Cooling Under a Blanketrol System Versus Cooling With an Arctic Sun Thermoregulation System (CATS) for Neonates Undergoing Therapeutic Hypothermia.

Background Despite evidence suggesting improved outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), data on the impact of temperature variability during cooling and its association with clinical outcomes remain limited. Objective To compare the efficacy and ease of use of two different cooling systems, the Arctic Sun (Medivance, Inc., Louisville, CO) vs. the Blanketrol III (Gentherm Medical, Cincinnati, OH) on achieving TH, temperature variability, and clinical outcomes in neonates with HIE undergoing TH. Methods This study was conducted at the Baylor Scott and White Medical Center's Level IV NICU. The study employed a retrospective cohort design, comparing infants treated with the Arctic Sun device (from December 2020 to August 2021) to a historical cohort treated with the Blanketrol system (from January 2017 to November 2020). Both groups were evaluated for clinical characteristics, patients' outcomes, and ease of use of the cooling devices. Ease of use was assessed through a self-developed survey administered to NICU nurses. Core body temperatures throughout the cooling course were documented at four-hour intervals, including induction, maintenance, and rewarming phases. Results Twenty-two infants were cooled using the Arctic Sun system, and 44 infants were cooled with the Blanketrol device. Median birth weight and gestational age were comparable. There were no significant differences in one-minute and five-minute appearance, pulse, grimace, activity, and respiration (APGAR) scores. The Arctic Sun group had a significantly higher rate of maternal morbidities, including diabetes and placental abruption. Although the median temperature achieved with both devices was 33.5°C, temperature variability was significantly greater with the Blanketrol device (p = 0.03). Thrombocytopenia rates were statistically different between the groups (9% in Arctic Sun vs. 38% in Blanketrol, p = 0.001). Although the Blanketrol group had higher rates of disseminated intravascular coagulation (48% vs. 37%), hypercalcemia (23% vs. 5%), and subcutaneous fat necrosis (7% vs. 5%), these differences were not statistically significant. A nurses' survey on ease of use revealed a strong preference for the Arctic Sun cooling system. Over 85% of nurses found it easier to learn and set up and required less manual intervention than the Blanketrol device. Conclusions Gel adhesive pad-based TH is a potentially superior modality to traditional water-circulating cooling devices. These pads offer advantages in user-friendliness, improved temperature control precision, and potentially reduced adverse event profiles.

Pre-Medications for Non-Emergency Tracheal Intubation in the United States Neonatal Intensive Care Units.

BACKGROUND: Premedication in neonates undergoing elective intubation effectively minimizes the negative physiological events of bradycardia, systemic hypertension, intracranial hypertension, and hypoxia. Premedication decreases procedure-related pain and discomfort. This study aimed to evaluate the current practice of pre-intubation medications for non-emergent intubations in preterm and term neonates in the United States. STUDY DESIGN: A cross-sectional survey (Appendix) was sent via e-mail to all level 3 and 4 Neonatal Intensive Care Units (NICUs) of the Organization of Neonatal Perinatal Medicine Training Program Directors (ONTPD), NICU directors with pediatric residency only, and Baylor Scott and White Health, Mednax, and Envision health services systems. RESULTS: Of 170 responses, 41% (69/168) routinely premedicate, 38% (64/168) premedicate under specific circumstances, and 21% (35/168) do not administer any routine pre-intubation medications. Only 46% (77/168) of units had a written policy. The most frequently used drugs were fentanyl (68%, 116/170), atropine (39%, 66/170), midazolam (38%, 64/170), and morphine (26%, 45/170). 21% (36/170) used a two-drug combination, and 38% (64/170) used a three-drug combination. The most commonly used two-drug combination was atropine and fentanyl, and the most common three-drug combination was atropine, fentanyl, and a paralytic agent. CONCLUSION:  Despite the well-documented benefits of premedication for NICU intubations, as aligned with AAP recommendations, the US lags behind other nations, with stagnant rates since 2006. This disparity persists despite a rise in written policies, which exhibit significant content variations. The authors advocate for the adoption of standardized, AAP-aligned policies across all NICUs in the US. Continued research is vital to monitor the progress of this crucial practice and address any underlying barriers to implementation.

Evaluation of Autism Spectrum Disorder Risk in Infants With Intraventricular Hemorrhage.

Background This study evaluates the long-term risk of autism spectrum disorder (ASD) in infants with intraventricular hemorrhage (IVH) using the Modified Checklist for Autism in Toddlers-Revised with Follow-Up (M-CHAT-R/F) screening tool. Methods This retrospective cohort study compared IVH (exposed) infants across all gestational age groups with no-IVH (non-exposed) infants admitted to level IV neonatal intensive care unit (NICU). The M-CHAT-R/F screening tool was used to assess the ASD risk at 16-30 months of age. Discharge cranial ultrasound (CUS) findings also determined the ASD risk. Descriptive statistics comprised median and interquartile range for skewed continuous data and frequencies and percentages for categorical variables. Comparisons for non-ordinal categorical measures in bivariate analysis were carried out using the χ2 test or Fisher exact test. Results Of the 334 infants, 167 had IVH, and 167 had no IVH. High ASD risk (43% vs. 20%, p = 0.044) and cerebral palsy (19% vs. 5%, p = 0.004) were significantly associated with severe IVH. Infants with CUS findings of periventricular leukomalacia had 3.24 odds of developing high ASD risk (odds ratios/OR: 3.24, 95% confidence interval/CI: 0.73-14.34), and those with hydrocephalus needing ventriculoperitoneal (VP) shunt had 4.75 odds of developing high ASD risk (OR: 4.75, 95% CI: 0.73-30.69). Conclusion Severe IVH, but not mild IVH, increased the risk of ASD and cerebral palsy. This study demonstrates the need for timely screening for ASD in high-risk infants. Prompt detection leads to earlier treatment and better outcomes.

Comparison of clinical outcomes and biochemical markers in normal and preeclamptic pregnancies: a prospective cohort study.

Background: Preeclampsia (PreE), the de novo onset of hypertension and proteinuria at 20 weeks of gestation, is a leading cause of maternal and fetal morbidity and mortality. This study compared inflammatory biomarkers in PreE and normal pregnancies using paired samples of mothers and neonates. Methods: Twenty normal pregnant and 27 PreE patients were monitored for biomarkers, neonatal outcomes, and placental morphologies. Fetal and maternal serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble endoglin (sENG), and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured by enzyme-linked immunosorbent assay. Results: Placental thickness was 25 mm in early PreE subjects compared to 32 mm in late PreE subjects (P < 0.05). Placental volume was 296 cm3 in early PreE compared to 393 cm3 in late PreE (P < 0.05). The average hospital stay for PreE babies was longer (20 ± 5 days) compared to babies from normal pregnancies (2 ± 1 days; P < 0.05). PreE babies had a lower Ponderal index (2.28 ± 0.3) than those from normal pregnancies (2.95 ± 0.2; P < 0.05). sENG and sFLT-1 had cord values like the maternal values, while VEGF and PlGF did not. Conclusion: PreE alters the intrauterine environment by activating chemical mediators that result in maternal and fetal complications.

Influenza Vaccine Effectiveness Among Children: 2011-2020.

BACKGROUND AND OBJECTIVES: Infants and children are at increased risk of severe influenza virus infection and its complications. Influenza vaccine effectiveness (VE) varies by age, influenza season, and influenza virus type/subtype. This study's objective was to examine the effectiveness of inactivated influenza vaccine against outpatient influenza illness in the pediatric population over 9 influenza seasons after the 2009 A(H1N1) pandemic. METHODS: During the 2011-2012 through the 2019-2020 influenza seasons at outpatient clinics at 5 sites of the US Influenza Vaccine Effectiveness Network, children aged 6 months to 17 years with an acute respiratory illness were tested for influenza using real-time, reverse-transcriptase polymerase chain reaction. Vaccine effectiveness was estimated using a test-negative design. RESULTS: Among 24 148 enrolled children, 28% overall tested positive for influenza, 3017 tested positive for influenza A(H3N2), 1459 for influenza A(H1N1)pdm09, and 2178 for influenza B. Among all enrollees, 39% overall were vaccinated, with 29% of influenza cases and 43% of influenza-negative controls vaccinated. Across all influenza seasons, the pooled VE for any influenza was 46% (95% confidence interval, 43-50). Overall and by type/subtype, VE against influenza illness was highest among children in the 6- to 59-month age group compared with older pediatric age groups. VE was lowest for influenza A(H3N2) virus infection. CONCLUSIONS: Analysis of multiple seasons suggested substantial benefit against outpatient illness. Investigation of host-specific or virus-related mechanisms that may result in differences by age and virus type/subtype may help further efforts to promote increased vaccination coverage and other influenza-related preventative measures.

Maternal preeclampsia as a risk factor for developing bronchopulmonary dysplasia in neonates.

OBJECTIVE: To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. MAIN OUTCOME MEASURE: The primary outcome was BPD incidence. RESULTS: 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). CONCLUSIONS: Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

Influenza vaccination coverage among persons seeking outpatient medical care for acute respiratory illness in five states in the United States, 2011-2012 through 2018-2019.

BACKGROUND: In the United States (U.S.), annual influenza vaccination has been recommended for all persons aged ≥6 months with the Healthy People 2020 coverage target of 70%. However, vaccination coverage has remained around 42-49% during the past eight influenza seasons. We sought to quantify influenza vaccination coverage and factors associated with vaccination in persons seeking outpatient medical care for an acute respiratory illness (ARI). METHODS: We enrolled outpatients aged ≥6 months with ARI from >50 U.S. clinics from 2011 to 2012 through 2018-2019 influenza seasons and tested for influenza with molecular assays. Vaccination status was based on documented receipt of the current season's influenza vaccine. We estimated vaccination coverage among influenza-negative study participants by study site, age, and season, and compared to state-level influenza coverage estimates in the general population based on annual immunization surveys. We used multivariable logistic regression to examine factors independently associated with receipt of influenza vaccines. RESULTS: We enrolled 45,424 study participants with ARI who tested negative for influenza during the study period. Annual vaccination coverage among influenza-negative ARI patients and the general population in the participating states averaged 55% (range: 47-62%), and 52% (range: 46-54%), respectively. Among enrollees, coverage was highest among adults aged ≥65 years (82%; range, 80-85%) and lowest among adolescents aged 13-17 years (38%; range, 35-41%). Factors significantly associated with non-vaccination included non-White race, no college degree, exposure to cigarette smoke, absence of high-risk conditions, and not receiving prior season influenza vaccine. CONCLUSIONS: Influenza vaccination coverage over eight seasons among outpatients with non-influenza respiratory illness was slightly higher than coverage in the general population but 15% lower than national targets. Increased efforts to promote vaccination especially in groups with lower coverage are warranted to attain optimal health benefits of influenza vaccine.

Proteomics and Metabolomics in Pregnancy-An Overview.

IMPORTANCE: Pregnancy is getting more and more complex due to increasing number of complications that may affect fetal outcomes. The introduction of newer "proteomics and metabolomics" technologies in the field of obstetrics and gynecology may allow physicians to identify possible associated etiologies that affect the mother during pregnancy and lead to associated complications affecting the offspring. OBJECTIVE: The principal objective of this review article is to provide a comprehensive evaluation of the use of proteomics and metabolomics in complicated pregnancies. Future studies that incorporate data from multiple technologies may allow the development of an integrated biological system approach to maternal genomes, proteomes, and metabolomes in pregnancy. EVIDENCE ACQUISITION AND RESULTS: We conducted a substantial MEDLINE, EBSCOhost, and Cochrane database search for all the relevant articles containing use of "omics" technologies in pregnancy. We identified 197 relevant articles, following standardized systematic review process along with grading systems; 69 eligible articles were identified. CONCLUSION/RELEVANCE: We sought to provide a comprehensive review in this emerging field of "omics" in pregnancy and associated complications. This article focuses mainly on use of proteomics and metabolomics identification techniques and possible interventions for early pregnancy complications to improve neonatal outcomes.

The Tri-phasic Role of Hydrogen Peroxide in Blood-Brain Barrier Endothelial cells.

Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 µM to 1 µM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 µM and above induced monolayer hyperpermeability significantly (p < 0.05). H2O2 at 10 mM and above decreased cell viability and induced apoptosis (p < 0.05). There was a decrease of ZO-1 tight junction localization with 100 µm H2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 µm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.

Diabetes and pre-eclampsia affecting pregnancy: a retrospective cross-sectional study.

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan's post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.

Congenital midline nasal anomalies.

Congenital midline nasal anomalies are rare, with a prevalence of 1 in 20,000 to 40,000 births and with 5% to 7% of them being nasal glioma. Differential diagnoses of nasal anomalies include nasal dermoid cysts, gliomas, encephaloceles, nasal polyps, and some other rare anomalies. Due to current medical technological advancements, most of these anomalies are easily correctable, though delaying management may lead to fatal effects. This report describes two cases-one of nasal glioma and one of nevus lipomatosus cutaneous superficialis-that presented as respiratory distress in a newborn. Approximately 10 to 20 cases of these two conditions have been described; notably, this is the second documented case of nevus lipomatosus cutaneous superficialis with nasal presentation.

Multicenter neonatal databases: Trends in research uses.

BACKGROUND: In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. METHODS: We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. RESULTS: A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. CONCLUSIONS: Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.

Attenuation of Blood-Brain Barrier Breakdown and Hyperpermeability by Calpain Inhibition.

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1ß (IL-1ß) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain. In these studies, rat brain microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated attenuation of IL-1ß-induced monolayer hyperpermeability. Calpain inhibition led to protection against IL-1ß-induced loss of zonula occludens-1 (ZO-1) at the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1ß treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain inhibition via calpain inhibitor III and calpastatin decreased IL-1ß-induced calpain activity significantly (p < 0.05). IL-1ß had no detectable effect on intracellular calcium mobilization or endothelial cell viability. Furthermore, calpain inhibition preserved BBB integrity/permeability in a mouse controlled cortical impact model of TBI when studied using Evans blue assay and intravital microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL-1ß-induced loss of BBB integrity and permeability by altering tight junction integrity, promoting the displacement of ZO-1, and disorganization of cytoskeletal assembly. IL-1ß-mediated alterations in permeability are neither due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has beneficial effects against TBI-induced BBB hyperpermeability.

Bilateral congenital pseudoarthrosis of the clavicles in a newborn.

Bilateral congenital pseudoarthrosis of the clavicles is extremely rare. We report a case of this entity presenting in the neonatal period. We highlight the importance of the differential diagnosis when clavicular fracture shows no evidence of healing or occurs bilaterally.

Maternal pre-eclampsia as a risk factor for necrotizing enterocolitis.

OBJECTIVE: Similar pro-inflammatory responses are present in pre-eclampsia (PE) and necrotizing enterocolitis (NEC). We hypothesized that maternal PE is an independent risk factor for the development of NEC. METHODS: A retrospective database of all live births (2008-2011) at a tertiary center was constructed. Infant and maternal characteristics were gathered. Babies born to mothers with or without PE were compared. Data were analyzed using Mann-Whitney U, Pearson's χ(2), binary logistic regression and relative risks. RESULTS: Incidence of NEC was 1.5% in non-PE and 4.6% in the PE group (p < 0.001), but once controlled for gestational age and birth weight, the difference lost statistical significance. PE babies were more frequently preterm (41.4% versus 14.5%, p < 0.001) and had intrauterine growth restriction (IUGR) (10.2% versus 6.3%, p < 0.001). Within preterm babies, 9.0% of non-PE and 10.8% of PE babies developed NEC (p = 0.25). Effect of PE was significant in sub-group of IUGR babies, with NEC in 1.5% of non-PE and 13.6% in PE babies (p < 0.001). CONCLUSIONS: Maternal PE is an independent risk factor for the development of NEC in some sub-groups of babies, most notably with IUGR. Fetal hypoxia caused by abnormal placentation in PE leads to restricted growth, and may be the underlying mechanism that predisposes the newborn to NEC.

Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord.

OBJECTIVE: Preeclampsia (preE) has a significant link to alterations of placental function leading to stress and apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring. We assessed apoptotic signaling in placentas and umbilical cords from patients with and without preE. METHODS: We collected placental and cord tissues from 27 normal pregnant (NP) women and 20 preE consenting patients after delivery in an IRB approved prospective study. p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-apoptotic Bcl-2-associated X (Bax), anti-apoptotic Bcl-2, caspase-9, and pro-inflammatory cyclooxygenase-2 (Cox-2) were evaluated by western blot and immunohistochemistry. Comparisons were performed using Student's t-test. RESULTS: p38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold), ratio of Bax/Bcl-2 (Placenta: 1.7 fold, Cord: 2.2 fold), caspase-9 (Placenta: 1.5 fold, Cord: 1.8 fold) and Cox-2 (Placenta: 2.5 fold, Cord: 2.3 fold) were up-regulated (p < 0.05) in preE compared to NP patients. Average hospital stays for preE babies were longer than NP babies. No complications were reported for NP babies; however, all of preE babies had multiple complications. CONCLUSIONS: Apoptotic and stress signaling are augmented in preE placenta and cord tissue that alter the intrauterine environment and activates the detrimental signaling that is transported to fetus.

Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition.

Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1ß (IL-1ß) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1ß (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 µg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 µM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1ß-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1ß treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB hyperpermeability in a mouse model of TBI indicating its potential as a therapeutic agent for brain edema when established in humans.

Inflammation in Complicated Pregnancy and Its Outcome.

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.

Safety and efficacy of packed red blood cell transfusions at different doses in very low birth weight infants.

This double-blinded, randomized, crossover study evaluated the safety and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC transfusions, with a mean gestational age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant was randomized to receive one of two treatment sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants were monitored during and after transfusions, and the efficacy and safety of the treatments were evaluated. Infants had higher posttransfusion hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg transfusions. There were no differences in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion, high-volume PRBC transfusions (20 mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit levels but no adverse effects. Higher-volume transfusions may reduce the need for multiple transfusions and therefore the number of donors the infant is exposed to.

Neonatal Thrombocytopenia as a Consequence of Maternal Preeclampsia.

Introduction Preeclampsia (preE) is pregnancy-induced hypertension affecting a significant proportion of pregnant women worldwide and can cause detrimental effects in the mother and newborn. Some of the effects in the newborn include neonatal thrombocytopenia. Pertaining specifically to neonatal thrombocytopenia, several questions remain unanswered. Discussion According to the current literature, neonatal thrombocytopenia due to maternal preE is highly prevalent in the general population and the incidence is reported to be around 30% worldwide. This review gives an insight into the syndrome and summarizes the possible pathological mechanisms, the diagnostic approach, complications, and therapeutic interventions of neonatal thrombocytopenia. It also identifies the involvement of other cell lines, apart from platelets in the newborns. Furthermore, we suggest a future prospective study to investigate the pathogenesis of preE and plan a study involving animal models to come up with a possible therapeutic intervention to prevent preE and its various consequences in neonates.