eastern Singapore in 2018. The study population had hypertension, and/or hyperlipidaemia and/or type 2 diabetes mellitus (T2DM). Clinical outcomes included the proportion of patients (ICT vs. UC) who attained their treatment goals after 12 months. Process outcomes included the proportion of patients who completed annual diabetic eye and foot screenings, where applicable., Results: Data from 3,302 EMRs (ICT = 1,723, UC = 1,579) from January 2016 to September 2017 was analysed. The ICT cohort was more likely to achieve treatment goals for systolic blood pressure (SBP) (adjusted odds ratio [AOR] = 1.52, 95% confidence interval [CI] = 1.38-1.68), low-density lipoprotein cholesterol (AOR = 1.72, 95% CI = 1.49-1.99), and glycated haemoglobin (AOR = 1.28, 95% CI = 1.09-1.51). The ICT group had higher uptake of diabetic retinal screening (89.1% vs. 83.0%, P < 0.001) and foot screening (85.2% vs. 77.9%, P < 0.001)., Conclusion: The ICT model yielded better clinical and process outcomes than UC, with more patients attaining treatment goals., Competing Interests: None

Background: In 2011, we reported 38 neonates with subgaleal hemorrhage (SH), relating an increasing incidence. It is unclear whether the incidence in our hospitals continued to rise and which risk factors and outcomes are associated with this condition., Design: We retrospectively analyzed every recognized case of SH in our hospitals from the end of our previous report (2010) to the present (2022). We redescribed the incidence, scored severity, tabulated blood products transfused, and recorded outcomes., Results: Across 141 months, 191 neonates were diagnosed with SH; 30 after vacuum or forceps. The incidence (one/1815 births) was higher than in our 2011 report (one/7124 births). Also, severe SH (requiring transfusion) was more common (one/10,033 births vs. one/20,950 births previously). Four died (all with severe SH) and 12 had neurodevelopmental impairment., Conclusion: Recognized cases of SH are increasing in our system without a clear explanation. Adverse outcomes are rare but continue to occur., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Secretion of melatonin, a natural hormone whose receptors are present in the ciliary epithelium, displays diurnal variation in the aqueous humor (AH), potentially contributing to the regulation of intraocular pressure. This study aimed to determine the effects of melatonin on AH secretion in porcine ciliary epithelium. The addition of 100 µM melatonin to both sides of the epithelium significantly increased the short-circuit current (Isc) by ~40%. Stromal administration alone had no effect on the Isc, but aqueous application triggered a 40% increase in Isc, similar to that of bilateral application without additive effect. Pre-treatment with niflumic acid abolished melatonin-induced Isc stimulation. More importantly, melatonin stimulated the fluid secretion across the intact ciliary epithelium by ~80% and elicited a sustained increase (~50-60%) in gap junctional permeability between pigmented ciliary epithelial (PE) cells and non-pigmented ciliary epithelial (NPE) cells. The expression of MT 3 receptor was found to be >10-fold higher than that of MT 1 and MT 2 in porcine ciliary epithelium. Aqueous pre-treatment with MT 1 /MT 2 antagonist luzindole failed to inhibit the melatonin-induced Isc response, while MT 3 antagonist prazosin pre-treatment abolished the Isc stimulation. We conclude that melatonin facilitates Cl - and fluid movement from PE to NPE cells, thereby stimulating AH secretion via NPE-cell MT 3 receptors.

Despite increasing evidence about the value and importance of breastfeeding, less than half of the world's infants and young children (aged 0-36 months) are breastfed as recommended. This Series paper examines the social, political, and economic reasons for this problem. First, this paper highlights the power of the commercial milk formula (CMF) industry to commodify the feeding of infants and young children; influence policy at both national and international levels in ways that grow and sustain CMF markets; and externalise the social, environmental, and economic costs of CMF. Second, this paper examines how breastfeeding is undermined by economic policies and systems that ignore the value of care work by women, including breastfeeding, and by the inadequacy of maternity rights protection across the world, especially for poorer women. Third, this paper presents three reasons why health systems often do not provide adequate breastfeeding protection, promotion, and support. These reasons are the gendered and biomedical power systems that deny women-centred and culturally appropriate care; the economic and ideological factors that accept, and even encourage, commercial influence and conflicts of interest; and the fiscal and economic policies that leave governments with insufficient funds to adequately protect, promote, and support breastfeeding. We outline six sets of wide-ranging social, political, and economic reforms required to overcome these deeply embedded commercial and structural barriers to breastfeeding., Competing Interests: Declaration of interests PB and DM report funding from the WHO Department of Maternal, Newborn, Child and Adolescent Health and Ageing for conducting reviews and specific analyses in preparation of this paper. All other authors declare no competing interests. The findings reported in this manuscript reflect the viewpoints and findings of the authors only, and do not necessarily represent those of the study funder., (© 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

In this paper, we investigate the effect of stimulus payments during the COVID-19 pandemic on the social distancing practices of their recipients. While the directed cash payments stipulated by the 2020 CARES Act were intended to mitigate the economic impact of closures imposed in response to the outbreak, we find that this relief may also have inadvertently contributed to the spread of the virus due to increased social activity. We find that, as the payments were sent out on a staggered weekly schedule, there was a corresponding spike in weekend traffic as indicated by a number of mobility metrics that measure social distancing, over and above the usual uptick expected from weekend shopping following receipt of the stimulus payments on Fridays. This preliminary study gives some indication that the economic benefits of the stimulus package may in fact be outweighed by the detrimental effects of looser social distancing practices prolonging the outbreak., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Hsiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We study the distribution of equity returns in the G20 equity markets to test for contagion following the first official report of a COVID-19 case in China in December 2019 and the subsequent announcement of a global pandemic in March 2020. We find evidence of contagion through equity market tail risk in early 2020 followed by widespread evidence of contagion across multiple channels from the U.S. to G20 equity markets after the pandemic announcement. Our results suggest that global equity markets may be exposed to unpriced pandemic risk factors with implications for portfolio diversification, risk management and financial stability., (© 2021 Elsevier Inc. All rights reserved.)

Premature infants or infants born with complex medical problems are at increased risk of having delayed or dysfunctional oral feeding ability. These patients typically require assisted enteral nutrition in the form of a nasogastric tube (NGT) during their NICU hospitalization. Historically, once these infants overcame their initial reason(s) for admission, they were discharged from the NICU only after achieving full oral feedings or placement of a gastrostomy tube. Recent programs show that these infants can be successfully discharged from the hospital with partial NGT or gastrostomy tube feedings with the assistance of targeted predischarge education and outpatient support. Caregiver opinions have also been reported as satisfactory or higher with this approach. In this review, we discuss the current literature and outcomes in infants who are discharged with an NGT and provide evidence for safe practices, both during the NICU hospitalization, as well as in the outpatient setting., (Copyright © 2022 by the American Academy of Pediatrics.)

We empirically investigate why financial crises spread from one country to another. For our analysis, we develop a new multiple-channel test of financial market contagion and construct indices of crisis severity in equity markets in order to examine how the transmission of shocks across countries can be related to direct linkages between countries or to common characteristics. Based on network analysis with our proposed multiple-channel test for crises between 2007 and 2021, we find that the Great Recession is the most pervasive across countries, followed by the European sovereign debt crisis and the recent COVID pandemic, with the subprime mortgage crisis being the least pervasive. Our main finding is that similar public, private and external debt characteristics are particularly helpful in explaining the transmission of financial shocks during crises. Fiscal deficits appear more important than current account deficits, while stage of economic development matters more than regional linkages, but none of these indicators is as important as debt., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer's disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacologically by increasing acetylcholine. Acetylcholinesterase (AChE) inhibitors have been used to improve cholinergic transmission in the brain for two decades and have proven effective for alleviating symptoms in the early stages of Alzheimer's disease. Therefore, the search for AChE inhibitors for drug development is ongoing. The enzymatic pocket of AChE has long been the target of several drug designs over the last two decades. The peripheral and catalytic sites of AChE are simultaneously bound by several dimeric molecules, enabling more-efficient inhibition. Here, we used 6-chlorotacrine and the tetrahydroquinolone moiety of huperzine A to design and synthesize a series of heterodimers that inhibit AChE at nanomolar potency. Specifically, compound 7b inhibits AChE with an IC 50  < 1 nM and spares butyrylcholinesterase. Administration of 7b to mouse brain slices restores synaptic activity impaired by pirenzepine, a muscarinic M1-selective antagonist. Moreover, oral administration of 7b to C57BL/6 mice enhances hippocampal long-term potentiation in a dose-dependent manner and is detectable in the brain tissue. All these data supported that 7b is a potential cognitive enhancer and is worth for further exploration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: To examine characteristics and outcomes of T18 and T13 infants receiving intensive surgical and medical treatment compared to those receiving non-intensive treatment in NICUs., Study Design: Retrospective cohort of infants in the Children's Hospitals National Consortium (CHNC) from 2010 to 2016 categorized into three groups by treatment received: surgical, intensive medical, or non-intensive., Results: Among 467 infants admitted, 62% received intensive medical treatment; 27% received surgical treatment. The most common surgery was a gastrostomy tube. Survival in infants who received surgeries was 51%; intensive medical treatment was 30%, and non-intensive treatment was 72%. Infants receiving surgeries spent more time in the NICU and were more likely to receive oxygen and feeding support at discharge., Conclusions: Infants with T13 or T18 at CHNC NICUs represent a select group for whom parents may have desired more intensive treatment. Survival to NICU discharge was possible, and surviving infants had a longer hospital stay and needed more discharge supports., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Machine learning (ML) algorithms have been applied to predicting coronary artery disease (CAD). Our purpose was to utilize autoantibody isotypes against four different unmodified and malondialdehyde (MDA)-modified peptides among Taiwanese with CAD and healthy controls (HCs) for CAD prediction. In this study, levels of MDA, MDA-modified protein (MDA-protein) adducts, and autoantibody isotypes against unmodified peptides and MDA-modified peptides were measured with enzyme-linked immunosorbent assay (ELISA). To improve the performance of ML, we used decision tree (DT), random forest (RF), and support vector machine (SVM) coupled with five-fold cross validation and parameters optimization. Levels of plasma MDA and MDA-protein adducts were higher in CAD patients than in HCs. IgM anti-IGKC 76-99 MDA and IgM anti-A1AT 284-298 MDA decreased the most in patients with CAD compared to HCs. In the experimental results of CAD prediction, the decision tree classifier achieved an area under the curve (AUC) of 0.81; the random forest classifier achieved an AUC of 0.94; the support vector machine achieved an AUC of 0.65 for differentiating between CAD patients with stenosis rates of 70% and HCs. In this study, we demonstrated that autoantibody isotypes imported into machine learning algorithms can lead to accurate models for clinical use.

Background: Previous studies have reported that high-dose supplementation of n-3 polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but there is limited evidence of an effect on body fat. We examined the associations of erythrocyte n-3 PUFAs with body fat and fat distribution in a general population consuming a normal diet., Methods: This community-based cross-sectional study included 3075 Chinese (68% women, 40-75 years) recruited between 2008 and 2013. We collected general information and measured anthropometric indices; erythrocyte n-3 PUFAs (including α-C18:3, C20:5, C22:5 and C22:6) by gas-chromatography, and fat mass (FM) and %FM at the total body (TB), android (A) and gynoid (G) regions by dual-energy X-ray absorptiometry (DXA)., Results: Both minimally and maximally adjusted models showed dose-dependent inverse associations of total and individual levels of erythrocyte n-3 PUFAs (except C20:5 n-3[EPA]) with adiposity indices. In the full model, the mean differences between quartiles 4 and 1 of total n-3 PUFAs were -1.60% (BMI), -4.06% (TB FM), -5.38% (A FM), -2.05% (G FM), -2.05% (TB %FM), -3.39% (A %FM) and -2.50% (% A/G); the ORs (95% CI) of %FM-derived obesity (≥25% for men, ≥35% for women) for the highest (vs. lowest) quartile were 0.70 (0.57, 0.86) for total n-3 PUFAs and 0.71 (0.58, 0.87), 0.96(0.78, 1.18), 0.82(0.67, 1.00), 0.66 (0.54, 0.81) for α-C18:3/C20:5/C22:5/C22:6 n-3, respectively. The favourable associations were more pronounced for the DXA-derived FM indices, measurements at the android region and for C22:6 n-3. No significant associations between C20:5 n-3 and the adiposity indices were observed., Conclusions: Higher levels of circulating n-3 PUFAs were dose-dependently associated with better profiles of body fat and fat distribution, particularly in the abdominal regions in this population.

Background: The present study evaluated the effectiveness of a multidisciplinary earlier discharge model for neonates receiving home enteral nutrition (HEN)., Methods: A retrospective data review and analysis was performed on 183 patients discharged out of the neonatal intensive care unit (NICU) receiving partial oral feeds (PO) and partial HEN from September 2016 to March 2018. These patients were followed in a multidisciplinary clinic led by a pediatric gastroenterologist, a neonatal feeding therapist, and a pediatric dietitian. Demographics and data were recorded for patients at discharge, and then chart reviews were performed for additional data., Results: Of 182 patients, 121 (67%) weaned off HEN with a median time to full PO at 79 days (interquartile range [IQR] 15, 247) and had median PO intake of 20% (0, 43) at time of discharge. When comparing patients who gained 100% PO vs patients who did not wean off HEN, the weaned group consisted of 88% nasogastric tubes, with median time off feeds at 27 days (IQR 8, 79) and median PO intake of 29% (11, 50) at discharge. Only 13% of the cohort had an emergency room or hospital admission, which corresponds to 1.6 and 0.8 events, respectively, per 500 tube days specifically due to HEN complications., Conclusions: Our study supports that NICU patients with feeding dysfunction can effectively and safely discharge home earlier while receiving HEN. Our data suggest that a dedicated outpatient clinic can facilitate effective tube weaning in a majority of neonates with complex medical diseases with low rates of adverse events., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Background: Feeding dysfunction is a common consequence of prematurity and illness in neonates, often requiring supplemental nasogastric (NG) or gastrostomy (GT) feeding tubes. A standardized approach to the discharge of infants receiving home enteral nutrition (HEN) is currently lacking., Methods: The Home Enteral Feeding Transitions (HEFT) program was developed to identify patients eligible for HEN and create a standard discharge process. A structured tool helped determine discharge timing and route, and a dedicated outpatient clinic was created for infants discharged on HEN. Demographic, inpatient, and outpatient data were prospectively collected and compared with a historical cohort., Results: A total of 232 infants discharged from our neonatal intensive care unit (NICU) over 9 months met inclusion criteria. Ninety-eight (42%) were discharged with HEN, 68 NG and 30 GT, compared with 134 (58%) receiving full oral feeds. This represented a 10% increase in HEN utilization (P = 0.003) compared with our historical control group. Median HEN length of stay was 31.5 days compared with our historical average of 41 days (P = 0.23). Frequency of emergency department visits and admissions because of HEN was unchanged postintervention. Parents were satisfied (8.6/10), and 98% said they would choose HEN again. The median time to NG discontinuation after discharge was 13.5 days, with an estimated cost savings of $2163 per NICU day., Conclusion: Our program is the first of which we know to use a standard care-process model to guide the decision-making and utilization of HEN at NICU discharge. HEFT shows that HEN at NICU discharge can be safe and effective, with high parental satisfaction., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic small-vessel vasculitic disease that can present with positive MPO-P-ANCA (myeloperoxidase-perinuclear-anti-neutrophil cytoplasmic antibody). It is a rare condition that is difficult to diagnose. We present the case of a 64-year-old man with late-onset adult asthma and treated nasopharyngeal carcinoma who initially presented to us with proximal myopathy. Thereafter, he developed a constellation of fleeting symptoms which included rhinosinusitis, mononeuritis multiplex, skin vasculitis and arthritis. Blood investigations showed that he had eosinophilia, and skin biopsy demonstrated dermal vasculitis with eosinophils. He was found to be MPO-C-ANCA positive, and although initially thought to have granulomatosis with polyangiitis, the diagnosis was later revised to EGPA. This case highlights the diagnostic challenges with atypical presentations of EGPA and also presents a rare case of positive MPO-C-ANCA that has never been described in EGPA before., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Musicians are prone to performance injuries due to the nature of musical practice, and classical pianists are among the groups at high risk for playing-related musculoskeletal disorders (PRMDs). With the growing number of classical pianists in Malaysia, this study aimed to investigate the proportion of PRMDs occurring among classical piano students in tertiary institutions in Malaysia. Associations between gender, practice habits, diet, sports involvement, and PRMD were investigated. A survey was conducted among classical piano students (n=192) at tertiary institutions of Kuala Lumpur and Selangor. Results showed that 35.8% (n=68) students reported having PRMD. The shoulder was the most commonly affected body site, followed by the arm, finger, and wrist. Pain, fatigue, and stiffness were the most cited symptoms by those who suffered from a PRMD. Chi-square analysis showed a significant relationship between the occurrence of PRMD and practice hours (p=0.031), the habit of taking breaks during practice (p=0.045), physical cool-down exercises (p=0.037), and special diet (p=0.007). Multivariate logistic regression analyses confirmed the independent correlation between PRMDs and the lack of taking a break during practice, physical cool-down exercises, and special diet. Because PRMDs are reported at various severity levels, this study should increase awareness of PRMD among classical piano students and encourage injury prevention in musicians in the future to ensure long-lasting music careers.

Professional societies have published recommendations for iron dosing of preterm neonates, but differences exist between guidelines. To help develop standardized guidelines, we performed a 10-year analysis of iron dosing in groups at risk for iron deficiency: IDM (infants of diabetic mothers), SGA (small for gestational age), and VLBW premature neonates (very low birth weight, <1500 g). We analyzed iron dosing after red cell transfusions and erythropoiesis-stimulating agents (ESA). Of IDM, 11.8% received iron in the hospital; 9.8% of SGA and 27.1% of VLBW neonates received iron. Twenty percent of those who received iron had it started by day 14; 63% by 1 month. Supplemental iron was stopped after red cell transfusions in 73% of neonates receiving iron. An ESA was administered to 1677, of which 33% received iron within 3 days. This marked variation indicates that a consistent approach is needed, and using this report and a literature review, we standardized our iron-dosing guidelines., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: In 2001, the US Food and Drug Administration approved recombinant tissue plasminogen activator (alteplase, Cathflo Activase) to reestablish patency of central catheters occluded, presumably, by a fibrin clot. We conducted a multicenter quality improvement study to determine the value of this procedure in our Neonatal Intensive Care Unit (NICUs), including analyses of efficacy, safety and costs., Study Design: We conducted a retrospective quality analysis of neonates in level III NICUs, who received alteplase for the purpose of reestablishing patency of occluded central catheters., Results: Alteplase was administered to 169 neonates, each given one to four doses, totaling 205 episodes of administration. The most common type of catheter where alteplase was used was percutaneously inserted central catheter (PICC) lines (78% of uses), 8% were umbilical venous catheters (UVCs), 6% arterial lines, 5% chest tubes and 3% other catheters. Postnatal age at first dose ranged from 0 to 132 days (median, 12); dosed patients were 22 to 41 weeks gestation at birth (median, 31). Fifty-eight percentage of administrations restored catheter function. Success was more likely at younger postnatal age (10±2 days old in successful vs 14±1 days in unsuccessful treatments; P=0.023). Seventy-two percentage of the re-canalized catheters remained functional until they were no longer needed (2 to 30 days later). Nine percentage of episodes were treated with a second dose 1 to 17 days later for re-occlusion and 50% of those were successful. Bleeding consequences were identified in only one case, where three separate lines were treated (chest tube, PICC and UVC) within a 6-h period. Costs to the health system of doses, minus savings to the system by not needing to replace lines, averaged a net of $34 per dose., Conclusions: The apparent safety and favorable value analysis prompted us to develop a consistent approach to alteplase usage in the Intermountain Healthcare NICUs, using the data in this report to standardize the guidelines across our health system.

Performance injuries among musicians have been widely discussed for decades. However, despite the growing number of classical pianists, this is still a new issue in Malaysia. Therefore, this study aimed to investigate the level of knowledge of playing-related musculoskeletal disorders (PRMDs) among tertiary music students in Malaysia. A survey was conducted among classical piano students at tertiary institutions of Kuala Lumpur and Selangor. Out of 192 respondents, 76% knew that piano playing can cause PRMDs. Slightly over three-quarters of respondents (77.1%) learned about PRMDs from music educators. The survey revealed that the belief in "no pain, no gain" was still ingrained in their minds, as 50.5% respondents believed that pain experienced while playing the piano was normal and 51.6% of them considered that pain must be experienced to improve their piano skill. The respondents were also scored on questions on terminologies of pianist injury and specific PRMD examples: 7.8% of respondents scored high in the questions on the general terminology, while 99.5% of them scored low in the questions on the specific examples of PRMDs. This finding indicated a lack of knowledge of specific musicians' injuries among classical piano students. The attitudes to pain and the level of understanding of the significance of potential injuries indicate that increasing PRMD awareness and introducing courses on PRMD prevention at tertiary institutions are warranted.

Background: Understanding different patterns of fish consumption is an important component for risk assessment of contaminants in fish. A few studies on food consumption had been conducted in Malaysia, but none of them focused specifically on fish consumption. The objectives of this study were to document the meal pattern among three major ethnics in Malaysia with respect to fish/seafood consumption, identify most frequently consumed fish and cooking method, and examine the influence of demographic factors on pattern of fish consumption among study subjects., Methods: A cross-sectional survey was conducted between February 2008 and May 2009 to investigate patterns of fish consumption among Malaysian adults in Peninsular Malaysia. Adults aged 18 years and above were randomly selected and fish consumption data were collected using a 3-day prospective food diary., Results: A total of 2,675 subjects, comprising male (44.2%) and female (55.7%) participants from major ethnics (Malays, 76.9%; Chinese, 14.7%; Indians, 8.3%) with a mean age of 43.4±16.2 years, were involved in this study. The results revealed 10 most frequently consumed marine fish in descending order: Indian mackerel, anchovy, yellowtail and yellow-stripe scads, tuna, sardines, torpedo scad, Indian and short-fin scads, pomfret, red snapper, and king mackerel. Prawn and squid were also among the most preferred seafood by study subjects. The most frequently consumed freshwater fish were freshwater catfish and snakehead. The most preferred cooking style by Malaysians was deep-fried fish, followed by fish cooked in thick and/or thin chili gravy, fish curry, and fish cooked with coconut milk mixed with other spices and flavorings. Overall, Malaysians consumed 168 g/day fish, with Malay ethnics' (175±143 g/day) consumption of fish significantly (p<0.001) higher compared with the other two ethnic groups (Chinese=152±133 g/day, Indians=136±141 g/day)., Conclusion: Fish consumption was significantly associated with ethnicity, age, marital status, residential area, and years of education of adults in Peninsular Malaysia, and the data collected are beneficial for the purpose of health risk assessment on the intake of contaminants through fish/seafood consumption.

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD)., Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive-behavioural therapy-based psychoeducation and usual care., Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK&#95;CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels., Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only., Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms., (© The Royal College of Psychiatrists 2016.)

Spatio-temporal patterns of dengue risk in Malaysia were studied both at the address and the sub-district level in the province of Selangor and the Federal Territory of Kuala Lumpur. We geocoded laboratory-confirmed dengue cases from the years 2008 to 2010 at the address level and further aggregated the cases in proportion to the population at risk at the sub-district level. Kulldorff's spatial scan statistic was applied for the investigation that identified changing spatial patterns of dengue cases at both levels. At the address level, spatio-temporal clusters of dengue cases were concentrated at the central and south-eastern part of the study area in the early part of the years studied. Analyses at the sub-district level revealed a consistent spatial clustering of a high number of cases proportional to the population at risk. Linking both levels assisted in the identification of differences and confirmed the presence of areas at high risk for dengue infection. Our results suggest that the observed dengue cases had both a spatial and a temporal epidemiological component, which needs to be acknowledged and addressed to develop efficient control measures, including spatially explicit vector control. Our findings highlight the importance of detailed geographical analysis of disease cases in heterogeneous environments with a focus on clustered populations at different spatial and temporal scales. We conclude that bringing together information on the spatio-temporal distribution of dengue cases with a deeper insight of linkages between dengue risk, climate factors and land use constitutes an important step towards the development of an effective risk management strategy.

Room-temperature sodium-ion batteries have the potential to become the technology of choice for large-scale electrochemical energy storage because of the high sodium abundance and low costs. However, not many materials meet the performance requirements for practical applications. Here, we report a novel sodium-ion battery electrode material, Na(2.55)V(6)O(16)⋅0.6 H(2)O, that shows significant capacities and stabilities at high current rates up to 800 mA g(-1). X-ray photoelectron spectroscopy measurements are carried out to better understand the underlying reactions. Moreover, due to the different oxidation states of vanadium, this material can also be employed in a symmetric full cell, which would decrease production costs even further. For these full cells, capacity and stability tests are conducted using various cathode:anode mass ratios., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fluorescence excitation enhancement by plasmonic nanostructures such as gold nanohole arrays has been a hot topic in biosensing and bioimaging in recent years. However, the high throughput and high yield fabrication of precisely designed metal nanostructures for optimized fluorescence excitation remains a challenge. Our work is the first report combining nanopattern nickel mould fabrication and UV imprinting for gold nanostructure mass fabrication in high yield. We report our successful gold nanohole array mass fabrication on a 4'' glass wafer, by first fabricating a high fidelity nickel mould, then using the mould for UV nanoimprinting on a polymer coated on the glass, evaporating the gold film on the glass wafer, and lifting off the polymer to obtain a gold nanohole array on the glass. Our optimized process for wafer fabrication can achieve almost 100% yield from nanoimprinting to gold lift-off, while the fabricated nickel mould has >70% defect-free area with the rest having a few scattered defects. In our work, the size and pitch of the gold nanohole array are designed to enhance the fluorescent dye Alexa 647. When the fabricated gold nanohole array is used for prostate specific antigen (PSA) detection by establishing a sandwiched fluorescence assay on the gold surface, a detection limit of 100 pg ml(-1) is achieved, while with a same thickness of gold film, only 1 ng ml(-1) is detected.

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error in the metabolism of the urea cycle with an incidence of 1 in 14,000 live births. Pregnancy can trigger potentially fatal hyperammonemic crises. We report a successful pregnancy in a 29-year-old primiparous patient with a known diagnosis of OTC deficiency since infancy. Hyperammonemic complications were avoided due to careful multidisciplinary management which included a detailed antenatal, intrapartum and postnatal plan. Management principles include avoidance of triggers, a low-protein diet and medications which promote the removal of nitrogen by alternative pathways. Triggers include metabolic stress such as febrile illness, particularly gastroenteritis, fasting and any protein loading. In our case the patient, in addition to a restricted protein intake, was prescribed sodium benzoate 4 g four times a day, sodium phenylbutyrate 2 g four times a day and arginine 500 mg four times a day to aid excretion of ammonia and reduce flux through the urea cycle.

The Faradaic electrochemical impedance technique is employed to characterize the impedance change of a nanoporous alumina biosensor in response towards the specific binding of dengue serotype 2 (Denv2) viral particles to its serotype 2-specific immunoglobulin G antibody within the thin alumina layer. The optimal equivalent circuit model that matches the impedimetric responses of the sensor describes three distinct regions: the electrolyte solution (R(s)), the porous alumina channels (including biomaterials) (Q(1), R(1)) and the conductive electrode substrate layer (Q(2), R(2)). Both channel resistance R(1) and capacitance Q(1) change in response to the increase of the Denv2 virus concentration. A linear relationship between R(1) and Denv2 concentration from 1 to 900 plaque forming unit per mL (pfu mL(-1)) can be derived using Langmuir-Freundlich isotherm model. At 1pfu mL(-1) Denv2 concentration, R(1) can be distinguished from that of the cell culture control sample. Moreover, Q(1) doubles when Denv2 is added but remains unchanged in the presence of two other non-specific viruses - West Nile virus and Chikungunya virus indicates biosensor specificity can be quantitatively measured using channel capacitance., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A 36-year-old, healthy, primiparous female underwent a caesarean section under general anaesthetic. She had previously had a severe reaction to dye during a myelogram and therefore, had declined epidural analgesia or regional anaesthesia. Induction and maintenance of anaesthesia was uneventful, but on emergence, and before tracheal extubation, the patient coughed on the endotracheal tube and almost immediately developed right-sided subcutaneous emphysema of the face and neck. At this point her oxygen saturation began to fall and she was noted to be difficult to ventilate. Clinically and radiologically, she had a right-sided pneumothorax which was treated immediately with intercostal drain insertion. She went on to develop a left pneumothorax which also required intercostal drain insertion. She made an uneventful recovery and was discharged 8 days later. A subsequent CT scan of her chest revealed no pre-existing primary pulmonary pathology that would have accounted for the pneumothoraces.

Background: The present study examined the effectiveness of three staff training elements: psychoeducation (PE) on autism, introduction of functional behavioural analysis (FBA) and emotional management (EM), on the reaction of challenging behaviours for frontline staff towards children with autism in Hong Kong special education settings., Methods: A sample of 311 frontline staff in educational settings was recruited to one of the three conditions: control, PE-FBA and PE-FBA-EM groups. A total of 175 participants completed all three sets of questionnaires during pre-training, immediate post-training and 1-month follow-up., Results: Findings showed that the one-session staff training workshop increased staff knowledge of autism and perceived efficacy but decrease helping behavioural intention., Conclusions: In spite of the limited effectiveness of a one-session staff training workshop, continued staff training is still necessary for the improvement of service quality. Further exploration on how to change emotion response of staff is important., (© 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.)

While infantile myofibromatosis is the most common mesenchymal tumour of infancy, only around 300 cases have been reported. The authors report a 33-year-old para 1 with an uncomplicated, dichorionic diamniotic twin pregnancy who was diagnosed with an intrauterine death of one twin at 36+5 weeks gestation. At caesarean section, a macerated male stillborn weighing 2.72 kg was delivered. Postmortem examination revealed a pedunculated lesion attached to the left shoulder and underlying muscle consistent with a congenital myofibroma. The cause of death was postulated to be haemorrhage from the tumour surface causing fetal anaemia.

Background: Research suggests that an eight-week Mindfulness-Based Cognitive Therapy (MBCT) program may be effective in the treatment of generalized anxiety disorders. Our objective is to compare the clinical effectiveness of the MBCT program with a psycho-education programme and usual care in reducing anxiety symptoms in people suffering from generalized anxiety disorder., Methods: A three armed randomized, controlled clinical trial including 9-month post-treatment follow-up is proposed. Participants screened positive using the Structure Clinical Interview for DSM-IV (SCID) for general anxiety disorder will be recruited from community-based clinics. 228 participants will be randomly allocated to the MBCT program plus usual care, psycho-education program plus usual care or the usual care group. Validated Chinese version of instruments measuring anxiety and worry symptoms, depression, quality of life and health service utilization will be used. Our primary end point is the change of anxiety and worry score (Beck Anxiety Inventory and Penn State Worry Scale) from baseline to the end of intervention. For primary analyses, treatment outcomes will be assessed by ANCOVA, with change in anxiety score as the baseline variable, while the baseline anxiety score and other baseline characteristics that significantly differ between groups will serve as covariates., Conclusions: This is a first randomized controlled trial that compare the effectiveness of MBCT with an active control, findings will advance current knowledge in the management of GAD and the way that group intervention can be delivered and inform future research. Unique Trail Number (assigned by Centre for Clinical Trails, Clinical Trials registry, The Chinese University of Hong Kong): CUHK&#95;CCT00267.

Background: Antipsychotics are associated with a wide range of side-effects. Many patients experience antipsychotics as unpleasant and something they would rather avoid, leading some of them to discontinue taking their medication. The importance of evaluating the patients' perspective, especially their attitudes toward medication in the presence of side-effects, has long been emphasized. However, no definite conclusion has been made to date on the relationship between antipsychotic side-effects and attitudes toward medication., Objectives: The objective of this systematic review was to determine the best available evidence regarding the impact of antipsychotic side-effects on attitudes toward medication in patients with schizophrenia and related disorders, which include schizoaffective and schizophreniform disorders., Inclusion Criteria: Types of studies - This review considered quantitative studies that examined the magnitude of the effect of antipsychotic side-effects on attitudes toward medication in patients with schizophrenia.Types of participants - This review considered studies that included adults aged 18 to 70 years old, with a confirmed diagnosis of schizophrenia or related disorders, and receiving antipsychotic treatment in any healthcare setting.Types of intervention - This review included studies that investigated the impact of antipsychotic side-effects using standardised scales.Types of outcomes - This review included studies that quantitatively measure attitudes toward medication using standardised scales. Attitudes toward medication refer to the patients' perception towards different aspects of medication including, but not limited to, medication-taking, medication effects, and/or medication side-effects., Search Strategy: The search aimed to find published studies using a range of databases. A search strategy was developed using all identified keywords, and it was extended to the following databases: MEDLINE, CINAHL, PsycINFO, Scopus, ScienceDirect, and Web of Science. The search was limited to studies in English language and those published between the years 1990 to 2009., Methodological Quality: Selected studies were assessed by two reviewers for methodological quality using the appropriate JBI critical appraisal instrument., Data Collection: Data was extracted from the included studies using the appropriate JBI data extraction instrument., Data Analysis: The heterogenous nature of the studies prevented statistical pooling of the data, thus the findings were presented in a narrative summary., Results: A total of 13 studies were included in the review. Two studies found a positive relationship between attitudes toward medication and antipsychotic side-effects, while another five studies found a positive relationship between attitudes toward medication and specific side-effects such as sedation, concentration difficulties, increased sleep, diminished sexual desire, and extrapyramidal side-effects, specifically dyskinesia and parkinsonism. The remaining six studies found no positive relationship between attitudes and side-effects., Conclusions: This review provides some support to the notion that patients experiencing antipsychotic side-effects are at risk of developing more negative attitudes toward medication. Implications for practice - Regular attitude assessments should be conducted for patients with side-effects, and prompt clinical interventions and patient education can be carried out to manage side-effects. Implications for research - There is a need for more quantitative studies to further understand the relationship between the two variables.

Context: Previous studies have suggested that preventive health care measures may be improved by proactive patient-reminder systems and use of electronic medical databases., Objective: Our objective was to use Kaiser Permanente's (KP's) electronic medical databases to improve the preventive health care delivered to KP patients in Honolulu, HI., Design: Patients not seen by their primary care physician in more than one year ("low-utilizing patients") and overdue for preventive health care services were identified using KP's electronic medical databases. These patients were then sent letters requesting that they obtain these services. Response rates and results of their screening tests were tracked., Results: Of 309 letters sent, 84 (27.2%) patients responded. Of the 260 patients who were reminded of overdue immunizations (tetanus, pneumonia, influenza, or a combination of these), 51 (19.6%) came in to obtain them. Ten of the 37 (27.0%) women overdue for breast cancer screening came in for mammograms. Eleven of the 109 (10.1%) patients overdue for colorectal cancer screening completed fecal occult blood testing., Conclusion: Outreach letters that target low-utilizing patients identified by an electronic medical database may be an efficient and cost-effective way of improving patient use rates of preventive health care.

Introduction: Over the years, patients presented with cerebrofacial vascular malformations which occurred in clusters. The syndromic presentation suggested angio-architectural abnormality, which started to develop during embryogenesis. The segmentation of the neural tube could provide a rational explanation for such a neuropathological phenomenon. Based on this theory, cerebrofacial arteriovenous metameric syndrome (CAMS) was derived. This describes clinical association between arteriovenous malformations of the face, retina, and brain. In this case's presentation, the syndromic presentation of the patient provided further evidence to the theory., Case Report: The authors report a case of a male neonate presenting with heart failure at birth. He was found to have a left sigmoid dural arteriovenous fistula (dAVF), an upper lip arteriovenous malformation (AVM), and a capillary hemangioma over the nose. The neuropathological clustering of vascular lesions is suggestive of CAMS. The patient was successfully treated with endovascular treatment and showed normal development during our follow-up assessment., Conclusion: With the evolving evidence for the embryo-developmental theory for the clustering of angio-pathological lesions, further study and development of pathophysiology should be continued in following this track of theory. The success of endovascular intervention has warranted a favorable treatment option.

Chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance (PVR) and leads to structural abnormalities of the lung circulation in newborn sheep. Compared with normal lambs born at term, chronically ventilated preterm lambs have increased pulmonary arterial smooth muscle and elastin, fewer lung microvessels, and reduced abundance of endothelial nitric oxide synthase. These abnormalities may contribute to impaired respiratory gas exchange that often exists in infants with chronic lung disease (CLD). Nitric oxide inhalation (iNO) reduces PVR in human infants and lambs with persistent pulmonary hypertension. We wondered whether iNO might have a similar effect in lambs with CLD. We therefore studied the effect of iNO on PVR in lambs that were delivered prematurely at approximately 125 days of gestation (term = 147 days) and mechanically ventilated for 3 wk. All of the lambs had chronically implanted catheters for measurement of pulmonary vascular pressures and blood flow. During week 2 of mechanical ventilation, iNO at 15 parts/million for 1 h decreased PVR by approximately 20% in 12 lambs with evolving CLD. When the same study was repeated in eight lambs at the end of week 3, iNO had no significant effect on PVR. To see whether this loss of iNO effect on PVR might reflect dysfunction of lung vascular smooth muscle, we infused 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP; 150 microg. kg(-1). min(-1) iv) for 15-30 min in four of these lambs at the end of week 3. PVR consistently decreased by 30-35%. Lung immunohistochemistry and immunoblot analysis of excised pulmonary arteries from lambs with CLD, compared with control term lambs, showed decreased soluble guanylate cyclase (sGC). These results suggest that loss of pulmonary vascular responsiveness to iNO in preterm lambs with CLD results from impaired signaling, possibly related to deficient or defective activation of sGC, the intermediary enzyme through which iNO induces increased vascular smooth muscle cell cGMP and resultant vasodilation.

Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO.) was measured in the expired gas of children with asthma. Vital capacity expirates from 21 control subjects and 13 subjects with asthma were assayed by chemiluminescence. Measurements were highly reproducible (coefficient of variation, 2.6% +/- 1.1%) and did not vary with age, sex, height, or weight. Patients with asthma had mean NO. levels (16.3 parts per billion) that were more than threefold higher than those of control subjects (5.05 ppb; p < 0.001). Expired NO. decreased as airflow obstruction improved during corticosteroid treatment (r2 = 0.77; n = 7; p < 0.001) but remained higher than normal (13.5 ppb; n = 5; p < 0.01) even after airflow obstruction resolved. We demonstrate the use of a reproducible test for asthma in children that is independent of measures of airflow obstruction. We speculate that expired NO assays may prove to be a more sensitive measure of childhood asthma than spirometry.

Neurogenesis occurs in adult song birds, which suggests that neurons born after hatching may contribute to histogenesis and plasticity of the avian brain. However, little is known about the overall contribution to the mature brain of neurons born in juveniles and adults, and how this process affects different regions of the avian brain. In fact, studies of the histogenesis of the avian forebrain have made the classical assumption that neuronal birth ends before hatching. Here we determined the contribution of neurons born before and after hatching to different regions throughout the adult canary brain. Male canaries were injected with [3H]-thymidine at different times during embryonic, juvenile, and adult life. The position of labeled neurons was mapped in parasagittal brain sections. Because all birds were killed as adults, results indicate the time of birth of neurons that survived to adulthood in different structures of the avian brain. Injection at embryonic day (E) 5 or E9 resulted in labeled neurons in all regions of the neuroaxis. The vast majority of neurons outside of the telencephalon were born before E9. One exception was a discrete region in the dorsal thalamus, a part of the song-control circuit, where neurons continued to be born after E9. Most regions of the telencephalon had a high proportion of its neurons labeled by the embryonic injections. In particular, archistriatum, anterior neostriatum, and the hippocampus had most of their neurons labeled before hatching. This indicates that many of the telencephalic neurons born in the embryo are long lived and are not replaced by other neurons that continue to be added to the telencephalon after hatching. Neurons labeled by [3H]-thymidine injections after hatching were restricted to the telencephalon and contributed importantly to many regions. In particular, the avian striatum (lobus parolfactorius, LPO) received a large number of its neurons during the first 20 days of life, but continued to incorporate new neurons throughout juvenile and adult life. Neurons continued to be added to the telencephalon of adults (even in 4-year-old birds). The distribution of labeled neurons after [3H]-thymidine injections in adults was similar to that observed in latter stages of juvenile development. The contribution of neurons born at different ages from embryonic development to adulthood varied among different anatomical subdivisions of the canary brain. this could, in part, explain differences in the cytoarchitecture and plasticity between brain regions. Neurogenesis after hatching may allow the modification of selected brain circuits as the bird matures and ages.

It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brain assembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43%-0.64% of the HVC neurons present at 1 year of age are labeled per day of [3H]-thymidine injection. [3H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning.