Evaluating the efficacy of endotracheal and intranasal epinephrine administration in severely asphyxic bradycardic newborn lambs: a randomised preclinical study.

OBJECTIVE: Intravenous epinephrine administration is preferred during neonatal resuscitation, but may not always be rapidly administered due to lack of equipment or trained staff. We aimed to compare the time to return of spontaneous circulation (ROSC) and post-ROSC haemodynamics between intravenous, endotracheal (ET) and intranasal (IN) epinephrine in severely asphyxic, bradycardic newborn lambs. METHODS: After instrumentation, severe asphyxia (heart rate <60 bpm, blood pressure ~10 mm Hg) was induced by clamping the cord in near-term lambs. Resuscitation was initiated with ventilation followed by chest compressions. Lambs were randomly assigned to receive intravenous (0.02 mg/kg), ET (0.1 mg/kg) or IN (0.1 mg/kg) epinephrine. If ROSC was not achieved after three allocated treatment doses, rescue intravenous epinephrine was administered. After ROSC, lambs were ventilated for 60 min. RESULTS: ROSC in response to allocated treatment occurred in 8/8 (100%) intravenous lambs, 4/7 (57%) ET lambs and 5/7 (71%) IN lambs. Mean (SD) time to ROSC was 173 (32) seconds in the intravenous group, 360 (211) seconds in the ET group and 401 (175) seconds in the IN group (p<0.05 intravenous vs IN). Blood pressure and cerebral oxygen delivery were highest in the intravenous group immediately post-ROSC (p<0.05), whereas the ET group sustained the highest blood pressure over the 60-min observation (p<0.05). CONCLUSION: Our study supports neonatal resuscitation guidelines, highlighting intravenous administration as the most effective route for epinephrine. ET and IN epinephrine should only be considered when intravenous access is delayed or not feasible.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype.

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

The Interplay Between Health Disparities and Acceptability of Virtual Reality: A Survey Study.

Virtual reality (VR) has emerged as a nonpharmacological adjuvant to manage acute and chronic pain symptoms. The goal of this survey study was to determine the acceptability of VR among chronic pain participants hailing from distressed and prosperous neighborhoods in the state of Maryland. We hypothesized that pain severity and interference vary in groups experiencing health disparities, potentially influencing VR's acceptability. From March 11 to March 15, 2020, we surveyed a cohort of clinically phenotyped participants suffering from chronic orofacial pain. Participants were asked to express their willingness to participate in a longitudinal VR study and their expectation of pain relief from using VR. Seventy out of 350 participants with chronic pain completed the survey (response rate: 20%). There was no difference in the likelihood of responding to the survey based on their neighborhood distress. Among survey respondents and nonrespondents, similar proportions of participants were from distressed neighborhoods. Among the respondents, 63 (90%) and 59 (84.3%) were willing to participate and expected to experience pain relief from the VR intervention, respectively. Age, sex, race, neighborhood distress, severity of pain, and prior VR experience did not influence willingness to participate in the VR trial or the expectations of VR-induced improvement. These findings suggest that VR as an adjuvant intervention is potentially accepted by chronic pain participants, irrespective of neighborhood-level social determinants of health.

The synergistic effects of mechanical ventilation and intrauterine inflammation on cerebral inflammation in preterm fetal sheep.

Background: Intrauterine inflammation and the requirement for mechanical ventilation independently increase the risk of perinatal brain injury and adverse neurodevelopmental outcomes. We aimed to investigate the effects of mechanical ventilation for 24 h, with and without prior exposure to intrauterine inflammation, on markers of brain inflammation and injury in the preterm sheep brain. Methods: Chronically instrumented fetal sheep at ~115 days of gestation were randomly allocated to receive a single intratracheal dose of 1 mg lipopolysaccharide (LPS) or isovolumetric saline, then further randomly allocated 1 h after to receive mechanical ventilation with room air or no mechanical ventilation (unventilated control + saline [UVC, n = 7]; in utero mechanical ventilation + saline [VENT, n = 8], unventilated control + intratracheal LPS [UVC + LPS, n = 7]; in utero ventilation + intratracheal LPS [VENT + LPS, n = 7]). Serial fetal blood and plasma samples were collected throughout the experimental protocol for assessment of blood biochemistry and plasma interleukin (IL)-6 levels. After 24 h of mechanical ventilation, fetal brains were collected for RT-qPCR and immunohistochemical analyses. Results: LPS exposure increased numbers of microglia and upregulated pro-inflammatory related genes within the cortical gray matter (GM) and subcortical white matter (SCWM) (pLPS < 0.05). Mechanical ventilation alone increased astrocytic cell density in the periventricular white matter (PVWM) (pVENT = 0.03) but had no effect on pro-inflammatory gene expression. The combination of ventilation and LPS increased plasma IL-6 levels (p < 0.02 vs. UVC and VENT groups), and exacerbated expression of pro-inflammatory-related genes (IL1ß, TLR4, PTGS2, CXCL10) and microglial density (p < 0.05 vs. VENT). Conclusion: This study demonstrates that 24 h of mechanical ventilation after exposure to intrauterine inflammation increased markers of systemic and brain inflammation and led to the upregulation of pro-inflammatory genes in the white matter. We conclude that 24 h of mechanical ventilation following intrauterine inflammation may precondition the preterm brain toward being more susceptible to inflammation-induced injury.

The CryoEM structure of human serum albumin in complex with ligands.

Human serum albumin (HSA) is the most prevalent plasma protein in the human body, accounting for 60 % of the total plasma protein. HSA plays a major pharmacokinetic function, serving as a facilitator in the distribution of endobiotics and xenobiotics within the organism. In this paper we report the cryoEM structures of HSA in the apo form and in complex with two ligands (salicylic acid and teniposide) at a resolution of 3.5, 3.7 and 3.4 Å, respectively. We expand upon previously published work and further demonstrate that sub-4 Å maps of ∼60 kDa proteins can be routinely obtained using a 200 kV microscope, employing standard workflows. Most importantly, these maps allowed for the identification of small molecule ligands, emphasizing the practical applicability of this methodology and providing a starting point for subsequent computational modeling and in silico optimization.

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs.

BACKGROUND: Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses. METHODS: At 119-120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3-4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit. RESULTS: LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte "end feet" vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS. CONCLUSION: LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Assessment of the changes in product characteristics, total ascorbic acid, total flavonoid content, total polyphenol content and antioxidant activity of dried soursop fruit tea (Annona muricata L.) during product storage.

Soursop (Annona muricata L.) fruit tea is a health-beneficial product that promotes economic development and addresses the issue of excessive agricultural waste. Prolonging the shelf-life of soursop fruit tea has been of scientific interest currently. This study evaluated the effects of three types of packaging materials of soursop fruit tea (e.g., paper, paper-combined Polyetylen (PE), and aluminum-combined PE) and different storage temperatures (5, 15, 30, and 45°C) on various product characteristics, total polyphenol content (TPC), total flavonoid content (TFC), total ascorbic acid (TAA), and 2,2-diphenyl-1-picryl hydrazyl (DPPH)/2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging capacity during 4 weeks of storage. The results revealed that the sample stored in aluminum-combined PE packaging at 30°C retained most of the product's characteristics and nutritional values. This was evidenced by the moisture content of 2.49%, TAA of 3.9 ± 1.4 mg/100 g dry weight, TPC of 12.89 ± 0.47 mgGAE/g, TFC of 0.54 ± 0.004 mgQE/g, DPPH scavenging activity of 4.06 ± 0.02 mgAA/g, and ABTS scavenging activity of 13.34 ± 0.32 mgAA/g. Additionally, the microbiological quality of the sample met the standard of TCVN 9740:2013. Overall, the study highlights the importance of packaging materials and storage temperatures to maintain the nutritional quality of soursop fruit tea. It provides valuable insights into the suitable storage conditions for preserving the quality and health-promoting effects of this product.

High-Resolution Cryo-Electron Microscopy Structure Determination of Haemophilus influenzae Tellurite-Resistance Protein A via 200 kV Transmission Electron Microscopy.

Membrane proteins constitute about 20% of the human proteome and play crucial roles in cellular functions. However, a complete understanding of their structure and function is limited by their hydrophobic nature, which poses significant challenges in purification and stabilization. Detergents, essential in the isolation process, risk destabilizing or altering the proteins' native conformations, thus affecting stability and functionality. This study leverages single-particle cryo-electron microscopy to elucidate the structural nuances of membrane proteins, focusing on the SLAC1 bacterial homolog from Haemophilus influenzae (HiTehA) purified with diverse detergents, including n-dodecyl ß-D-maltopyranoside (DDM), glycodiosgenin (GDN), ß-D-octyl-glucoside (OG), and lauryl maltose neopentyl glycol (LMNG). This research not only contributes to the understanding of membrane protein structures but also addresses detergent effects on protein purification. By showcasing that the overall structural integrity of the channel is preserved, our study underscores the intricate interplay between proteins and detergents, offering insightful implications for drug design and membrane biology.

In utero ventilation induces lung parenchymal and vascular alterations in extremely preterm fetal sheep.

Extremely preterm infants are often exposed to long durations of mechanical ventilation to facilitate gas exchange, resulting in ventilation-induced lung injury (VILI). New lung protective strategies utilizing noninvasive ventilation or low tidal volumes are now common but have not reduced rates of bronchopulmonary dysplasia. We aimed to determine the effect of 24 h of low tidal volume ventilation on the immature lung by ventilating preterm fetal sheep in utero. Preterm fetal sheep at 110 ± 1(SD) days' gestation underwent sterile surgery for instrumentation with a tracheal loop to enable in utero mechanical ventilation (IUV). At 112 ± 1 days' gestation, fetuses received either in utero mechanical ventilation (IUV, n = 10) targeting 3-5 mL/kg for 24 h, or no ventilation (CONT, n = 9). At necropsy, fetal lungs were collected to assess molecular and histological markers of lung inflammation and injury. IUV significantly increased lung mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) compared with CONT, and increased surfactant protein (SP)-A1, SP-B, and SP-C mRNA expression compared with CONT. IUV produced modest structural changes to the airways, including reduced parenchymal collagen and myofibroblast density. IUV increased pulmonary arteriole thickness compared with CONT but did not alter overall elastin or collagen content within the vasculature. In utero ventilation of an extremely preterm lung, even at low tidal volumes, induces lung inflammation and injury to the airways and vasculature. In utero ventilation may be an important model to isolate the confounding mechanisms of VILI to develop effective therapies for preterm infants requiring prolonged respiratory support.NEW & NOTEWORTHY Preterm infants often require prolonged respiratory support, but the relative contribution of ventilation to the development of lung injury is difficult to isolate. In utero mechanical ventilation allows for mechanistic investigations into ventilation-induced lung injury without confounding factors associated with sustaining extremely preterm lambs ex utero. Twenty-four hours of in utero ventilation, even at low tidal volumes, increased lung inflammation and surfactant protein expression and produced structural changes to the lung parenchyma and vasculature.

Mechanical ventilation induces brainstem inflammation in preterm fetal sheep.

Background: Preterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep. Methods: Preterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury. Results: In utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups. Conclusion: Mechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.

Rent affordability after hurricanes: Longitudinal evidence from US coastal states.

Climate change is expected to increase the frequency and intensity of natural hazards such as hurricanes. With a severe shortage of affordable housing in the United States, renters may be uniquely vulnerable to disaster-related housing disruptions due to increased hazard exposure, physical vulnerability of structures, and socioeconomic disadvantage. In this work, we construct a panel dataset consisting of housing, socioeconomic, and hurricane disaster data from counties in 19 states across the East and Gulf Coasts of the United States from 2009 to 2018 to investigate how the frequency and intensity of a hurricane correspond to changes in median rent and housing affordability (the interaction between rent prices and income) over time. Using a two-stage least square random-effects regression model, we find that more intense prior-year hurricanes correspond to increases in median rents via declines in housing availability. The relationship between hurricanes and rent affordability is more complex, though the occurrence of a hurricane in a given year or the previous year reduces affordable rental housing, especially for counties with higher percentages of renters and people of color. Our results highlight the multiple challenges that renters are likely to face following a hurricane, and we emphasize that disaster recovery in short- and medium-term should focus on providing safe, stable, and affordable rental housing assistance.

A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials.

BACKGROUND: Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential. METHODS: We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690). RESULTS: Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias. CONCLUSION: Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation.

Developing mango powders by foam mat drying technology.

Using mango purée from overripe mangoes to produce powders helped to solve agricultural product stagnation. The research investigates the effect of thickening additives, convection drying, and heat pump drying on bioactive compounds such as total phenolic content (TPC), total flavonoid content (TFC), color, and solubility of the final product. The obtained results showed that the mixture (gum arabic and maltodextrin in the ratio 50:50 w/w) at a concentration of 15% gave a good quality powder texture when dried by hot air convection at 55°C with TPC (21.24 ± 1.58 mg GAE/g dry weight [DW]) and TFC (0.34 ± 0.02 mg QE/g DW), respectively. In addition, the product has a high solubility of 64.35%, with the highest pass-through point of 17.11.

Creatine in the fetal brain: A regional investigation of acute global hypoxia and creatine supplementation in a translational fetal sheep model.

Background: Creatine supplementation during pregnancy is a promising prophylactic treatment for perinatal hypoxic brain injury. Previously, in near-term sheep we have shown that fetal creatine supplementation reduces cerebral metabolic and oxidative stress induced by acute global hypoxia. This study investigated the effects of acute hypoxia with or without fetal creatine supplementation on neuropathology in multiple brain regions. Methods: Near-term fetal sheep were administered continuous intravenous infusion of either creatine (6 mg kg-1 h-1) or isovolumetric saline from 122 to 134 days gestational age (dGA; term is approx. 145 dGA). At 131 dGA, global hypoxia was induced by a 10 min umbilical cord occlusion (UCO). Fetuses were then recovered for 72 h at which time (134 dGA) cerebral tissue was collected for either RT-qPCR or immunohistochemistry analyses. Results: UCO resulted in mild injury to the cortical gray matter, thalamus and hippocampus, with increased cell death and astrogliosis and downregulation of genes involved in regulating injury responses, vasculature development and mitochondrial integrity. Creatine supplementation reduced astrogliosis within the corpus callosum but did not ameliorate any other gene expression or histopathological changes induced by hypoxia. Of importance, effects of creatine supplementation on gene expression irrespective of hypoxia, including increased expression of anti-apoptotic (BCL-2) and pro-inflammatory (e.g., MPO, TNFa, IL-6, IL-1ß) genes, particularly in the gray matter, hippocampus, and striatum were identified. Creatine treatment also effected oligodendrocyte maturation and myelination in white matter regions. Conclusion: While supplementation did not rescue mild neuropathology caused by UCO, creatine did result in gene expression changes that may influence in utero cerebral development.

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Impacts of COVID-19 crisis and some related factors on the mental health of 37150 Vietnamese students: a cross-sectional online study.

BACKGROUND: University students are vulnerable to changes due to COVID-19 pandemic. Although warning has been made about the impact of this crisis on students' mental health, there are barely any sufficient study. This work investigated how the pandemic affected the mental health of students at the Vietnam National University of Ho Chi Minh City (VNU-HCMC) and efficiency of available mental health supportive methods. METHODS: An online survey was conducted among students at Vietnam National University of Ho Chi Minh City (VNU-HCMC) from October 18, 2021, to October 25, 2021. Microsoft Excel 16.51 (Microsoft, USA) and R language, Epi packages 2.44 and 4.1.1 (rdrr.io) were used for data analysis. RESULTS: Thirty-seven thousand one hundred fifty students participated in the survey, including 48.4% female and 51.6% male. Online learning pressure was mainly recorded (65.1%). Many students suffered from sleeping disorders (56.2%). Some reported being victims of abuse (5.9%). Female students expressed a significantly higher level of distress than males, particularly the feeling of ambiguity about the purpose of life (p-value < 0.0001, OR: 0.94, 95% CI: [0.95-0.98]). Third-year students suffered higher stress levels than others, especially in online learning (68.8%, p-value < 0.05). Mental health statuses among students of different lockdown status regions were not significantly different. Therefore, lockdown status did not affect the stress levels of students which suggested that poor mental health outcomes seemed to root in the suspension of everyday university life rather than the prohibition of going out. CONCLUSIONS: During COVID-19, students experienced lots of stress and mental problems. These findings underscore the importance of academic and innovative activities, bringing attention to the needs of interactive study and extra-curricular activities.

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs is enhanced following sildenafil and inhaled nitric oxide administration.

Background: Neurovascular coupling (NVC) leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity and metabolic demand. Impaired or immature NVC reported in the preterm brain, potentially reduces cerebral oxygenation following increased neural activity, predisposing to cerebral tissue hypoxia. Endogenous nitric oxide (NO) is a potent vasodilator and a major mediator of NVC and the cerebral haemodynamic response. NO modulators, such as inhaled nitric oxide (iNO) and sildenafil, induce vasodilation and are used clinically to treat pulmonary hypertension in preterm neonates. However, their impact on NVC in the preterm brain are unknown. We aimed to characterise the cerebral functional haemodynamic response in the preterm brain exposed to NO modulators. We hypothesized that iNO and sildenafil in clinical dosages would increase the baseline cerebral perfusion and the cerebral haemodynamic response to neural activation. Methods: Preterm lambs (126-7 days' gestation) were delivered and mechanically ventilated. The cerebral functional haemodynamic response was measured using near infrared spectroscopy as changes in cerebral oxy- and deoxyhaemoglobin (ΔoxyHb, ΔdeoxyHb), following left median nerve stimulations of 1.8, 4.8, and 7.8 s durations in control preterm lambs (n = 11), and following 4.8 and 7.8 s stimulations in preterm lambs receiving either sildenafil citrate (n = 6, 1.33 mcg/kg/hr) or iNO (n = 8, 20 ppm). Results: Following 1.8, 4.8, and 7.8 s stimulations, ∆oxyHb in the contralateral cortex increased (positive functional response) in 7/11 (64%), 7/11 (64%), and 4/11 (36%) control lambs respectively (p < 0.05). Remaining lambs showed decreased ΔoxyHb (negative functional response). Following 4.8 s stimulations, more lambs receiving sildenafil or iNO (83% and 100% respectively) showed positive functional response compared to the controls (p < 0.05). No significant difference between the three groups was observed at 7.8 s stimulations. Conclusion: In the preterm brain, prolonged somatosensory stimulations increased the incidence of negative functional responses with decreased cerebral oxygenation, suggesting that cerebral oxygen delivery may not match the oxygen demand. Sildenafil and iNO increased the incidence of positive functional responses, potentially enhancing NVC, and cerebral oxygenation.