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Journal of Innate Immunity May 2024Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in... (Review)
Review
Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis respectively undergo substantial activation after sepsis. Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation", which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.
PubMed: 38815564
DOI: 10.1159/000539502 -
Scientific Reports May 2024Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular...
Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms.
Topics: Humans; Down Syndrome; Alzheimer Disease; Female; Male; Adult; Aged; Middle Aged; Cerebrovascular Disorders; Magnetic Resonance Imaging; Risk Factors; White Matter; Age Factors; Aging; tau Proteins
PubMed: 38811657
DOI: 10.1038/s41598-024-61962-y -
Science Advances May 2024Surface plasmons have proven their ability to boost the sensitivity of mid-infrared hyperspectral imaging by enhancing light-matter interactions. Surface phonons, a...
Surface plasmons have proven their ability to boost the sensitivity of mid-infrared hyperspectral imaging by enhancing light-matter interactions. Surface phonons, a counterpart technology to plasmons, present unclear contributions to hyperspectral imaging. Here, we investigate this by developing a plasmon-phonon hyperspectral imaging system that uses asymmetric cross-shaped nanoantennas composed of stacked plasmon-phonon materials. The phonon modes within this system, controlled by light polarization, capture molecular refractive index intensity and lineshape features, distinct from those observed with plasmons, enabling more precise and sensitive molecule identification. In a deep learning-assisted imaging demonstration of severe acute respiratory syndrome coronavirus (SARS-CoV), phonons exhibit enhanced identification capabilities (230,400 spectra/s), facilitating the de-overlapping and observation of the spatial distribution of two mixed SARS-CoV spike proteins. In addition, the plasmon-phonon system demonstrates increased identification accuracy (93%), heightened sensitivity, and enhanced detection limits (down to molecule monolayers). These findings extend phonon polaritonics to hyperspectral imaging, promising applications in imaging-guided molecule screening and pharmaceutical analysis.
PubMed: 38809968
DOI: 10.1126/sciadv.ado3179 -
CoDAS 2024To investigate oropharyngeal structures and functions in a pediatric population with Down Syndrome (DS) and obstructive sleep apnea (OSA) and to correlate with the...
PURPOSE
To investigate oropharyngeal structures and functions in a pediatric population with Down Syndrome (DS) and obstructive sleep apnea (OSA) and to correlate with the apnea/hypopnea index (AHI) and sleep questionnaires.
METHODS
12 Children with DS and OSA, between the age of 4 and 12 years old, underwent polysomnography (PSG); sleep questionnaires, Pediatric Sleep Questionnaire (PSQ) and Obstructive Sleep Apnea-18 (OSA-18); and speech-language evaluation using the Short Evaluation of Orofacial Myofunctional Protocol (ShOM).
RESULTS
There was a positive correlation between ShoM higher scores and the apnea-hypopnea index (AHI) and between ShoM and the number of hypopneas. The orofacial myofunctional alterations observed in the studied group were: oral breathing, alteration in lip tonus and competence, tongue posture at rest and in swallowing, and occlusal alteration. There was also an increased risk for OSA according to the sleep questionnaires, as well as the presence of obesity and overweight, but without correlation with the severity of OSA.
CONCLUSION
All DS children show alterations in orofacial characteristics, higher scores being associated to severe OSA. Orofacial myofunctional evaluation may help to identify different phenotypes in Down syndrome children with Obstructive sleep Apnea, enhancing the need for a multidisciplinary approach.
Topics: Humans; Down Syndrome; Sleep Apnea, Obstructive; Child; Pilot Projects; Polysomnography; Male; Female; Child, Preschool; Surveys and Questionnaires; Severity of Illness Index; Mouth Breathing; Tongue; Facial Muscles; Cross-Sectional Studies
PubMed: 38808857
DOI: 10.1590/2317-1782/20242023119pt -
Cureus Apr 2024Down syndrome often coincides with hypothyroidism, a condition that may lead to pericardial effusion (PE), though cardiac tamponade remains an infrequent complication....
Down syndrome often coincides with hypothyroidism, a condition that may lead to pericardial effusion (PE), though cardiac tamponade remains an infrequent complication. Cardiac tamponade is an emergency that requires immediate diagnosis and treatment. Here, we present a case of a patient who presented to the emergency department (ED) with Down syndrome associated with hypothyroidism and underwent immediate pericardiocentesis and pericardial window placement. A 52-year-old male, with a history of Down's syndrome and hypothyroidism, presented to the ED complaining of shortness of breath and chest pain. He had previously been diagnosed with PE. On examination, he exhibited average heart rate, low blood pressure, decreased heart sounds, and jugular venous distention, with no murmur or frictional rub. Initial investigations revealed normal sinus rhythm on EKG but an enlarged cardiac silhouette on chest X-ray. Laboratory tests showed elevated C-reactive protein and sedimentation rate, suggestive of inflammation, while arterial blood gas showed compensated respiratory alkalosis. Thyroid-stimulating hormone (TSH) was elevated. Despite supplemental oxygen, the patient's condition worsened, prompting a bedside ultrasound revealing cardiac tamponade. A cardiology consultation recommended immediate transfer for treatment. At a different hospital, pericardiocentesis was performed, followed by the placement of a pericardial window to prevent recurrence. Follow-up imaging showed improvement in pleural effusion and resolution of cardiac tamponade. The patient's symptoms improved, and he was discharged with regular follow-up. Down's syndrome is a chromosomal disorder characterized by the trisomy of chromosome 21. It is associated with various cardiac complications. Such patients have an elevated risk of PE due to a variety of reasons, such as viral infections, hypothyroidism, or autoimmune diseases. Although PE has been found, the incidence of cardiac tamponade has rarely been reported. The pathogenesis of PE in hypothyroidism is due to the leakage of fluids from the capillaries and the build-up of fluid in the pericardial space. The treatment of PE is treating hypothyroidism with thyroxine. In rare cases like ours, when the patient develops cardiac tamponade, the patient often needs pericardiocentesis. Our patient had to undergo pericardial window placement, as well to prevent recurrent symptoms. In conclusion, this case report sheds light on the occurrence of cardiac tamponade in a patient with Down's syndrome and hypothyroidism, a relatively rare complication that necessitates prompt recognition and intervention. Through this report, we emphasize the importance of considering cardiac tamponade in the differential diagnosis of patients with Down's syndrome presenting with symptoms suggestive of cardiovascular compromise.
PubMed: 38803753
DOI: 10.7759/cureus.59023 -
Acta Neuropathologica May 2024The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for...
The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.
Topics: Humans; Down Syndrome; Alzheimer Disease; COVID-19; Male; Female; Aged; Middle Aged; Brain; Aged, 80 and over; Astrocytes; Amyloid beta-Peptides; SARS-CoV-2; Microglia; Adult; tau Proteins
PubMed: 38801558
DOI: 10.1007/s00401-024-02743-9 -
MedRxiv : the Preprint Server For... May 2024Numerous research groups worldwide have focused on postmortem imaging to bridge the resolution gap between clinical neuroimaging and neuropathology data. We developed a...
Numerous research groups worldwide have focused on postmortem imaging to bridge the resolution gap between clinical neuroimaging and neuropathology data. We developed a standardized protocol for brain embedding, imaging, and processing, facilitating alignment between antemortem MRI, postmortem MRI, and pathology to observe brain atrophy and structural damage progression over time. Using 7T postmortem ex vivo MRI, we explore the potential correlation of amygdala and hippocampal atrophy with neuropathological burden in both Down syndrome (DS) and Alzheimer's disease (AD) cohorts. Using 7T postmortem ex vivo MRI scans from 66 cases (12 DS and 54 AD) alongside a subset of antemortem scans (n=17), we correlated manually segmented hippocampal and amygdala volumes, adjusted for age, sex, and ApoE4 status, with pathological indicators such as Thal phase, Braak stage, limbic-predominant age-related TDP-43 encephalopathy (LATE) stage, hippocampal sclerosis (HS), and Lewy body (LB) stage. A significant correlation was observed between postmortem and antemortem volumes for the hippocampus, but a similar trend observed for the amygdala did not reach statistical significance. DS individuals exhibited notably smaller hippocampal and amygdala volumes compared to AD subjects. In DS, lower hippocampal and amygdala volumes correlated with more severe Braak stage, without significant associations with Thal phase. LATE and HS pathologies were uncommon in DS cases but trended toward smaller hippocampal volumes. In AD, lower hippocampal volume associated with dementia duration, advanced Thal phase, Braak stage, LATE stage, and HS presence, whereas reduced amygdala volume correlated mainly with severe LATE stage and HS, but not with Thal or Braak stages. No significant LB correlation was detected in either DS or AD cohorts. Hippocampal volume in AD appears influenced by both AD and LATE pathologies, while amygdala volume seems primarily influenced by LATE. In DS, smaller hippocampal volume, relative to AD, appears primarily influenced by tau pathology.
PubMed: 38798514
DOI: 10.1101/2024.05.15.24307354 -
Mathematical Biosciences May 2024This paper develops a theory for anaphase in cells. After a brief description of microtubules, the mitotic spindle and the centrosome, a mathematical model for anaphase...
This paper develops a theory for anaphase in cells. After a brief description of microtubules, the mitotic spindle and the centrosome, a mathematical model for anaphase is introduced and developed in the context of the cell cytoplasm and liquid crystalline structures. Prophase, prometaphase and metaphase are then briefly described in order to focus on anaphase, which is the main study of this paper. The entities involved are modelled in terms of liquid crystal defects and microtubules are represented as defect flux lines. The mathematical techniques employed make extensive use of energy considerations based on the work that was developed by Dafermos (1970) from the classical Frank-Oseen nematic liquid crystal energy (Frank, 1958; Oseen, 1933). With regard to liquid crystal theory we introduce the concept of regions of influence for defects which it is believed have important implications beyond the subject of this paper. The results of this paper align with observed biochemical phenomena and are explored in application to HeLa cells and Caenorhabditis elegans. This unified approach offers the possibility of gaining insight into various consequences of mitotic abnormalities which may result in Down syndrome, Hodgkin lymphoma, breast, prostate and various other types of cancer.
PubMed: 38795952
DOI: 10.1016/j.mbs.2024.109219 -
Medicina (Kaunas, Lithuania) Apr 2024The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a...
The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.
Topics: Humans; Down Syndrome; Male; Female; Uveitis; Child; Retrospective Studies; Child, Preschool; Adolescent; Infant; Databases, Factual; Incidence; Cohort Studies; Risk Factors; Risk Assessment
PubMed: 38792893
DOI: 10.3390/medicina60050710 -
International Journal of Environmental... May 2024Down syndrome (DS) is characterised by a duplication of chromosome-21 and is linked to co-occurring physical and mental health conditions, including low self-efficacy...
Down syndrome (DS) is characterised by a duplication of chromosome-21 and is linked to co-occurring physical and mental health conditions, including low self-efficacy and disturbed mood states. The purpose of this study was to investigate the effects of an eight-week prescribed physical and/or cognitive training intervention on measures of mood disturbance, life satisfaction and self-efficacy in a population of adults with DS. Eighty-three participants (age 27.1 ± 8.0 years) from across five continents volunteered. Participants were assigned using matched groups based upon performance in a modified six-minute walk test to either an exercise (EXE) 3 × 30 min of walking/jogging per week, cognitive training (COG) 6 × 20 min per week, a combined group (COM) or the control (CON) who did not complete any intervention. Profile of Mood States (POMS) were assessed using a five-point scale across 65 categories pre- and post-study as well as upon completion of each week of the intervention. In addition, Satisfaction with Life Scale (SWLS) and self-efficacy using the Generalised Self-Efficacy scale (GSE) were recorded before and after the intervention. GSE increased for all participants by 1.9 ± 5.2 ( = 0.002) from pre- to post-intervention, while POMS showed significant changes for the whole group from pre- to post-intervention for tension ( < 0.001), depression ( < 0.001) and for anger ( < 0.001). In addition, significant correlations were observed between SWLS and ΔTMD, Δtension, Δanger, and Δfatigue ( < 0.05) for EXE. Both COG and EXE provide a framework for empowering enhancements in life satisfaction, self-efficacy and mood states fostering improvements in quality of life.
Topics: Humans; Self Efficacy; Adult; Male; Female; Affect; Personal Satisfaction; Young Adult; Down Syndrome; Exercise; Cognition; Quality of Life; Adolescent
PubMed: 38791824
DOI: 10.3390/ijerph21050610