Comparative efficacy of therapeutic plasma exchange and insulin in hypertriglyceridemia-induced acute pancreatitis.

INTRODUCTION: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents a therapeutic challenge with no currently definitive treatment, including therapeutic plasma exchange (TPE) and insulin. TPE aims to quickly reduce serum triglyceride (TG); however, its efficacy lacks convincing evidence. Intravenous insulin is a promising and convenient alternative, while comparative data is limited. METHODS: This retrospective, single-center study compared TPE and insulin treatment in HTG-AP patients. The primary outcome measured was the percentage of TG reduction within 48 hours of admission. RESULTS: The study included 33 TPE-treated and 56 insulin-treated patients. The TPE groups were more severe than those with medical therapy at baseline characteristics. A trend towards higher TG reduction within 24 hours was observed in the TPE group (62.5% [IQR 51.7-83.3] vs. 55.7% [IQR 34.2-74.7], p = 0.038). However, no significant difference in TG reduction at 48 hours was found between insulin and TPE groups (83.6% and 81.9%, respectively, p = 0.715). The TPE group exhibited extended hospital stays (10.0 [IQR 7.0-13.5] days vs. 6.0 [4.0-8.7] days, p = 0.001) without any difference in in-hospital mortality or time needed to lower TG below < 11.3 mmol/L. CONCLUSION: In patients with HTG-AP, TPE decreased plasma triglyceride levels faster in the first 24 hours than insulin therapy. However, there was no significant advantage after 48 hours. Therefore, insulin may be a promising alternative and convenient treatment in carefully selected patients with HTG-AP.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Waterpipe Tobacco Smoking and Risk of Cancer Mortality.

Importance: There has been an increasing trend of using noncigarette products, including waterpipe tobacco (WTP), worldwide. While cigarette smoking is a well-established risk factor for numerous cancers, little is known about the association between WTP smoking and cancer mortality. Objective: To assess the association between WTP smoking and risk of cancer mortality in Vietnam. Design, Setting, and Participants: This cohort study was based on data from the Hanoi Prospective Cohort Study, an ongoing study with a median (range) follow-up of 11.0 (0.1-11.6) years for participants aged 15 years or older in Northern Vietnam from 2007 through 2019. Data were analyzed from June 1 to September 1, 2023. Exposures: Tobacco smoking and WTP smoking statuses. Main Outcomes and Measures: Overall and site-specific cancer mortality. Cox proportional regression models were used to calculate the hazard ratio (HR) and 95% CIs for the associations between WTP smoking alone, cigarette smoking alone, and dual WTP and cigarette smoking and the risk of cancer death. Results: A total of 554 cancer deaths were identified among the 39 401 study participants (mean [SD] age, 40.4 [18.8] years; 20 616 females [52.3%]). In multivariable models, compared with never smokers, ever smokers had a significantly increased risk of cancer mortality (HR, 1.87; 95% CI, 1.48-2.35). Exclusive WTP smokers had the highest risk of cancer mortality compared with never smokers (HR, 2.66; 95% CI, 2.07-3.43). Risk of cancer mortality was higher for dual smokers of WTP and cigarettes (HR, 2.06; 95% CI, 1.53-2.76) than for exclusive cigarette smokers (HR, 1.86; 95% CI, 1.41-2.45). As most smokers (95.6% [8897 of 9312]) were male, these patterns were more apparent in male participants. Compared with never smokers, exclusive WTP smoking among males was associated with an elevated risk of death from liver cancer (HR, 3.92; 95% CI, 2.25-6.85), lung cancer (HR, 3.49; 95% CI, 2.08-5.88), nasopharyngeal carcinoma (HR, 2.79; 95% CI, 1.27-6.12), and stomach cancer (HR, 4.11; 95% CI, 2.04-8.27). For exclusive WTP smokers, the risk of cancer mortality was highest among those who smoked 11 to 15 sessions per day (HR, 3.42; 95% CI, 2.03-5.75), started smoking at age 26 to 30 years (HR, 4.01; 95% CI, 2.63-6.11), smoked for 9 to 20 years (HR, 4.04; 95% CI, 2.16-7.56), and smoked 61 to 160 sessions annually (HR, 3.68; 95% CI, 2.38-5.71). For males, the risk of cancer death was lower for those who had quit smoking for more than 10 years, compared with those who quit smoking within 1 year (HR, 0.27; 95% CI, 0.11-0.66; P for trend < .001). Conclusion and Relevance: In this cohort study in Vietnam, WTP smoking alone or in combination with cigarette smoking was associated with an increased risk of cancer death due to liver cancer, lung cancer, nasopharyngeal carcinoma, and stomach cancer. A tailored program to control WTP smoking is warranted in Vietnam and low- and middle-income countries with a high prevalence of smoking and modest resources to address smoking-related issues.

Floating treatment wetlands to improve the water quality of the Hang Bang canal, Ho Chi Minh City, Vietnam: Effect of plant species.

Floating treatment wetlands (FTWs) are artificial platforms that allow aquatic emergent plants to grow in water. Aquatic macrophytes and microorganisms attached to plant roots contribute to the remediation of the contaminated water through physicochemical and biological processes. The pollutant removal treatment performance is affected by various factors, including the plant species. In this study, several plant species, i.e. Canna generalis, Phragmites australis, Pennisetum purpureum, Cyperus alternifolius rottb, Kyllinga brevifolia rottb, and Cyperus ordoratus were investigated for their potential to clean-up water from the Hang Bang canal in Ho Chi Minh City (Vietnam). Canna generalis, Phragmites australis, and Cyperus alternifolius were found to be suitable for FTWs with the highest performance compared to that of other plant species investigated. The organic and nitrogen removal rates amounted to 48-70 g COD m-3 d-1 and 0.7-1.2 g N m-3 d-1, respectively, whereas the reduction of pathogens was around 1.86-3.00 log. Furthermore, FTW systems bring other benefits such as improving ecosystem functioning and biodiversity, producing value-added products from plant biomass, as well as attracting the attention of communities, thus increasing social acceptance of environmental technology interventions.

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.

Pembrolizumab-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis in a Vietnamese patient with nonsmall-cell lung cancer.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

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.

The Temporal Relationship between Blood-Brain Barrier Integrity and Microglial Response following Neonatal Hypoxia Ischemia.

Blood-brain barrier (BBB) dysfunction and neuroinflammation are key mechanisms of brain injury. We performed a time-course study following neonatal hypoxia-ischemia (HI) to characterize these events. HI brain injury was induced in postnatal day 10 rats by single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). At 6, 12, 24, and 72 h (h) post-HI, brains were collected to assess neuropathology and BBB dysfunction. A significant breakdown of the BBB was observed in the HI injury group compared to the sham group from 6 h in the cortex and hippocampus (p < 0.001), including a significant increase in albumin extravasation (p < 0.0033) and decrease in basal lamina integrity and tight-junction proteins. There was a decrease in resting microglia (p < 0.0001) transitioning to an intermediate state from as early as 6 h post-HI, with the intermediate microglia peaking at 12 h (p < 0.0001), which significantly correlated to the peak of microbleeds. Neonatal HI insult leads to significant brain injury over the first 72 h that is mediated by BBB disruption within 6 h and a transitioning state of the resident microglia. Key BBB events coincide with the appearance of the intermediate microglial state and this relationship warrants further research and may be a key target for therapeutic intervention.

Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. METHODS: We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. RESULTS: Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. CONCLUSION: Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

Phenotype of early-onset fetal growth restriction in sheep.

Introduction: Fetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development in utero and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment. We hypothesised that the trajectory of growth would be adversely impacted by FGR. Methods: FGR was induced via surgical placental insufficiency in fetal sheep (89 days gestation/0.6 gestation; n=135) and compared to age-matched controls over the last third of gestation and into neonatal life (n=153). Results: Body weight of FGR fetuses/lambs was significantly reduced compared to controls (p<0.0001) from 127 days of gestation (term is 148 days), with increased brain:body weight ratio (p<0.0001) indicative of brain sparing. All biometric measures of body size were reduced in the FGR group with the exception of biparietal (head) diameter. The trajectory of body growth in the last trimester of sheep pregnancy was significantly reduced in the FGR group compared to controls, and stillbirth rate increased with longer gestation. Discussion: This work provides a well characterised FGR animal model that mimics the known physiological adaptations in human pregnancy and can be used to determine the efficacy of potential interventions.

Immunosuppressive Cyclotides: A Promising Approach for Treating Autoimmune Diseases.

The immune system maintains constant surveillance to prevent the infiltration of both endogenous and exogenous threats into host organisms. The process is regulated by effector immune cells that combat external pathogens and regulatory immune cells that inhibit excessive internal body inflammation, ultimately establishing a state of homeostasis within the body. Disruption to this process could lead to autoimmunity, which is often associated with the malfunction of both T cells and B cells with T cells playing a more major role. A number of therapeutic mediators for autoimmune diseases are available, from conventional disease-modifying drugs to biologic agents and small molecule inhibitors. Recently, ribosomally synthesized peptides, specifically cyclotides from plants are currently attracting more attention as potential autoimmune disease therapeutics due to their decreased toxicity compared to small molecules inhibitors as well as their remarkable stability against a number of factors. This review provides a concise overview of various cyclotides exhibiting immunomodulatory properties and their potential as therapeutic interventions for autoimmune diseases.

Low-Carbohydrate Diet Score and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study.

Limited data are reported on the association between low-carbohydrate diet (LCD) score, a comprehensive measure of dietary pattern according to sources of carbohydrate, fat, and protein, and risk of hepatocellular carcinoma (HCC). We evaluated this score with HCC risk in the Singapore Chinese Health Study, a prospective cohort of 63,275 middle-aged and elderly Chinese living in Singapore and recruited during 1993-1998 period. LCD scores were derived from the semi-quantitative food frequency questionnaire at baseline. A nested case-control study involved 197 HCC cases and 465 controls was also constructed among 28,346 participants who provided blood samples. Cox proportional hazard regression method was used to calculate HRs and 95% confidence intervals (CI) for HCC with different levels of LCD scores. Conditional logistic regression was performed for the case-control study analysis. After 17.6 years of follow-up with 819,573 person-years, 561 participants developed primary HCC. Although there was a null association between total LCD score and HCC risk (HRper-SD increment = 1.07; 95% CI, 0.98-1.16; Ptrend = 0.06), there was a positive association between animal-based LCD and the risk of HCC (HRper-SD increment = 1.11; 95% CI, 1.02-1.21; Ptrend = 0.01). Furthermore, this association was present in both HBsAg-negative and HBsAg-positive individuals in the case-control study. In stratified analysis for the entire cohort, this positive association was only present in those who consumed alcoholic beverages monthly or less frequent but not in weekly or daily drinker (Pinteraction = 0.79). In summary, a diet with lower carbohydrate, higher animal fat and protein was significantly associated with higher risk of HCC among Chinese Singaporeans. PREVENTION RELEVANCE: In a large cohort study of more than 63,000 Chinese Singaporeans, we found that a diet with lower carbohydrate and higher animal fat and protein was associated with increased risk of HCC, suggesting that dietary modification could be an effective strategy in primary prevention to reduce the HCC burden.

Depression and associated factors among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam: a cross-sectional analysis.

OBJECTIVES: To assess the prevalence of depressive symptoms and associated factors among people living with HIV (PLWH) who were current cigarette smokers and receiving treatment at HIV outpatient clinics (OPCs) in Vietnam. DESIGN: A cross-sectional survey of smokers living with HIV. SETTING: The study was carried out in 13 HIV OPCs located in Ha Noi, Vietnam. PARTICIPANTS: The study included 527 PLWH aged 18 and above who were smokers and were receiving treatment at HIV OPCs. OUTCOME MEASURES: The study used the Centre for Epidemiology Scale for Depression to assess depressive symptoms. The associations between depressive symptoms, tobacco dependence and other characteristics were explored using bivariate and Poisson regression analyses. RESULTS: The prevalence of depressive symptoms among smokers living with HIV was 38.3%. HIV-positive smokers who were female (prevalence ratio, PR 1.51, 95% CI 1.02 to 2.22), unmarried (PR 2.06, 95% CI 1.54 to 2.76), had a higher level of tobacco dependence (PR 1.06, 95% CI 1.01 to 1.11) and reported their health as fair or poor (PR 1.66, 95% CI 1.22 to 2.26) were more likely to have depression symptoms compared with HIV-positive smokers who were male, married, had a lower level of tobacco dependence and self-reported their health as good, very good or excellent. CONCLUSION: The prevalence of depressive symptoms among smokers receiving HIV care at HIV OPCs was high. Both depression and tobacco use screening and treatment should be included as part of ongoing care treatment plans at HIV OPCs.

Tryptophan intake and pancreatic cancer: findings from a case-control study.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam. METHODS: We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk. RESULTS: Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) ( Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m 2 and ever drinkers. CONCLUSION: A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

Social support among English learners with disabilities and other adolescents.

INTRODUCTION: Social support is important for many youth but may be particularly important for English learners (ELs) with disabilities, a population that has historically faced barriers accessing resources to meet their educational needs. The current study investigates social support from parents, peers, teachers, and schools in a nationally representative sample of adolescents. METHOD: Data from the National Longitudinal Transition Study 2012 was used to evaluate potential group differences in social support among participants that included ELs with (n = 440) and without disabilities (n = 100) and non-ELs with (n = 4890) and without disabilities (n = 1090). A multivariate analysis of covariance was conducted to evaluate potential between-group variations in social support among these student groups after controlling for variations in background demographic characteristics. RESULTS AND CONCLUSIONS: Results showed between group differences in parental support and peer connectedness but not in teacher or school support. Parents of students with disabilities reported the highest levels of support, whereas parents of ELs without disabilities reported the lowest levels of support. Students with disabilities reported the lowest levels of peer connectedness among the four groups. Overall, levels of teacher and school supports were high across all four groups of students. These patterns contribute to our understanding of the social support network of ELs with disabilities in comparison to other students. Further investigation is needed to examine the mechanisms that contribute to these differences.

Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction.

BACKGROUND: Early-onset fetal growth restriction (FGR) is associated with adverse outcomes. We hypothesised that maternal melatonin administration will improve fetal brain structure in FGR. METHODS: Surgery was performed on twin-bearing ewes at 88 days (0.6 gestation), and FGR induced in one twin via single umbilical artery ligation. Melatonin was administered intravenously (6 mg/day) to a group of ewes commencing on day of surgery until 127 days (0.85 gestation), when the ewe/fetuses were euthanized, and fetal brains collected. RESULTS: Study groups were control (n = 5), FGR (n = 5), control+melatonin (control+MLT; n = 6) and FGR+melatonin (FGR + MLT; n = 6). Melatonin administration did not significantly alter fetal body or brain weights. Myelin (CNPase+) fibre density was reduced in FGR vs. control animals in most brain regions examined (p < 0.05) and melatonin treatment restored CNPase fibre density. Similar but less pronounced effect was seen with mature myelin (MBP+) staining. Significant differences in activated microglia (Iba-1) activity were seen between lamb groups (MLT mitigated FGR effect) in periventricular white matter, subventricular zone and external capsule (p < 0.05). Similar effects were seen in astrogliosis (GFAP) in intragyral white matter and cortex. CONCLUSIONS: Maternal melatonin administration in early onset FGR led to improved myelination of white matter brain regions, possibly mediated by decreased inflammation. IMPACT: Maternal melatonin administration might lead to neuroprotection in the growth-restricted fetus, possibly via dampening neuroinflammation and enhancing myelination. This preclinical study adds to the body of work on this topic, and informs clinical translation. Neuroprotection likely to improve long-term outcomes of this vulnerable infant group.

Transition Metal Dichalcogenides: Making Atomic-Level Magnetism Tunable with Light at Room Temperature.

The capacity to manipulate magnetization in 2D dilute magnetic semiconductors (2D-DMSs) using light, specifically in magnetically doped transition metal dichalcogenide (TMD) monolayers (M-doped TX2 , where M = V, Fe, and Cr; T = W, Mo; X = S, Se, and Te), may lead to innovative applications in spintronics, spin-caloritronics, valleytronics, and quantum computation. This Perspective paper explores the mediation of magnetization by light under ambient conditions in 2D-TMD DMSs and heterostructures. By combining magneto-LC resonance (MLCR) experiments with density functional theory (DFT) calculations, we show that the magnetization can be enhanced using light in V-doped TMD monolayers (e.g., V-WS2 , V-WSe2 ). This phenomenon is attributed to excess holes in the conduction and valence bands, and carriers trapped in magnetic doping states, mediating the magnetization of the semiconducting layer. In 2D-TMD heterostructures (VSe2 /WS2 , VSe2 /MoS2 ), the significance of proximity, charge-transfer, and confinement effects in amplifying light-mediated magnetism is demonstrated. We attributed this to photon absorption at the TMD layer that generates electron-hole pairs mediating the magnetization of the heterostructure. These findings will encourage further research in the field of 2D magnetism and establish a novel design of 2D-TMDs and heterostructures with optically tunable magnetic functionalities, paving the way for next-generation magneto-optic nanodevices.

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.

Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic-Ischaemic Brain Injury in Rats.

(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic-ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (p < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (p < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.

Cardiovascular decline in offspring during the perinatal period in an ovine model of fetal growth restriction.

Fetal growth restriction (FGR) increases the risk cardiovascular disease (CVD) in adulthood. Placental insufficiency and subsequent chronic fetal hypoxemia are causal factors for FGR, leading to a redistribution of blood flow that prioritizes vital organs. Subclinical signs of cardiovascular dysfunction are evident in growth-restricted neonates; however, the mechanisms programming for CVD in adulthood remain unknown. This study aimed to determine the potential mechanisms underlying structural and functional changes within the heart and essential (carotid) and nonessential (femoral) vascular beds in growth-restricted lambs. Placental insufficiency was surgically induced in ewes at 89 days gestational age (dGA, term = 148dGA). Three age groups were investigated: fetal (126dGA), newborn (24 h after preterm birth), and 4-wk-old lambs. In vivo and histological assessments of cardiovascular indices were undertaken. Resistance femoral artery function was assessed via in vitro wire myography and blockade of key vasoactive pathways including nitric oxide, prostanoids, and endothelium-dependent hyperpolarization. All lambs were normotensive throughout the first 4 wk of life. Overall, the FGR cohort had more globular hearts compared with controls (P = 0.0374). A progressive decline in endothelium-dependent vasodilation was demonstrated in FGR lambs compared with controls. Further investigation revealed that impairment of the prostanoid pathway may drive this reduction in vasodilatory capacity. Clinical indicators of CVD were not observed in our FGR lambs. However, subclinical signs of cardiovascular dysfunction were present in our FGR offspring. This study provides insight into potential mechanisms, such as the prostanoid pathway, that may warrant therapeutic interventions to improve cardiovascular development in growth-restricted newborns.NEW & NOTEWORTHY Our findings provide novel insight into the potential mechanisms that program for cardiovascular dysfunction in growth-restricted neonates as our growth-restricted lambs exhibited a progressive decline in endothelium-dependent vasodilation in the femoral artery between birth and 4 wk of age. Subsequent analyses indicated that this reduction in vasodilatory capacity is likely to be mediated by the prostanoid pathway and prostanoids could be a potential target for therapeutic interventions for fetal growth restriction (FGR).