Early Course Research Articles

The association between weight during early life and multiple sclerosis onset in a nationwide Dutch birth year cohort

ABSTRACT Background The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS case status, age of first symptom onset and onset type in people with MS (pwMS) of the same birth year. Methods We enrolled 363 PwMS and 125 healthy controls (HC) from Project Y, a Dutch population-based cross-sectional cohort study including all PwMS born in 1966 and age and sex-matched HC. The associations between weight during childhood and adolescence (non-overweight vs. overweight or obese) and MS, age at symptom onset and onset type (relapsing vs. progressive) were assessed using logistic and linear regressions. In addition, sex-separated associations were explored. Results Being overweight or obese during childhood (OR = 2.82, 95% CI 1.17–6.80) and adolescence (OR = 2.45, 95% CI 1.13–5.34) was associated with developing MS. Furthermore, being overweight or obese during adolescence was associated with a younger age of onset (β = −0.11, p = 0.041). Of all 47 patients with a primary progressive (PP) onset type, only one patient (2.1%) was overweight or obese during childhood, whereas 45 patients with a relapsing remitting (RR) onset (14.3%) were overweight or obese during childhood (PP vs. RR p = 0.017; PP vs. HC p = 0.676; RR vs. HC, p = 0.015). However, using logistic regression analysis we did not find evidence of a significant association. Conclusion In a nationwide population-based birth year cohort, being overweight or obese during childhood or adolescence is associated with MS prevalence and an earlier age of onset, but does not seem to associate with the type of onset.

Epidemic Cholera and Reform in the 19th Century

We tend to think of Big History in a ‘big way’ – the cosmos, billions of years, trillions of kilometres … but this isn’t the whole picture. Biologist Lynn Margulis produced a book about small-scale life, Microcosmos (1986), which led her to collaborate with chemist James Lovelock on Earth dynamics. In this way, molecular biologist Elizabeth Martin-Kutter also worked with microbial life and helped develop one of early courses and texts in Cosmic Evolution and Big History with astrophysicist G. Siegfried Kutter.

A study protocol for community implementation of a new mental health monitoring system spanning early childhood to young adulthood

Findings from longitudinal research, globally, repeatedly emphasise the importance of taking an early life course approach to mental health promotion; one that invests in the formative years of development, from early childhood to young adulthood, just prior to the transition to parenthood for most. While population monitoring systems have been developed for this period, they are typically designed for use within discrete stages (i.e., childhood or adolescent or young adulthood). No system has yet captured development across all ages and stages (i.e., from infancy through to young adulthood). Here we describe the development, and pilot implementation, of a new Australian Comprehensive Monitoring System (CMS) designed to address this gap by measuring social and emotional development (strengths and difficulties) across eight census surveys, separated by three yearly intervals (infancy, 3-, 6-, 9- 12-, 15-, 18 and 21 years). The system also measures the family, school, peer, digital and community social climates in which children and young people live and grow. Data collection is community-led and built into existing, government funded, universal services (Maternal Child Health, Schools and Local Learning and Employment Networks) to maximise response rates and ensure sustainability. The first system test will be completed and evaluated in rural Victoria, Australia, in 2022. CMS will then be adapted for larger, more socio-economically diverse regional and metropolitan communities, including Australian First Nations communities. The aim of CMS is to guide community-led investments in mental health promotion from early childhood to young adulthood, setting secure foundations for the next generation.

The role of triglyceride-glucose index in predicting cardiovascular and metabolic outcomes in patients with type 2 diabetes mellitus

Diabetes mellitus type 2 is a global medical and social problem, which, in terms of population coverage around the world, is becoming a pandemic. The main cause of premature death in patients with type 2 diabetes is diseases of the cardiovascular system. The presence of diabetes is associated with an increase in the risk of developing coronary heart disease by two-four times, and every sixth patient has signs of myocardial infarction in the past. The risk of developing ASCVD in patients with type 2 diabetes is early onset, rapid progression, and asymptomatic course. It is known that patients with type 2 diabetes develop ASCVD 8–10 years earlier than people of the same age group who do not have diabetes. Along with chronic hyperglycemia, an independent risk factor for cardiovascular complications in patients with type 2 diabetes is dyslipidemia, which occurs in 30–40% of patients. Insulin resistance, the state of chronic hyperglycemia, dyslipidemia play a key role in the development of the metabolic syndrome and atherosclerosis. The TyG index and the parameter of non-HDL-C have convincingly established themselves as predictors of the development of CVD, as well as markers reflecting signs of the presence of independent factors of the metabolic syndrome that increase the risk of CVD. Conducted clinical studies have confirmed the predictive value of these parameters in relation to CVD. This review focuses on the pathogenesis, development mechanisms, and methods for correcting lipid disorders that underlie the development of CV complications in patients with type 2 diabetes.

1566-P: The TM6SF2 rs58542926 Polymorphism Dissociates Hepatocellular Lipids from Insulin Resistance in Recent-Onset Type 2 Diabetes

Increased hepatocellular lipid content (HCL) is generally linked to insulin resistance, which contributes to greater risk of type 2 diabetes and cardiovascular complications. Conversely, a single-nucleotide polymorphism (TM6SF2EK; rs58542926) in the transmembrane 6 superfamily member 2 gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. Thus, this case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during the early course of diabetes. Males with recent-onset type 2 diabetes with (TM6SF2EK: n=16) or without (TM6SF2EE: n=16) the heterozygous TM6SF2 polymorphism of similar age and BMI, underwent Botnia-clamps with [6,6-2H2]glucose to measure whole-body, hepatic and adipose tissue insulin sensitivity. HCL and liver fibrosis were assessed with 1H-magnetic resonance spectroscopy and non-invasive tests (FIB4, APRI, AST/ALT), respectively. A subset of both groups (n=24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2EK had similar hepatic and adipose tissue insulin sensitivity and even 27% higher whole-body insulin sensitivity than TM6SF2EE. The novel diabetes endotypes were equally distributed among both groups. After 5 years, whole-body insulin sensitivity, HCL and liver fibrosis indices were similar, while adipose tissue insulin sensitivity decreased by 87% and 55% both in TM6SF2EK and TM6SF2EE and circulating triacylglycerol increased in TM6SF2EE only. The TM6SF2 gene polymorphism rs58542926 dissociates ectopic fat content from insulin resistance in recent-onset type 2 diabetes, which is however attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over the effects of the TM6SF2 gene polymorphism during the early course of diabetes and NAFLD. Disclosure K.Bódis: None. R.Guthoff: Other Relationship; Alimera, Bayer Inc., Novartis, Allergan. V.Schrauwen-hinderling: None. H.Al-hasani: None. V.Burkart: None. J.Szendroedi: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. D.F.Markgraf: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. M.Bombrich: None. M.Schön: None. B.Knebel: None. O.P.Zaharia: None. G.J.Bönhof: None. Y.Karusheva: None. Y.Kupriyanova: None. J.Kotzka: None.

Takotsubo cardiomyopathy associated with Herpes simplex encephalitis: A case report and literature review

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy characterized by transient left ventricular dysfunction. It can be triggered by various central nervous system pathologies including status epilepticus (SE) and N-methyl-d-aspartate receptor (NMDAr) encephalitis. Herpex simplex encephalitis (HSE) is a life-threatening, sporadic, encephalitis associated with focal or global cerebral dysfunction caused by herpes simplex viruses type 1(HSV-1), or less commonly, type 2(HSV-2). While approximately 20% of patients with HSE develop NMDAr antibodies, not all manifest with encephalitis clinically. We present here a 77-year-old woman admitted with HSV-1 encephalitis who presented with acute encephalopathy and seizure-like activity. Continuous EEG monitoring (cEEG) showed periodic lateralized epileptiform discharges (PLEDs) involving the left parietotemporal region but no evidence of electrographic seizures. Her early hospital course was complicated by TCM which subsequently resolved on repeat TTE. She demonstrated initial neurological improvement. However, five weeks later her mental status declined. Again, no seizures were appreciated on cEEG. Unfortunately, repeat studies including lumbar puncture and magnetic resonance imaging (MRI) of the brain were consistent with NMDAr encephalitis. She was treated with immunosuppression and immunomodulation therapies. To our knowledge we report the first case of TCM secondary to HSE without comorbid status epilepticus. However, further studies are needed to better understand the correlation between, and underlying pathophysiology of HSE and TCM, as well as any potential association with this presentation and subsequent development of NMDAr encephalitis.

Consistency of left ventricular ejection fraction measurements in the early time course of STEMI.

Early after ST-segment elevation myocardial infarction (STEMI), initial LV reshaping and hypokinesia may affect analysis of LV function. Concomitant microvascular dysfunction may affect LV function as well. To perform a comparative evaluation of left ventricular ejection fraction (LVEF) and stroke volume (SV) by different imaging modalities to assess LV function early after STEMI. LVEF and SV were assessed using serial imaging within 24 h and 5 days after STEMI using cineventriculography (CVG), 2-dimensional echocardiography (2DE), 2D/3D cardiovascular magnetic resonance (CMR) (2D/3D) in 82 patients. 2D analyses of LVEF using CVG, 2DE and 2D CMR yielded uniform results within 24 h and 5 days of STEMI. SV assessment between CVG and 2DE was comparable, whereas values for SV were higher using 2D CMR (p < 0.01 all). This was due to higher LVEDV measurements. LVEF by 2D versus 3D CMR was comparable, 3D CMR yielded higher volumetric values. This was not influenced by infarct location or infarct size. 2D analysis of LVEF yielded robust results across all imaging techniques implying that CVG, 2DE, and 2D CMR can be used interchangeably early after STEMI. SV measurements differed substantially between imaging techniques due to higher intermodality-differences of absolute volumetric measurements.

Gene expression of S100a8/a9 predicts Staphylococcus aureus-induced septic arthritis in mice.

Septic arthritis is the most aggressive joint disease associated with high morbidity and mortality. The interplay of the host immune system with the invading pathogens impacts the pathophysiology of septic arthritis. Early antibiotic treatment is crucial for a better prognosis to save the patients from severe bone damage and later joint dysfunction. To date, there are no specific predictive biomarkers for septic arthritis. Transcriptome sequencing analysis identified S100a8/a9 genes to be highly expressed in septic arthritis compared to non-septic arthritis at the early course of infection in an Staphylococcus aureus septic arthritis mouse model. Importantly, downregulation of S100a8/a9 mRNA expression at the early course of infection was noticed in mice infected with the S. aureus Sortase A/B mutant strain totally lacking arthritogenic capacity compared with the mice infected with parental S. aureus arthritogenic strain. The mice infected intra-articularly with the S. aureus arthritogenic strain significantly increased S100a8/a9 protein expression levels in joints over time. Intriguingly, the synthetic bacterial lipopeptide Pam2CSK4 was more potent than Pam3CSK4 in inducing S100a8/a9 release upon intra-articular injection of these lipopeptides into the mouse knee joints. Such an effect was dependent on the presence of monocytes/macrophages. In conclusion, S100a8/a9 gene expression may serve as a potential biomarker to predict septic arthritis, enabling the development of more effective treatment strategies.

The impact of postoperative complications on oncological outcomes of liver transplantation for hepatocellular carcinoma: A competing risk analysis

ObjectiveTo investigate the influence of postoperative complications on tumor-related (TRD), disease-free survival (DFS) and overall survival (OS) in patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC). MethodsWe retrospectively evaluated 425 LTs for HCC from 2010 to 2019. Postoperative complications were classified according to Comprehensive Complication Index (CCI) and the posttransplant risk of TRD assessed through Metroticket 2.0 calculator. The population was stratified into high-risk and low-risk cohorts based on the predicted TRD risk of 80%. In a second step, we re-evaluated TRD, DFS and OS of both cohorts according to a further stratification based on 47.3 points of CCI cut-off. ResultsIn the low-risk cohort, we observed a significantly better DFS (84% vs. 46%, p<0.001), TRD (3% vs. 26%, p<0.001) and OS (89% vs. 62%, p<0.001) in the group with CCI < 47.3. In the high-risk cohort, patients with CCI < 47.3 had significantly better DFS (50% vs. 23%, p = 0.003) and OS (68% vs. 42%, p = 0.02) and a comparable TRD (22% vs. 31%, p = 0.142). ConclusionsA complicated postoperative course negatively influenced long-term survival. This poorer oncological outcome associated with in-hospital postoperative complications suggests that every effort should be made to improve the early posttransplant course in HCC patients, including a careful donor-to recipient match and use of new perfusion technologies.

Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes

Background and aimsIncreased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes. Methods and resultsMales with recent-onset type 2 diabetes with (TM6SF2EK: n = 16) or without (TM6SF2EE: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-2H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with 1H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2EE. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2EE only. ConclusionsThe TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.

Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

Certain antibiotic exposures have been associated with increased rates of acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Since antibiotic exposure can both affect and be affected by infections, analyzing time-dependent exposure in the presence of multiple potential confounders, including prior antibiotic exposures, poses specific analytical challenges, necessitating both a large sample size and unique approaches. To identify antibiotics and antibiotic exposure timeframes associated with subsequent aGVHD. This cohort study assessed allo-HCT at a single center from 2010 to 2021. Participants included all patients aged at least 18 years who underwent their first T-replete allo-HCT, with at least 6 months of follow-up. Data were analyzed from August 1 to December 15, 2022. Antibiotics between 7 days before and 30 days after transplant. The primary outcome was grade II to IV aGVHD. The secondary outcome was grade III to IV aGVHD. Data were analyzed using 3 orthogonal methods: conventional Cox proportional hazard regression, marginal structural models, and machine learning. A total of 2023 patients (median [range] age, 55 [18-78] years; 1153 [57%] male) were eligible. Weeks 1 and 2 after HCT were the highest-risk intervals, with multiple antibiotic exposures associated with higher rates of subsequent aGVHD. In particular, exposure to carbapenems during weeks 1 and 2 after allo-HCT was consistently associated with increased risk of aGVHD (minimum hazard ratio [HR] among models, 2.75; 95% CI, 1.77-4.28), as was week 1 after allo-HCT exposure to combinations of penicillins with a β-lactamase inhibitor (minimum HR among models, 6.55; 95% CI, 2.35-18.20). In this cohort study of allo-HCT recipients, antibiotic choices and schedules in the early course of transplantation were associated with aGVHD rates. These findings should be considered in antibiotic stewardship programs.

Time to play, time to think: meaningful moments in the forest

ABSTRACT This paper reports on a study carried out by tutors and students on Early Childhood Studies degree courses at a University in England. The research explored perspectives of three to six-year-old children’s outdoor play in Danish forest kindergartens with the aim of troubling and informing approaches to outdoor pedagogy. Inspired by Somerville and Powell’s ‘deep hanging out’ ([Somerville, M., and J. Powell. 2018. “Thinking Posthuman with Mud: And Children of the Anthropocene.” Educational Philosophy and Theory 51 (8): 829–840. https://doi.org/10.1080/00131857.2018.1516138, 1) with data, researchers visited the kindergartens for a full day at a time during annual week-long field visits. This provided opportunities to notice the children’s journeys and possibilities over time. Findings showed that, given time and space to play in the forest, children were able to pursue their interests, engage in extended periods of concentration and thinking while working together as they played and explored with each other, with the educators and with the materiality of their surroundings. Implications for practitioners highlight the need to provide uninterrupted time for children to develop their curiosities and enjoyment of the outdoor environment.

Dynamics of pulmonary hypertension severity in the first 48 h in neonates with prenatally diagnosed congenital diaphragmatic hernia.

Pulmonary hypertension (PH) is one of the major contributing factors to the high morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). The severity and duration of postnatal PH are an established risk factor for patient outcome; however, the early postnatal dynamics of PH have not been investigated. This study aims to describe the early course of PH in CDH infants, and its relation to established prognostic markers and outcome measures. We performed a monocentric retrospective review of neonates with prenatally diagnosed CDH, who received three standardized echocardiographic examinations at 2-6 h, 24, and 48 h of life. The degree of PH was graded as one of three categories: mild/no, moderate, or severe PH. The characteristics of the three groups and their course of PH over 48 h were compared using univariate and correlational analyses. Of 165 eligible CDH cases, initial PH classification was mild/no in 28%, moderate in 35%, and severe PH in 37%. The course of PH varied markedly based on the initial staging. No patient with initial no/mild PH developed severe PH, required extracorporeal membrane oxygenation (ECMO)-therapy, or died. Of cases with initial severe PH, 63% had persistent PH at 48 h, 69% required ECMO, and 54% died. Risk factors for any PH included younger gestational age, intrathoracic liver herniation, prenatal fetoscopic endoluminal tracheal occlusion (FETO)-intervention, lower lung to head ratio (LHR), and total fetal lung volume (TFLV). Patients with moderate and severe PH showed similar characteristics, except liver position at 24- (p = 0.042) and 48 h (p = 0.001), mortality (p = 0.001), and ECMO-rate (p = 0.035). To our knowledge, this is the first study to systematically assess the dynamics of PH in the first postnatal 48 h at three defined time points. CDH infants with initial moderate and severe PH have a high variation in postnatal PH severity over the first 48 h of life. Patients with mild/no PH have less change in PH severity, and an excellent prognosis. Patients with severe PH at any point have a significantly higher risk for ECMO and mortality. Assessing PH within 2-6 h should be a primary goal in the care for CDH neonates.

FLOT plus nivolumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Results from the randomized phase 2 IKF-S628/AIO-STO-0417 (Moonlight) trial of the AIO.

4045 Background: FOLFOX plus nivolumab (nivo) has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas. FLOT is a well-established standard of care triplet regime. Some physicians may consider a triplet in patients with aggressive disease. The aim of this Arm C part of the Moonlight trial was to evaluate the safety and efficacy of the combination of FLOT plus nivo. Methods: Moonlight is a multi-cohort phase-II trial. The results for Arm C evaluating FLOT + nivo (240 mg) q2w as first-line therapy in all-comers are presented here. Primary endpoint was progression-free survival at 6 months (PFS@6), main secondary endpoints were safety, OS, and overall response rate (ORR). Results: Fifty-two patients were enrolled. Baseline characteristics were: median age 61y, GEJ 65%. Sixty-five percent had centrally assessed PD-L1 CPS≥1 (available in 96% of pts). Pts. received a median number of 8 cycles of FLOT and nivo and 42% received further line treatment. FLOT plus nivo was well tolerated and feasible with the most frequent adverse events of ≥ grade 3 being decreased neutrophils (40.4%), anemia (5.8%) and thromboembolic events (7.7%). After a median follow-up of 9.4 months, 3- and 6-month progression-free survival rates were 85% and 42%, respectively. Median PFS was 6.6 months and median OS 10.8 months. ORR and disease control rate (DCR) were 54% and 87%, respectively. Compared to the pooled study cohorts A and A1 (n = 90 pts) utilizing mFOLFOX plus nivo and ipilimumab (non-randomized comparison), FLOT plus nivo was associated with greater DCR (87% vs. 78%) and 3-months PFS (85% vs. 72%). Conclusions: FLOT and nivo is feasible and seems to be associated with improved disease control in the early course of therapy. FLOT plus nivo may represent an option for select patients with aggressive, rapidly progressive disease. Clinical trial information: NCT03647969 .

Innovations in social health delivery to advance equitable pediatric and adolescent life course health development: A review and roadmap forward

Recognizing the influence of social determinants on health and development, health care has increasingly advocated for interventions that target upstream factors as part of routine pediatric care delivery. In response, clinic-based social risk screening and referral programs have proliferated wherein patients are screened for health-related social needs (HRSNs, such as food and housing insecurity) and referred to community-based organizations (CBOs) and social service providers to address those needs. In recent years, an array of digital platforms, known as Social Health Access and Referral Platforms (SHARPs), have emerged to facilitate the scale and implementation of these models amidst growing system demand.Recent evidence on the effectiveness of social risk screen and refer models and SHARPs has been mixed, giving researchers pause and calling for more nuanced understanding of the limitations of such models, especially for promoting child and family health. Design thinking informed by the Life-Course Health Development (LCHD) framework provides a particularly useful lens for synthesizing emerging limitations of such models in the pediatric context, given the dynamic and developmentally-driven circumstances that shape family health and well-being in the early life course. By (1) focusing on addressing deficits-based social risks, (2) scoping to act upon narrow, downstream needs, (3) timing to react to social needs that have already caused harm rather than preventing them, and (4) limiting scale to individual-by-individual responses rather than structural and population-wide interventions, the current design of prevailing social risk screen and refer programs fundamentally limits their potential impact and misses opportunities to improve health equity over the life course.How can health care, social care, and technology partners move forward in collaboration with families and communities to better support equitable lifelong health and social development? In this narrative review, we will summarize the current design, implementation, and limitations of the predominant social risk screen and refer approach in the context of early childhood and adolescent care delivery. We then will apply LCHD principles to advance and improve on this approach from a reactionary focus towards a Family Journey Model that better supports life course health development.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Teaching to (un)learn: enacting social justice in the identity development of multilingual/Latinx/BIPOC teacher candidates

PurposeThis paper aims to describe how engaging in an inquiry-as-stance reflexive approach informed the design of a graduate-level early childhood social studies methods course to support the professional identity development of multilingual/Latinx, Black, Indigenous, people of color (ML/L/BIPOC) teacher candidates.Design/methodology/approachNested within a theoretical construct that articulates “unlearning as a disruptive force” (Dunne, 2016), the author used a parallel process that modeled the teaching of social studies methods grounded in critical reflections of students’ cultural and linguistic assets. In so doing, the author shares how she models culturally and linguistically responsive-sustaining pedagogy in practice.FindingsThe findings illustrate that in this course, students begin unlearning internalized deficit narratives that they have been socialized to believe about themselves and, often, their students.Research limitations/implicationsThis study is based on only four semesters of teaching one graduate-level methods course to ML/L/BIPOC early childhood educators at one institution, research results may lack generalizability. Therefore, researchers are encouraged to test the proposed propositions further.Originality/valueThrough unlearning, ML/L/BIPOC learn to recognize their assets, dispositions, skills and capacities more fully and, thus, are more able to enact culturally responsive-sustaining pedagogy once in their own classrooms. As such, this study has value for applying critical, identity-centered and asset-based pedagogies in teacher preparation programs.

Effects of Dl-3-n-butylphthalide on cognitive functions and blood–brain barrier in chronic cerebral hypoperfusion rats

Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood–brain barrier damage plays an essential part in the pathogenesis of VCI. At present, the treatment of VCI is mainly focused on prevention, with no drug clinically approved for the treatment of VCI. This study aimed to investigate the effects of DL-3-n-butylphthalide (NBP) on VCI rats. A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to mimic VCI. The feasibility of the mBCCAO model was verified by laser Doppler, 13N-Ammonia-Positron Emission Computed Tomography (PET), and Morris Water Maze. Subsequently, the Morris water maze experiment, Evans blue staining, and western blot of tight junction protein were performed to evaluate the effect of different doses of NBP (40 mg/kg, 80 mg/kg) on the improvement of cognitive impairment and BBB disruption induced by mBCCAO. Immunofluorescence was employed to examine the changes in pericyte coverage in the mBCCAO model and the effect of NBP on pericyte coverage was preliminarily explored. mBCCAO surgery led to obvious cognitive impairment and the decrease of whole cerebral blood flow, among which the blood flow in the cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviated Evans blue leakage and reduced the loss of tight junction proteins (ZO-1, Claudin-5) in the early course of the disease, thereby exerting a protective effect on the blood–brain barrier. No significant changes in pericyte coverage were observed after mBCCAO. High-dose NBP improved cognitive function in mBCCAO rats. High-dose NBP protected the integrity of BBB by upregulating TJ protein expression, rather than regulating pericyte coverage ratio. NBP could be a potential drug for the treatment of VCI.

Dynamic Stability of Volatile Organic Compounds in Respiratory Air in Schizophrenic Patients and Its Potential Predicting Efficacy of TAAR Agonists.

Volatile organic compounds (VOCs) in the breathing air were found to be altered in schizophrenia patients compared to healthy participants. The aim of this study was to confirm these findings and to examine for the first time whether these VOCs are stable or change in concentration during the early treatment course. Moreover, it was investigated whether there is a correlation of the VOCs with the existing psychopathology of schizophrenia patients, i.e., whether the concentration of masses detected in the breath gas changes when the psychopathology of the participants changes. The breath of a total of 22 patients with schizophrenia disorder was examined regarding the concentration of VOCs using proton transfer reaction mass spectrometry. The measurements were carried out at baseline and after two weeks at three different time points, the first time immediately after waking up in the morning, after 30 min, and then after 60 min. Furthermore, 22 healthy participants were investigated once as a control group. Using bootstrap mixed model analyses, significant concentration differences were found between schizophrenia patients and healthy control participants (m/z 19, 33, 42, 59, 60, 69, 74, 89, and 93). Moreover, concentration differences were detected between the sexes for masses m/z 42, 45, 57, 69, and 91. Mass m/z 67 and 95 showed significant temporal changes with decreasing concentration during awakening. Significant temporal change over two weeks of treatment could not be detected for any mass. Masses m/z 61, 71, 73, and 79 showed a significant relationship to the respective olanzapine equivalents. The length of hospital stay showed no significant relationship to the masses studied. Breath gas analysis is an easy-to-use method to detect differences in VOCs in the breath of schizophrenia patients with high temporal stability. m/z 60 corresponding to trimethylamine might be of potential interest because of its natural affinity to TAAR receptors, currently a novel therapeutic target under investigation. Overall, breath signatures seemed to stable over time in patients with schizophrenia. In the future, the development of a biomarker could potentially have an impact on the early detection of the disease, treatment, and, thus, patient outcome.

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.

NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.