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Theranostics 2024It has been emergingly recognized that apoptosis generates plenty of heterogeneous apoptotic vesicles (apoVs), which play a pivotal role in the maintenance of organ and...
It has been emergingly recognized that apoptosis generates plenty of heterogeneous apoptotic vesicles (apoVs), which play a pivotal role in the maintenance of organ and tissue homeostasis. However, it is unknown whether apoVs influence postnatal ovarian folliculogenesis. Apoptotic pathway deficient mice including Fas mutant ( ) and Fas ligand mutant ( ) mice were used with apoV replenishment to evaluate the biological function of apoVs during ovarian folliculogenesis. Ovarian function was characterized by morphological analysis, biochemical examination and cellular assays. Mechanistical studies were assessed by combinations of transcriptomic and proteomic analysis as well as molecular assays. mice was established to verify the role of WNT signaling during ovarian folliculogenesis. Polycystic ovarian syndrome (PCOS) mice and 15-month-old mice were used with apoV replenishment to further validate the therapeutic effects of apoVs based on WNT signaling regulation. We show that systemic administration of mesenchymal stem cell (MSC)-derived apoptotic vesicles (MSC-apoVs) can ameliorate impaired ovarian folliculogenesis, PCOS phenotype, and reduced birth rate in and mice. Mechanistically, transcriptome analysis results revealed that MSC-apoVs downregulated a number of aberrant gene expression in mice, which were enriched by kyoto encyclopedia of genes and genomes (KEGG) pathway analysis in WNT signaling and sex hormone biosynthesis. Furthermore, we found that apoptotic deficiency resulted in aberrant WNT/β-catenin activation in theca and mural granulosa cells, leading to responsive action of dickkopf1 (DKK1) in the cumulus cell and oocyte zone, which downregulated WNT/β-catenin expression in oocytes and, therefore, impaired ovarian folliculogenesis NPPC/cGMP/PDE3A/cAMP cascade. When WNT/β-catenin was specially activated in theca cells of mice, the same ovarian impairment phenotypes observed in apoptosis-deficient mice were established, confirming that aberrant activation of WNT/β-catenin in theca cells caused the impairment of ovarian folliculogenesis. We firstly revealed that apoVs delivered WNT membrane receptor inhibitor protein RNF43 to ovarian theca cells to balance follicle homeostasis through vesicle-cell membrane integration. Systemically infused RNF43-apoVs down-regulated aberrantly activated WNT/β-catenin signaling in theca cells, contributing to ovarian functional maintenance. Since aging mice have down-regulated expression of WNT/β-catenin in oocytes, we used MSC-apoVs to treat 15-month-old mice and found that MSC-apoVs effectively ameliorated the ovarian function and fertility capacity of these aging mice through rescuing WNT/β-catenin expression in oocytes. Our studies reveal a previously unknown association between apoVs and ovarian folliculogenesis and suggest an apoV-based therapeutic approach to improve oocyte function and birth rates in PCOS and aging.
Topics: Animals; Female; Polycystic Ovary Syndrome; Mice; Wnt Signaling Pathway; Mesenchymal Stem Cells; Apoptosis; Ovarian Follicle; Ovary; Disease Models, Animal; Aging; Fas Ligand Protein
PubMed: 38855175
DOI: 10.7150/thno.94943 -
MedRxiv : the Preprint Server For... Jun 2024The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of...
The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain development. We utilized longitudinal resting-state EEG data from 457 typically developing infants, comprising 938 recordings, to develop age prediction models. The multilayer perceptron model demonstrated the highest accuracy with an R2 of 0.82 and a mean absolute error of 92.4 days. Aperiodic offset and periodic theta, alpha, and beta power were identified as key predictors of age via Shapley values. Application of the model to EEG data from infants later diagnosed with autism spectrum disorder or Down syndrome revealed significant underestimations of chronological age. This study establishes the feasibility of using EEG to assess brain maturation in early childhood and supports its potential as a clinical tool for early identification of alterations in brain development.
PubMed: 38853932
DOI: 10.1101/2024.05.31.24308275 -
International Journal of Surgery Case... Jul 2024Cerebral fat embolism syndrome is a rare complication of long bone fractures, often overlooked and found in late stages. We present patient with a late recognition of...
INTRODUCTION AND IMPORTANCE
Cerebral fat embolism syndrome is a rare complication of long bone fractures, often overlooked and found in late stages. We present patient with a late recognition of Cerebral Fat Embolism with Large vessel occlusion post femoral internal fixation.
CASE PRESENTATION
An elderly female suffered right intertrochanteric fracture after falling down. Open reduction internal fixation with Interlocking plate was performed at the fifth day. Upon returning to the ward, the patient did not regain full consciousness and apparent right hemiparesis were observed. A head Computed Tomography was performed and found left hemisphere ischemia consistent with middle cerebral artery occlusion. The patient condition worsened and died 3 days postoperatively.
CLINICAL DISCUSSION
Cases of fat embolism that occur purely isolated in the brain are rare cases that occur after internal fixation of the femur, so they are often not noticed by clinicians. Several factors can increase the risk of the event, delay in fixation and diabetes mellitus which was found in our patient could increase the risk of fat emboli syndrome. Apart from that, osteoporosis also increases the risk of fat embolism syndrome that was found in our subject.
CONCLUSIONS
Cerebral Large Vessel Occlusion Fat Embolism Syndrome is rare case occur following internal fixation. There is a need for early recognition to be carried out to treat early or prevent the occurrence of fat embolism.
PubMed: 38852560
DOI: 10.1016/j.ijscr.2024.109828 -
Atlantoaxial dislocation due to Os odontoideum in down syndrome: Literature review and case reports.International Journal of Surgery Case... Jul 2024Os odontoideum is a rare condition commonly associated with atlantoaxial instability (AAI) and leading to atlantoaxial dislocation. The incidence of Os odontoideum is...
INTRODUCTION AND IMPORTANCE
Os odontoideum is a rare condition commonly associated with atlantoaxial instability (AAI) and leading to atlantoaxial dislocation. The incidence of Os odontoideum is higher in patients with Down syndrome. Similar to odontoid fractures, atlantoaxial dislocation in patients with Os odontoideum can result in neurological deficits, disability, and even mortality.
CASE PRESENTATION
We present two cases of Os odontoideum accompanied by Down syndrome. Both patients were hospitalized due to progressive tetraparesis after falls several months prior. Upon examination, the patients exhibited myelopathy and were unable to walk or stand. MRI revealed spinal stenosis at the C1-C2 level due to atlantoaxial dislocation. C1-C2 fixation using Harms' technique was performed in both cases. One case experienced a complication involving instrument failure, necessitating revision surgery.
CLINICAL DISCUSSION
Due to the characteristics of transverse ligament laxity, low muscle tone, excessive joint flexibility, and cognitive impairment, children with both Down syndrome and Os odontoideum are at a high risk of disability and even mortality from spinal cord injury. Most authors recommend surgical management when patients exhibit atlantoaxial instability. Additional factors such as low bone density, cognitive impairment, and a high head-to-body ratio may increase the risk of surgical instrument failure and nonunion postoperatively in patients with Down syndrome.
CONCLUSION
Os odontoideum is a cause of AAI in patients with DS. Indication of surgery in the presence of AAI helps to resolve neurological injury and prevent further deterioration. The use of a cervical collar is considered to prevent instrument failure postoperatively.
PubMed: 38852555
DOI: 10.1016/j.ijscr.2024.109888 -
NPJ Microgravity Jun 2024Lower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with...
Lower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). This study quantifies the effect of LBNP on intraocular pressure (IOP), mean arterial pressure at eye level (MAP), and ocular perfusion pressure (OPP). Twenty-four subjects (12 male, 12 female) were subjected to graded LBNP in 0° supine and 15° head-down tilt (HDT) postures from 0 mmHg to -50 mmHg in 10 mmHg increments. IOP decreased significantly with LBNP pressure in 0° supine (by 0.7 ± 0.09 mmHg per 10 mmHg LBNP pressure, p < 0.001) and in 15° HDT (by 1.0 ± 0.095 mmHg per 10 mmHg of LBNP pressure, p < 0.001). MAP significantly decreased by 0.9 ± 0.4 mmHg per 10 mmHg of LBNP pressure in 0° supine (p = 0.016) but did not significantly change with LBNP in 15° HDT (p = 0.895). OPP did not significantly change with LBNP in 0° supine (p = 0.539) but it significantly increased in 15° HDT at 1.0 ± 0.3 mmHg per 10 mmHg of LBNP pressure (p = 0.010). Sex did not have a significant effect on OPP, MAP, or IOP in any condition. In 15° HDT, the reduction in IOP during increasing negative pressure, combined with the relatively constant MAP, led to the increase in OPP. Furthermore, results suggest that LBNP, while effective in reducing IOP, is not effective in reducing OPP across all postures investigated.
PubMed: 38851800
DOI: 10.1038/s41526-024-00404-5 -
Science Advances Jun 2024Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental and acute phenotypes in terminal cell types. Which phenotypes remain...
Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental and acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this question in a model of DS neurogenesis, we derived trisomy 21 (T21) human induced pluripotent stem cells (iPSCs) alongside, otherwise, isogenic euploid controls from mosaic DS fibroblasts and equipped one chr21 copy with an inducible transgene. Monoallelic chr21 silencing by is near-complete and irreversible in iPSCs. Differential expression reveals that T21 neural lineages and iPSCs share suppressed translation and mitochondrial pathways and activate cellular stress responses. When is induced before the neural progenitor stage, T21 dosage correction suppresses a pronounced skew toward astrogenesis in neural differentiation. Because our transgene remains inducible in postmitotic T21 neurons and astrocytes, we demonstrate that efficiently represses genes even after terminal differentiation, which will empower exploration of cell type-specific T21 phenotypes that remain responsive to chr21 dosage.
Topics: Down Syndrome; Humans; Neurogenesis; Induced Pluripotent Stem Cells; Gene Dosage; RNA, Long Noncoding; Cell Differentiation; Chromosomes, Human, Pair 21; Neurons
PubMed: 38848354
DOI: 10.1126/sciadv.adj0385 -
Australian Critical Care : Official... Jun 2024Cognitive impairment poses a significant challenge following critical illness in the intensive care unit. A knowledge gap exists concerning how patients experience...
BACKGROUND
Cognitive impairment poses a significant challenge following critical illness in the intensive care unit. A knowledge gap exists concerning how patients experience cognitive impairments.
OBJECTIVES
The aim was to explore patients' and relatives' experiences of patients' cognitive impairment due to critical illness following an intensive care unit admission.
METHODS
A qualitative multicentre study was conducted in Denmark with 3- and 6-month follow-ups using single and dyadic interviews. A phenomenological hermeneutic approach was adopted using a Ricoeur-inspired textual in-depth analysis method. The Consolidated Criteria for Reporting Qualitative Research checklist was used.
RESULTS
Three themes emerged from interviews with 18 patients and 14 relatives: 'It feels like living in a parallel world', 'Getting back to a normal everyday life with a vulnerable self', and 'Managing everyday life using self-invented strategies'. Patients used self-invented strategies to manage their vulnerability and newly acquired cognitive impairments when no help or support was provided specifically targeting their cognitive impairments. Not being as cognitively capable as they previously had been turned their lives upside down. Losing control and not being themselves made them vulnerable. Patients did not want to burden others. However, support from relatives was invaluable in their recovery and rehabilitation.
CONCLUSIONS
Patients experienced multiple cognitive impairments affecting their adaption to everyday life. They strove to overcome their vulnerability using a variety of self-invented strategies and activities.
PubMed: 38839438
DOI: 10.1016/j.aucc.2024.05.004