Prevalence of Invasive Bacterial Infection in Hypothermic Young Infants: A Multisite Study.

OBJECTIVE: To determine the prevalence of bacteremia and meningitis (invasive bacterial infection [IBI]) in hypothermic young infants, and also to determine the prevalence of serious bacterial infections (SBI) and neonatal herpes simplex virus and to identify characteristics associated with IBI. STUDY DESIGN: We conducted a retrospective cohort study of infants ≤90 days of age who presented to 1 of 9 hospitals with historical or documented hypothermia (temperature ≤36.0°C) from September 1, 2017, to May 5, 2021. Infants were identified by billing codes or electronic medical record search of hypothermic temperatures. All charts were manually reviewed. Infants with hypothermia during birth hospitalization, and febrile infants were excluded. IBI was defined as positive blood culture and/or cerebrospinal fluid culture treated as a pathogenic organism, whereas SBI also included urinary tract infection. We used multivariable mixed-effects logistic regression to identify associations between exposure variables and IBI. RESULTS: Overall, 1098 young infants met the inclusion criteria. IBI prevalence was 2.1% (95% CI, 1.3-2.9) (bacteremia 1.8%; bacterial meningitis 0.5%). SBI prevalence was 4.4% (95% CI, 3.2-5.6), and neonatal herpes simplex virus prevalence was 1.3% (95% CI, 0.6-1.9). Significant associations were found between IBI and repeated temperature instability (OR, 4.9; 95% CI, 1.3-18.1), white blood cell count abnormalities (OR, 4.8; 95% CI, 1.8-13.1), and thrombocytopenia (OR, 5.0; 95% CI, 1.4-17.0). CONCLUSIONS: IBI prevalence in hypothermic young infants is 2.1%. Further understanding of characteristics associated with IBI can guide the development decision tools for management of hypothermic young infants.

Plasma Biomarkers of Evolving Encephalopathy and Brain Injury in Neonates with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: The objective of the study was to evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. STUDY DESIGN: Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. RESULTS: Sixty-two patients were included. Elevated Tau levels on days 2-3 of TH were associated with death or severe injury on MRI (aOR: 1.06, 95% CI: 1.03-1.09; aOR: 1.04, 95% CI: 1.01-1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP index) on the same day (P = .022). CONCLUSIONS: Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger-scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

Modeling protected species distributions and habitats to inform siting and management of pioneering ocean industries: A case study for Gulf of Mexico aquaculture.

Marine Spatial Planning (MSP) provides a process that uses spatial data and models to evaluate environmental, social, economic, cultural, and management trade-offs when siting (i.e., strategically locating) ocean industries. Aquaculture is the fastest-growing food sector in the world. The United States (U.S.) has substantial opportunity for offshore aquaculture development given the size of its exclusive economic zone, habitat diversity, and variety of candidate species for cultivation. However, promising aquaculture areas overlap many protected species habitats. Aquaculture siting surveys, construction, operations, and decommissioning can alter protected species habitat and behavior. Additionally, aquaculture-associated vessel activity, underwater noise, and physical interactions between protected species and farms can increase the risk of injury and mortality. In 2020, the U.S. Gulf of Mexico was identified as one of the first regions to be evaluated for offshore aquaculture opportunities as directed by a Presidential Executive Order. We developed a transparent and repeatable method to identify aquaculture opportunity areas (AOAs) with the least conflict with protected species. First, we developed a generalized scoring approach for protected species that captures their vulnerability to adverse effects from anthropogenic activities using conservation status and demographic information. Next, we applied this approach to data layers for eight species listed under the Endangered Species Act, including five species of sea turtles, Rice's whale, smalltooth sawfish, and giant manta ray. Next, we evaluated four methods for mathematically combining scores (i.e., Arithmetic mean, Geometric mean, Product, Lowest Scoring layer) to generate a combined protected species data layer. The Product approach provided the most logical ordering of, and the greatest contrast in, site suitability scores. Finally, we integrated the combined protected species data layer into a multi-criteria decision-making modeling framework for MSP. This process identified AOAs with reduced potential for protected species conflict. These modeling methods are transferable to other regions, to other sensitive or protected species, and for spatial planning for other ocean-uses.

Soluble Carrier Transporters and Mitochondria in the Immunometabolic Regulation of Macrophages.

Significance: Immunometabolic regulation of macrophages is a growing area of research across many fields. Here, we review the contribution of solute carriers (SLCs) in regulating macrophage metabolism. We also highlight key mechanisms that regulate SLC function, their effects on mitochondrial activity, and how these intracellular activities contribute to macrophage fitness in health and disease. Recent Advances: SLCs serve as a major drug absorption pathway and represent a novel category of therapeutic drug targets. SLC dynamics affect cellular nutritional sensors, such as AMP-activated protein kinase and mammalian target of rapamycin, and consequently alter the cellular metabolism and mitochondrial dynamics within macrophages to adapt to a new functional phenotype. Critical Issues: SLC function affects macrophage phenotype, but their mechanisms of action and how their functions contribute to host health remain incompletely defined. Future Directions: Few studies focus on the impact of solute transporters on macrophage function. Identifying which SLCs are present in macrophages and determining their functional roles may reveal novel therapeutic targets with which to treat metabolic and inflammatory diseases. Antioxid. Redox Signal. 36, 906-919.

Characteristics of Patients with Hypertension at a Nicaraguan Clinic.

OBJECTIVE: Describe the characteristics and pharmacological management of hypertensive patients in a Nicaraguan ambulatory care clinic. METHODS: The study analyzed a random sample of 349 charts of patients aged older than 18 years from an ambulatory care clinic in Nicaragua and analyzed those who were diagnosed or had a known history of hypertension. RESULTS: Out of 349 patients, 19.77% (n=69) had a history of hypertension. Hypertensive patients were 66.2% female (n=45) with mean age of 56.1 years (SD=13.7). The most common comorbid condition was type 2 diabetes mellitus, which was present in 18.8% (n=13) of hypertensive patients. Other comorbid conditions included 10% (n=7) with chronic kidney disease and 75.8% (n=50) who were either overweight or obese. The most commonly prescribed antihypertensive medications were losartan, captopril, and enalapril. CONCLUSIONS: Hypertension is common in this clinic population and most commonly treated with angiotension-receptor blockers or angiotensin converting enzyme inhibitors.

Point-of-Care Ultrasound as Part of a Short-Term Medical Mission to Rural Nicaragua.

OBJECTIVES: The lack of access to diagnostic imaging in resource-limited settings (RLSs) poses a worldwide problem. Advances in ultrasound (US) imaging technology bridge this gap, particularly when examinations are performed by physicians and integrated into the patient encounter, termed point-of-care ultrasound (POCUS). Because the number of physicians participating in short-term medical missions (STMMs) is increasing, the authors sought to characterize how the use of POCUS would affect care delivered as part of a 1-week outreach trip in rural Nicaragua. METHODS: In February 2017, as part of an ongoing collaboration among the University of South Carolina, the Medical University of South Carolina, and OneWorld Health, the authors conducted an observational prospective study of all of the patients who received a POCUS examination as part of standard clinical practice during an STMM to Sébaco, Nicaragua. The goal was to determine how often POCUS changed medical management. In addition, the number and types of scans performed were recorded to assess the most common reasons for POCUS use. RESULTS: More than 1100 patients were seen, and a total of 79 POCUS examinations were performed on 59 patients by 2 physicians with extensive POCUS training. Eighty percent of the patients were women, with an average age of 40.5 years (range 1.6-87 years). The use of US changed management for 35.6% of total patients examined (N = 21), divided among changes in diagnosis, pharmacotherapy, new referral, or referral not needed. The average time to perform a POCUS examination was 6.0 minutes. A wide range of POCUS examinations were performed, with lung, gallbladder, obstetric/gynecologic, and cardiac examinations performed most often. CONCLUSIONS: Incorporating POCUS by trained physicians in an RLS as part of an STMM was successful and often changed management. As interest in nonemergency and noncritical care POCUS increases and proliferation of low-cost, accurate, handheld US devices continues, it is probable that more physicians traveling to RLSs will use POCUS as part of STMMs, positively affecting patient care.

Orange juice affects acylcarnitine metabolism in healthy volunteers as revealed by a mass-spectrometry based metabolomics approach.

Citrus juices, especially orange juice, constitute rich sources of bioactive compounds with a wide range of health-promoting activities. Data from epidemiological and in vitro studies suggest that orange juice (OJ) may have a positive impact on lipid metabolism. However, the effect of orange juice intake on blood lipid profile is still poorly understood. We have used two different blood samples, Dried Blood Spots (DBS) and plasma, to assess the effect of two-week orange juice consumption in healthy volunteers by a mass-spectrometry based metabolomics approach. DBS were analysed by liquid chromatography mass spectrometry (LC-MS) and plasma samples were analysed by the gas chromatography mass spectrometry (GC-MS). One hundred sixty-nine lipids including acylcarnitines (AC), lysophosphatidylcholines (LysoPC), (diacyl- and acyl-alkyl-) phosphatidylcholines (PC aa and PC ae) and sphingomyelins (SM) were identified and quantified in DBS. Eighteen fatty acids were identified and quantified in plasma. Multivariate analysis allowed to identify an increase in C3:1, C5-DC(C6-OH), C5-M-DC, C5:1-DC, C8, C12-DC, lysoPC18:3, myristic acid, pentadecanoic acid, palmitoleic and palmitic acid and a decrease in nervonic acid, C0, C2, C10, C10:1, C16:1, C16-OH, C16:1-OH, C18-OH, PC aa C40:4, PC ae C38:4, PC ae C42:3, PC ae C42:4 and cholesterol levels after orange juice intake. A two-week period of orange juice intake could affect fatty acids ß-oxidation through mitochondrial and peroxisomal pathways, leading to an increase of short-chain acylcarnitines and a decrease of medium and long-chain acylcarnitines. This is the first report analyzing the effect of orange juice intake in healthy volunteers using a dried blood spot-based metabolomics approach.

Steric Clash in the SET Domain of Histone Methyltransferase NSD1 as a Cause of Sotos Syndrome and Its Genetic Heterogeneity in a Brazilian Cohort.

Most histone methyltransferases (HMTase) harbor a predicted Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, an HMTase at 5q35.2-35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations. Using protein modeling and bioinformatic approaches, we evaluated the effects of one novel (I2007F) and 21 previously reported missense mutations in the SET domain. For the I2007F mutation, we observed conformational change and loss of structural stability in Molecular Dynamics (MD) simulations which may lead to loss-of-function of the SET domain. For six mutations near the ligand-binding site we observed in simulations steric clashes with neighboring side chains near the substrate S-Adenosyl methionine (SAM) binding site, which may disrupt the enzymatic activity of NSD1. These results point to a structural mechanism underlying the pathology of the NSD1 missense mutations in the SET domain in Sotos syndrome. NSD1 mutations were identified in only 32% of the Brazilian Sotos patients in our study cohort suggesting other genes (including unknown disease genes) underlie the molecular etiology for the majority of these patients. Our studies also found NSD1 expression to be profound in human fetal brain and cerebellum, accounting for prenatal onset and hypoplasia of cerebellar vermis seen in Sotos syndrome.

Efficacy of chest compressions directed by end-tidal CO2 feedback in a pediatric resuscitation model of basic life support.

BACKGROUND: End-tidal carbon dioxide (ETCO2) correlates with systemic blood flow and resuscitation rate during cardiopulmonary resuscitation (CPR) and may potentially direct chest compression performance. We compared ETCO2-directed chest compressions with chest compressions optimized to pediatric basic life support guidelines in an infant swine model to determine the effect on rate of return of spontaneous circulation (ROSC). METHODS AND RESULTS: Forty 2-kg piglets underwent general anesthesia, tracheostomy, placement of vascular catheters, ventricular fibrillation, and 90 seconds of no-flow before receiving 10 or 12 minutes of pediatric basic life support. In the optimized group, chest compressions were optimized by marker, video, and verbal feedback to obtain American Heart Association-recommended depth and rate. In the ETCO2-directed group, compression depth, rate, and hand position were modified to obtain a maximal ETCO2 without video or verbal feedback. After the interval of pediatric basic life support, external defibrillation and intravenous epinephrine were administered for another 10 minutes of CPR or until ROSC. Mean ETCO2 at 10 minutes of CPR was 22.7±7.8 mm Hg in the optimized group (n=20) and 28.5±7.0 mm Hg in the ETCO2-directed group (n=20; P=0.02). Despite higher ETCO2 and mean arterial pressure in the latter group, ROSC rates were similar: 13 of 20 (65%; optimized) and 14 of 20 (70%; ETCO2 directed). The best predictor of ROSC was systemic perfusion pressure. Defibrillation attempts, epinephrine doses required, and CPR-related injuries were similar between groups. CONCLUSIONS: The use of ETCO2-directed chest compressions is a novel guided approach to resuscitation that can be as effective as standard CPR optimized with marker, video, and verbal feedback.

Retinopathy of prematurity in the Dominican Republic: challenges to screening and prevention.

OBJECTIVE: To determine the incidence of retinopathy of prematurity (ROP) in an intensive care nursery in the Dominican Republic and to identify factors that impact ROP outcomes, screening, and treatment. STUDY DESIGN: A database analysis was performed. The database was prospectively created by the pediatric ophthalmologist in a public maternity hospital in Santo Domingo during 2009. From January to December, all infants (n = 234) who received at least one ophthalmologic examination for ROP were included. ROP screening criteria were based upon: (1) American Academy of Pediatrics guidelines and (2) the presence of critical illness in larger, more mature infants at the discretion of the neonatologist. RESULTS: Overall, 22% were diagnosed with ROP and 4.3% had severe disease. Infants with ROP had a mean birth weight of 1452 g and a mean gestational age of 31 weeks, with 35% having a gestational age >32 weeks. In multivariable regression, only gestational age remained significant (0.8, 0.68 to 0.95). Twenty-two percent diagnosed with ROP did not complete all screening procedures. CONCLUSION: There are many challenges to preventing and treating ROP in the Dominican Republic. Increased awareness of the detrimental effects of hyperoxia, broader screening criteria, and an improved screening program will help to reduce visual impairment from ROP.

How does acculturation affect the use of complementary and alternative medicine providers among Mexican- and Asian-Americans?

Researchers have found that immigrants in the United States gradually relinquish cultural practices and adopt health behaviors similar to native born individuals as they acculturate. Few studies have looked at acculturation and Complementary and Alternative Medicine (CAM) use, particularly ethnic forms of CAM. This study uses data from the 2001 California Health Interview Survey-Complementary and Alternative Medicine (CHIS-CAM) supplement to estimate the prevalence of CAM provider use among Mexican- and Asian- Americans and examine the relationship of acculturation on use. Multinomial logistic regression models were used to predict the probability of provider use based on socio-demographic variables, health status and acculturation. Mexican- and Asian- Americans who have spent more time in the US were more likely to use chiropractors or massage therapists compared to no CAM provider. Both groups were less likely to use ethnic-specific CAM providers with more time in the US compared to chiropractors or massage therapists.

Sensory phenomena in obsessive-compulsive disorder and tic disorders: a review of the literature.

INTRODUCTION: A variety of subjective experiences have been reported to be associated with the symptom expression of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). First described in TS patients, these subjective experiences have been defined in different ways. There is no consensus in the literature on how to best define subjective experiences. This lack of consensus may hinder the understanding of study results and prevents the possibility of including them in the search for etiological factors associated with OCD and TS. METHODS: The objective of this article was to review the descriptions of subjective experiences in the English-language literature from 1980-2007. This meta-analytic review was carried out using the English-language literature from 1980-2007 available on MEDLINE, PsycINFO, and the Cochrane Library databases using the following search terms: premonitory urges, sensory tics, "just-right" perceptions, sensory phenomena, sensory experiences, incompleteness, "not just-right" phenomena, obsessive-compulsive disorder and TS, including OCD and/or TS, in all combination searches. We also searched for the references cited in each article previously found that referred to the aforementioned terms. Thirty-one articles were included in the study. RESULTS: Subjective experiences, in particular, the sensory phenomena, were important phenotypic variables in the characterization of the tic-related OCD subtype and were more frequent in the early-onset OCD subtype. There is a paucity of studies using structured interviews to assess sensory phenomena, their epidemiology and the etiological mechanisms associated with sensory phenomena. CONCLUSION: The current review provides some evidence that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.

Performance of delayed-enhancement magnetic resonance imaging with gadoversetamide contrast for the detection and assessment of myocardial infarction: an international, multicenter, double-blinded, randomized trial.

BACKGROUND: The identification and assessment of myocardial infarction (MI) are important for therapeutic and prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance of delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast for the detection of MI in an international, multicenter trial. METHODS AND RESULTS: Patients with their first MI were enrolled in an acute (< or = 16 days after MI; n=282) or chronic (17 days to 6 months; n=284) arm and then randomized to 1 of 4 doses of gadoversetamide: 0.05, 0.1, 0.2, or 0.3 mmol/kg. Standard delayed-enhancement MRI was performed before contrast (control) and 10 and 30 minutes after gadoversetamide. For blinded analysis, precontrast and postcontrast MRIs were randomized and then scored for enhanced regions by 3 independent readers not associated with the study. The infarct-related artery perfusion territory was scored from x-ray angiograms separately. In total, 566 scans were performed in 26 centers using commercially available scanners from all major US/European vendors. All scans were included in the analysis. The sensitivity of MRI for detecting MI increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 94% (chronic) after contrast compared with 11% before contrast. Likewise, the accuracy of MRI for identifying MI location (compared with infarct-related artery perfusion territory) increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 91% (chronic) after contrast compared with 9% before contrast. For gadoversetamide doses > or = 0.2 mmol/kg, 10- and 30-minute images provided equal performance, and peak creatine kinase-MB levels correlated with MRI infarct size (P<0.0001). CONCLUSIONS: Gadoversetamide-enhanced MRI using doses of > or = 0.2 mmol/kg is effective in the detection and assessment of both acute and chronic MI. This study represents the first multicenter trial designed to evaluate an imaging approach for detecting MI.