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Paediatric Respiratory Reviews Jun 2024Obstructive sleep apnea (OSA) due to a hypertrophy of the adenoids and/or the tonsils in otherwise healthy children is associated with neurocognitive dysfunction and... (Review)
Review
Obstructive sleep apnea (OSA) due to a hypertrophy of the adenoids and/or the tonsils in otherwise healthy children is associated with neurocognitive dysfunction and behavioural disorders with various degrees of hyperactivity, aggressiveness, sometimes evolving to a label of attention-deficit hyperactivity disorder. Children with anatomical and/or functional abnormalities of the upper airways represent a very specific population which is at high risk of OSA (also called complex OSA or OSA type III). Surprisingly, the neurocognitive consequences of OSA have been poorly studied in these children, despite the fact that OSA is more common and more severe than in their healthy counterparts. This may be explained by that fact that screening for OSA and sleep-disordered breathing is not systematically performed, the performance of sleep studies and neurocognitive tests may be challenging, and the respective role of the underlining disease, OSA, but also poor sleep quality, is complex. However, the few studies that have been performed in these children, and mainly children with Down syndrome, tend to show that OSA, but even more disruption of sleep architecture and poor sleep quality, aggravate the neurocognitive impairment and abnormal behaviour in these patients, underlining the need for a systematic and early in life assessment of sleep and neurocognitive function and behaviour in children with OSA type III.
PubMed: 38908984
DOI: 10.1016/j.prrv.2024.06.004 -
Journal of Reproductive Immunology Jun 2024Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin,...
Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, -3 and -9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1 pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface.
PubMed: 38908337
DOI: 10.1016/j.jri.2024.104284 -
Research in Developmental Disabilities Jun 2024Narrative ability is crucial for social participation in everyday and school life but involves different language abilities such as vocabulary and morpho-syntax. This is...
BACKGROUND
Narrative ability is crucial for social participation in everyday and school life but involves different language abilities such as vocabulary and morpho-syntax. This is particularly difficult for individuals who display both language and cognitive impairments. Previous research has identified productive vocabulary as a possible key factor for narrative performance in individuals with Down syndrome. Considering a close connection between lexical and morpho-syntactic performance within language acquisition and the distinct impairments that individuals with Down syndrome display concerning their morpho-syntactic skills, the nature of a relation between vocabulary and narrative skills under the influence of grammatical deficits requires further investigation.
METHODS
Narrations were obtained from 28 children and adolescents with Down syndrome (aged 10;0-20;1) using a non-verbal picture book. Narrative abilities were rated using the Narrative Scoring Scheme across seven narrative aspects (including macro- and microstructure). Vocabulary analyses and morpho-lexical context analyses including verb and conjunction enumerations, evaluation of verb position and MLU were conducted. Findings from the transcript analysis have been supplemented with data from standardized language measures evaluating expressive lexical and morpho-syntactic development. A multiple regression analysis was conducted to identify significant predictors for narrative outcome in the participants with Down syndrome.
RESULTS
Lexical analyses revealed a high heterogeneity in production of subordinating conjunctions as a link between lexical and morpho-syntactic abilities. Comparisons of standardized and narrative data demonstrated differences in subordinate clause production depending on the elicitation setting. A multiple regression analysis identified the number of different verbs in the narrative task as the most significant predictor for narrative performance in individuals with Down syndrome.
DISCUSSION AND IMPLICATIONS
The findings of this study contribute to the knowledge regarding factors that influence narrative performance in individuals with language impairment. A differentiated verb lexicon can be identified as the key ability for reaching advanced narrative skills in participants with Down syndrome. These findings are of clinical relevance for therapeutic and educational support and contribute to an understanding of the relation between strengths in vocabulary and morpho-syntactic weaknesses in individuals with Down syndrome within communicative participation.
PubMed: 38908111
DOI: 10.1016/j.ridd.2024.104781 -
Clinical Oral Investigations Jun 2024To evaluate cytokine levels of interleukin (IL)-1β, IL-4, IL-6, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the gingival crevicular fluid (GCF)...
OBJECTIVE
To evaluate cytokine levels of interleukin (IL)-1β, IL-4, IL-6, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the gingival crevicular fluid (GCF) of periodontal sites in individuals with Down syndrome (DS) and analyze their relationship with clinical periodontal parameters.
MATERIALS AND METHODS
A cross-sectional study was conducted with 49 DS patients and 32 individuals without DS (non-DS group). Periodontal probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and visible plaque index (VPI) were evaluated. The periodontal sites were classified as shallow, moderate, and deep. GCF was collected in all shallow sites and, when present, in moderate and deep sites for the analysis of cytokine levels. The cytokines, IL-1β, IL-4, IL-6, IL-17a, TNF-α, and IFN-γ, were quantified using the Luminex® automatic analyzer system.
RESULTS
The DS group presented greater severity of periodontitis compared to the non-DS group (P = 0.005). The DS group showed a significant direct correlation of IL-1β and an inverse correlation of IFN-γ and IL-14 with all periodontal variables. In the analysis stratified by periodontal pocket depth, we observed a higher level of IFN-γ, IL-17a, IL-1β, and IL-6 in the shallow sites, and IL-17a, IL-1β, and IL-6 in deep pockets of DS group individuals. Multivariate models showed that higher levels of IL-1β, IL-4, IL-6, and IL-17a were associated with Down syndrome even after adjusting for periodontal status, sex, and age.
CONCLUSION
The findings suggest that people with DS have greater periodontal impairment and higher levels of cytokines in GCF, even in sites having clinical periodontal parameters similar to those of individuals without DS. These data reiterate the concept of an altered and less effective immune response in the population with DS in the face of a periodontal microbial challenge.
CLINICAL RELEVANCE
Elevated periodontal inflammation burden can be observed with higher cytokine levels in the gingival crevicular fluid of people with Down syndrome, especially IL-1, IL-4, IL-6, and IL-17, regardless of the stage of periodontitis.
Topics: Humans; Gingival Crevicular Fluid; Cross-Sectional Studies; Male; Female; Down Syndrome; Cytokines; Periodontal Index; Adult; Dental Plaque Index; Adolescent
PubMed: 38907162
DOI: 10.1007/s00784-024-05789-x -
The Lancet. Digital Health Jul 2024Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used...
A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts.
BACKGROUND
Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery.
METHODS
Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a composite of pneumonia, acute respiratory distress syndrome, and unexpected mechanical ventilation. Model development with candidate predictor variables was done in the GlobalSurg-CovidSurg Week dataset (global; October, 2020). Two structured machine learning techniques were explored (XGBoost and the least absolute shrinkage and selection operator [LASSO]), and the model with the best performance (GSU-Pulmonary Score) underwent internal validation using bootstrap resampling. The discrimination and calibration of the score were externally validated in two further prospective cohorts: CovidSurg-Cancer (worldwide; February to August, 2020, during the COVID-19 pandemic) and RECON (UK and Australasia; January to October, 2019, before the COVID-19 pandemic). The model was deployed as an online web application. The GlobalSurg-CovidSurg Week and CovidSurg-Cancer studies were registered with ClinicalTrials.gov, NCT04509986 and NCT04384926.
FINDINGS
Prognostic models were developed from 13 candidate predictor variables in data from 86 231 patients (1158 hospitals in 114 countries). External validation included 30 492 patients from CovidSurg-Cancer (726 hospitals in 75 countries) and 6789 from RECON (150 hospitals in three countries). The overall rates of pulmonary complications were 2·0% in derivation data, and 3·9% (CovidSurg-Cancer) and 4·7% (RECON) in the validation datasets. Penalised regression using LASSO had similar discrimination to XGBoost (area under the receiver operating curve [AUROC] 0·786, 95% CI 0·774-0·798 vs 0·785, 0·772-0·797), was more explainable, and required fewer covariables. The final GSU-Pulmonary Score included ten predictor variables and showed good discrimination and calibration upon internal validation (AUROC 0·773, 95% CI 0·751-0·795; Brier score 0·020, calibration in the large [CITL] 0·034, slope 0·954). The model performance was acceptable on external validation in CovidSurg-Cancer (AUROC 0·746, 95% CI 0·733-0·760; Brier score 0·036, CITL 0·109, slope 1·056), but with some miscalibration in RECON data (AUROC 0·716, 95% CI 0·689-0·744; Brier score 0·045, CITL 1·040, slope 1·009).
INTERPRETATION
This novel prognostic risk score uses simple predictor variables available at the time of a decision for elective surgery that can accurately stratify patients' risk of postoperative pulmonary complications, including during SARS-CoV-2 outbreaks. It could inform surgical consent, resource allocation, and hospital-level prioritisation as elective surgery is upscaled to address global backlogs.
FUNDING
National Institute for Health Research.
Topics: Humans; Elective Surgical Procedures; Postoperative Complications; Female; Prognosis; Middle Aged; Male; Prospective Studies; Aged; COVID-19; Risk Assessment; Adult; Machine Learning; Risk Factors; Lung Diseases; Cohort Studies
PubMed: 38906616
DOI: 10.1016/S2589-7500(24)00065-7 -
International Journal of Biological... Jun 2024Cell migration regulated by Thrombospondin 2 (THSB2) is important for the development of pulmonary artery remodeling, but the mechanism by which THBS2-mediated cell...
Cell migration regulated by Thrombospondin 2 (THSB2) is important for the development of pulmonary artery remodeling, but the mechanism by which THBS2-mediated cell migration regulates the development of pulmonary artery remodeling in broiler ascites syndrome (AS) is unclear. In addition, the lack of chicken THBS2 antibodies makes it difficult to study the mechanism in depth. In our study, we used recombinant gene technology, protein purification, and other techniques to obtain mouse anti-chicken THBS2 antibody and analyze its expression in broilers, ascites broilers and other animals. The results showed that we immunized mouse with recombinant THBS2 protein and obtained an antibody titer of 1:204,800, and the addition of astragalus polysaccharide as an immunomodulator during immunization significantly increased the titer of the antibody. Western blotting (WB) and immunofluorescence results showed that the THBS2 was significantly down-regulated in the ascites broiler. The THBS2 antibody we prepared can also detect THBS2 protein in duck, mouse, goat, and rabbit tissues. These results provide a foundation for further investigation of the role of THBS2 in pulmonary artery remodeling in broiler ascites syndrome and a powerful tool for studying the role of THBS2 in AS.
PubMed: 38906344
DOI: 10.1016/j.ijbiomac.2024.133284 -
Journal of Ethnopharmacology Jun 2024Ischemic stroke is a serious disabling and fatal disease that places a heavy burden on the world. Stroke induces a state of systemic immunosuppression that is strongly...
ETHNOPHARMACOLOGICAL RELEVANCE
Ischemic stroke is a serious disabling and fatal disease that places a heavy burden on the world. Stroke induces a state of systemic immunosuppression that is strongly associated with an increased risk of infection and severe outcomes. Buyang Huanwu Decoction (BYHWD) is an ancient Chinese traditional formula with a good clinical and experimental basis. However, the role of BYHWD on post-stroke immunomodulation, especially immunosuppression, is unclear.
AIM OF THE STUDY
The aim of this study was to investigate the pharmacological mechanism of BYHWD to alleviate ischemic stroke by analyzing splenic T cells apoptosis triggered by the AIM2 inflammasome activation cascade.
MATERIALS AND METHODS
An ischemic stroke model in C57BL/6 J mice was constructed using the MCAO method. The mNSS test and the hanging wire test were conducted to evaluate neurological impairment in mice. Histopathological damage was visualized by Nissl staining and HE staining. The protective effects of BYHWD on the spleen were determined by splenic index and spleen HE staining. The inhibition of AIM2 inflammasome cascade by BYHWD were explored through immunofluorescence (IF), flow cytometry, enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Flow cytometry was used to assess the apoptosis of splenic T cells.
RESULTS
BYHWD significantly reduced infarct size, improved neurological function scores, and alleviated histopathological damage in middle cerebral artery occlusion (MCAO) mice. At the same time, BYHWD salvaged spleen atrophy. BYHWD significantly ameliorated apoptosis of splenic T lymphocytes. Key proteins and factors in the AIM2/IL-1β/FasL/Fas axis are effectively inhibited from expression after BYHWD treatment.
CONCLUSION
It is the first study to demonstrate that BYHWD can improve stroke-induced immunosuppression by down-regulating Fas-dependent splenic T-cell apoptosis triggered by peripheral AIM2 inflammasome-driven signaling cascade.
PubMed: 38906338
DOI: 10.1016/j.jep.2024.118474 -
Chemico-biological Interactions Aug 2024Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Life-threatening medical conditions characterized by high morbidity and mortality rates, where...
Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury by modulating heat shock protein A12B to inhibit the toll-like receptor 4/nuclear factor-kappa B signaling pathway.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Life-threatening medical conditions characterized by high morbidity and mortality rates, where the inflammatory process plays a crucial role in lung tissue damage, especially in models induced by lipopolysaccharide (LPS). Heat shock protein A12B (HSPA12B) has strong anti-infammatory properties However, it is unknown whether increased HSPA12B is protective against LPS-induced ALI. And Dexmedetomidine (DEX) is a potent α-adrenergic receptor (α-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. This study utilized bioinformatics analysis and an LPS-induced ALI model to explore how DEX alleviates lung injury by modulating HSPA12B and inhibiting the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Results indicate that HSPA12B overexpression and DEX pre-treatment markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) in the BALF, and the levels of NO, MDA,SOD and MPO in the lung. Moreover, HSPA12B overexpression and DEX pre-treatment significantly reduces lung injury and inflammation levels by upregulating HSPA12B and inhibiting the activation of the TLR4/NF-κB signaling pathway. On the contrary, when the expression of HSPA12B is inhibited, the protective effect of DEX pre-treatment on lung tissue is significantly weakened.In summary, our research demonstrated that the increased expression of AAV-mediated HSPA12B in the lungs of mice inhibits acute inflammation and suppresses the activation of TLR4/NF-κB pathway in a murine model of LPS-induced ALI. DEX could enhance HSPA12B and inhibit the initiation and development of inflammation through down-regulating TLR4/NF-κB pathway.These findings highlight the potential of DEX as a therapeutic agent for treating ALI and ARDS, offering new strategies for clinical intervention.
Topics: Dexmedetomidine; Acute Lung Injury; Animals; Lipopolysaccharides; Toll-Like Receptor 4; NF-kappa B; Signal Transduction; HSP70 Heat-Shock Proteins; Mice; Male; Mice, Inbred C57BL; Lung; Interleukin-1beta
PubMed: 38901789
DOI: 10.1016/j.cbi.2024.111112 -
Current Biology : CB Jun 2024Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity...
Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse postsubiculum (PoSub), where a majority of neurons are modulated by the animal's head direction, was sequentially activated along the dorsoventral axis during sleep at the transition from hyperpolarized "DOWN" to activated "UP" states, while representing a stable direction. Computational modeling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated currents (I), which we confirmed in ex vivo slice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of I across cortical neurons could result in sequential neuronal patterns and that traveling activity upstream of the entorhinal-hippocampal circuit organizes large-scale neuronal activity supporting learning and memory during sleep.
PubMed: 38901427
DOI: 10.1016/j.cub.2024.05.048 -
Blood Jun 2024
Topics: Down Syndrome; Humans; Proto-Oncogene Proteins c-myc; Male; Female
PubMed: 38900477
DOI: 10.1182/blood.2024024595