ABSTRACT
The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a pre-existing mother. Here, we show that a Plk4 oscillation at the base of the growing centriole initiates and times centriole biogenesis to ensure that centrioles grow at the right time and to the right size. The Plk4 oscillation is normally entrained to the cell-cycle oscillator but can run autonomously of it-potentially explaining why centrioles can duplicate independently of cell-cycle progression. Mathematical modeling indicates that the Plk4 oscillation can be generated by a time-delayed negative feedback loop in which Plk4 inactivates the interaction with its centriolar receptor through multiple rounds of phosphorylation. We hypothesize that similar organelle-specific oscillations could regulate the timing and execution of organelle biogenesis more generally.
Subject(s)
Biological Clocks/physiology , Centrioles/metabolism , Drosophila Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Animals , Cell Cycle/physiology , Cell Cycle Proteins/metabolism , Centrosome/metabolism , Drosophila Proteins/physiology , Drosophila melanogaster/metabolism , Organelle Biogenesis , Phosphorylation , Protein Serine-Threonine Kinases/physiologyABSTRACT
Many cells localize mRNAs to discrete locations in the cytoplasm. Coupled to local translation, this process affords precise spatial and temporal control of protein function. This SnapShot provides an overview of the key events in subcellular mRNA localization and highlights recent progress in understanding how cytoskeletal motors orchestrate mRNA trafficking.
Subject(s)
RNA, Messenger/analysis , RNA, Messenger/genetics , Active Transport, Cell Nucleus , Animals , Fungi/cytology , Fungi/metabolism , Protein Biosynthesis , RNA Processing, Post-Transcriptional , RNA, Messenger/metabolismABSTRACT
Centrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that in Drosophila embryos an oscillation of Polo-like kinase 4 (Plk4) helps to initiate and time the growth of the cartwheel at the proximal end. Here, in the same model, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels rise and fall as the new centriole MTs grow, in a manner that appears to be entrained by the core cyclin-dependent kinase (Cdk)-Cyclin oscillator that drives the nuclear divisions in these embryos. These CP110 and Cep97 dynamics, however, do not appear to time the period of centriole MT growth directly. Instead, we find that changing the levels of CP110 and Cep97 appears to alter the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected potential crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which might help to coordinate centriole growth. This article has an associated First Person interview with the first authors of the paper.
Subject(s)
Centrioles , Microtubule-Associated Proteins , Phosphoproteins/metabolism , Animals , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Centrioles/metabolism , Drosophila/metabolism , Humans , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Microtubules/metabolism , Protein Serine-Threonine Kinases/geneticsABSTRACT
INTRODUCTION: Endovascular thrombectomy (EVT) is the standard of care for patients with large-vessel occlusion acute ischemic stroke (AIS). There may be differing recanalization effectiveness based on patients' sex, and understanding such variations can improve patient outcomes by adjusting for differences. We aimed to assess the sex differences in outcome after EVT for patients with AIS. METHODS: We retrospectively analyzed 250 consecutive AIS patients who underwent EVT from July 2019 to February 2022 across two large comprehensive tertiary care stroke centers in China. Outcomes of male patients were compared to females, where poor outcome was defined as a modified Rankin score (mRS) of 3-6 at 90 days. RESULTS: Male patients had higher rates of symptomatic intracranial hemorrhage (sICH) (12.50% vs. 4.05%, p = 0.042) and higher hospitalization costs (114,541.08 vs. 105,790.27 RMB, p = 0.024). Male patients also had a longer median onset-to-needle time (ONT) (146.00 [104.00, 202.00] versus 120.00 [99.25, 144.75], p = 0.026). However, there were no differences in hospitalization length (p = 0.251), 90-day favorable outcome (p = 0.952), and 90-day mortality (p = 0.931) between the sexes. CONCLUSION: Female patients had lower hospitalization costs and sICH rates than males after EVT for AIS. Identifying such differences and implementing measures, including adaptations to workflow optimization, would help to reduce the ONT and last known normal-to-puncture time seen in males to improve patient outcomes. Despite such variations, favorable outcomes and mortality are similar in female and male AIS patients.
Subject(s)
Endovascular Procedures , Ischemic Stroke , Thrombectomy , Humans , Male , Female , Ischemic Stroke/surgery , Thrombectomy/methods , Endovascular Procedures/methods , Aged , Middle Aged , Retrospective Studies , Sex Factors , Treatment Outcome , China , Aged, 80 and over , Sex CharacteristicsABSTRACT
OBJECTIVE: Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. METHODS: 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. RESULTS: The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16-25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. CONCLUSION: Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.
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AIMS: This study aimed to systematically review the literature on neuroanatomical predictors of future problematic drinking in adolescents. METHODS: Using PRISMA guidelines, a systematic review was conducted to evaluate neuroanatomical predictors of problematic alcohol consumption in adolescents. EMBASE, MEDLINE, and PsycINFO databases were searched from inception to 6 January 2023. Studies were included if they were original, had a prospective design, had a sample size of at least 12, had a follow-up period of at least 1 year, had at least one structural neuroimaging scan before 18 with no prior alcohol use, and had alcohol use as the primary outcome. Studies were excluded if they had animals only and were not in English. Risk of bias was conducted using the CASP tool. RESULTS: Out of 1412 studies identified, 19 studies met the criteria, consisting of 11 gray matter (n = 4040), 5 white matter (n = 319), and 3 assessing both (n = 3608). Neuroanatomical predictors of future problematic drinking in adolescents were reported to be distributed across various brain regions such as the orbitofrontal cortex and paralimbic regions. However, the findings were largely heterogeneous. CONCLUSIONS: This is the first systematic review to map out the existing literature on neuroanatomical predictors of problematic drinking in adolescents. Future research should focus on the aforementioned regions to determine their role in predicting future problematic drinking with more certainty.
Subject(s)
Brain , Gray Matter , Brain/diagnostic imaging , Cerebral Cortex , Alcohol Drinking/epidemiology , Longitudinal StudiesABSTRACT
Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.
Subject(s)
Brain Neoplasms , Glioma , Female , Humans , Pregnancy , Brain Neoplasms/surgery , Wakefulness/physiology , Craniotomy/methods , Glioma/surgery , Anesthesia, GeneralABSTRACT
BACKGROUND: The postgraduate entrance examination can be a milestone for many medical students to advance their careers. An increasing number of students are competing for limited postgraduate offers available, and failure to enter postgraduate studies can have adverse mental health consequences. In this paper, we aim to investigate the mental health status of medical students during the postgraduate application entrance examination and to provide a targeted basis for mental health education and psychological counselling. METHODS: Using the Symptom Checklist-90 scale (SCL-90) questionnaire, the mental health status of 613 students who passed two rounds of the Postgraduate Entrance Examination in 2019 to enroll in Guangzhou Medical University in China was evaluated and followed up for retesting 6 months later. We used SPSS 20.0 statistical software for comparative analysis, including One-Sample T-Test, Independent-Samples T-Test, Paired Samples T-Test and Chi-square Test. RESULTS: Our data showed that 12.10% of students had mental health problems during the postgraduate entrance examination, and it decreased significantly to 4.40% at the 6-month follow-up after the examination period finished (P < 0.01). Somatization was the most significant symptom of the students both during and after the postgraduate entrance examination stages. All SCL-90 factors were scored significantly lower both in and after the postgraduate entrance examination stages than the 2008 national college student norm score (P < 0.01). Excluding psychiatric factors, all other SCL-90 factors in the postgraduate entrance examination stage scored higher than the graduate stage (P < 0.05), and the total score of SCL-90 in female medical students was higher compared to male students (P < 0.05). CONCLUSION: The postgraduate entrance examination event has a significant negative influence on students' mental health. The mental health of college and graduate students as an important part of their higher education experience should be systematically studied, and psychological counselling or help should be provided to them throughout their studies, specifically during the examination period. Educating applicants about mental health should be implemented during the postgraduate entrance examination curriculum.
Subject(s)
Students, Medical , Humans , Male , Female , Students, Medical/psychology , Mental Health , Curriculum , Surveys and Questionnaires , Health StatusABSTRACT
Augmented and virtual reality (AR, VR) are becoming promising tools in neurosurgery. AR and VR can reduce challenges associated with conventional approaches via the simulation and mimicry of specific environments of choice for surgeons. Awake craniotomy (AC) enables the resection of lesions from eloquent brain areas while monitoring higher cortical and subcortical functions. Evidence suggests that both surgeons and patients benefit from the various applications of AR and VR in AC. This paper investigates the application of AR and VR in AC and assesses its prospective utility in neurosurgery. A systematic review of the literature was performed using PubMed, Scopus, and Web of Science databases in accordance with the PRISMA guidelines. Our search results yielded 220 articles. A total of six articles consisting of 118 patients have been included in this review. VR was used in four papers, and the other two used AR. Tumour was the most common pathology in 108 patients, followed by vascular lesions in eight patients. VR was used for intraoperative mapping of language, vision, and social cognition, while AR was incorporated in preoperative training of white matter dissection and intraoperative visualisation and navigation. Overall, patients and surgeons were satisfied with the applications of AR and VR in their cases. AR and VR can be safely incorporated during AC to supplement, augment, or even replace conventional approaches in neurosurgery. Future investigations are required to assess the feasibility of AR and VR in various phases of AC.
Subject(s)
Augmented Reality , Virtual Reality , Humans , Wakefulness , Craniotomy , Neurosurgical Procedures/methodsABSTRACT
INTRODUCTION: The aim of this study was to investigate for possible associations between an early increase in body temperature within 24 hours of endovascular therapy (EVT) for large vessel occlusion stroke and the presence of symptomatic intracranial hemorrhage (sICH) and other clinical outcomes. METHODS: This was a retrospective study of consecutive patients with large vessel occlusion stroke who were treated with EVT from August 2018 to June 2021. Patients were divided into two groups based on the presence of fever, as defined by a Peak Body Temperature (PBT) of ≥37.3 °C. The presence of sICH and other clinical outcomes were compared between the two groups. RESULTS: The median NIHSS admission score (IQR) was 16.0 (12.0, 21.0), with higher NIHSS scores in the PBT ≥37.3 °C group than in the PBT <37.3 °C group (18 vs 14, respectively; p = 0.002). There were no differences in clinical outcomes at 3 months between patients with PBT <37.3 °C and patients with PBT between 37.3 °C and 38 °C. However, patients with PBT ≥38 °C had an increased risk of sICH (adjusted odds ratio (OR) = 8.8, 95% confidence interval (95% CI): 1.7-46.0; p = 0.01), increased inpatient death or hospice discharge (OR = 10.5, 95% CI: 2.0-53.9; p = 0.005), poorer clinical outcome (OR = 25.6, 95% CI: 5.2-126.8; p < 0.001), and increased 3-month mortality (OR = 6.6, 95% CI: 1.8-24.6; p = 0.01). CONCLUSIONS: Elevated PBT (≥38 °C) within 24 hours of EVT was significantly associated with an increased incidence of symptomatic intracranial hemorrhage, discharge to hospice or inpatient death, poorer clinical outcome and 3-month mortality, and with less functional independence. Further large-scale, prospective and multicenter trials are needed to confirm these findings.
Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Brain Ischemia/complications , Stroke/therapy , Retrospective Studies , Body Temperature , Prospective Studies , Endovascular Procedures/adverse effects , Treatment Outcome , Intracranial Hemorrhages/etiologyABSTRACT
OBJECTIVE: We aimed to evaluate door-to-puncture time (DPT) and door-to-recanalization time (DRT) without directing healthcare by neuro-interventionalist support in the emergency department (ED) by workflow optimization and improving patients' outcomes. METHODS: Records of 98 consecutive ischemic stroke patients who had undergone endovascular therapy (EVT) between 2018 to 2021 were retrospectively reviewed in a single-center study. Patients were divided into three groups: pre-intervention (2018-2019), interim-intervention (2020), and post-intervention (January 1st 2021 to August 16th, 2021). We compared door-to-puncture time, door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), last known normal time to-puncture time (LKNPT), and patient outcomes (measured by 3 months modified Rankin Scale) between three groups using descriptive statistics. RESULTS: Our findings indicate that process optimization measures could shorten DPT, DRT, PRT, and LKNPT. Median LKNPT was shortened by 70 min from 325 to 255 min(P < 0.05), and DPT was shortened by 119 min from 237 to 118 min. DRT shortened by 132 min from 338 to 206 min, and PRT shortened by 33 min from 92 to 59 min from the pre-intervention to post-intervention groups (all P < 0.05). Only 21.4% of patients had a favorable outcome in the pre-intervention group as compared to 55.6% in the interventional group (P= 0.026). CONCLUSION: This study demonstrated that multidisciplinary cooperation was associated with shortened DPT, DRT, PRT, and LKNPT despite challenges posed to the healthcare system such as the COVID-19 pandemic. These practice paradigms may be transported to other stroke centers and healthcare providers to improve endovascular time metrics and patient outcomes.
Subject(s)
COVID-19 , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/surgery , Pandemics , Punctures , Retrospective Studies , Stroke/therapy , Thrombectomy , Time-to-Treatment , Treatment Outcome , WorkflowABSTRACT
OBJECTIVES: This study aims to evaluate shortening door-to-needle time of intravenous recombinant tissue plasminogen activator of acute ischemic stroke patients by multidisciplinary collaboration and workflow optimization based on our hospital resources. MATERIALS AND METHODS: We included patients undergoing thrombolysis with intravenous recombinant tissue plasminogen activator from January 1, 2018, to September 30, 2020. Patients were divided into pre- (January 1, 2018, to December 31, 2019) and post-intervention groups (January 1, 2020, to September 31, 2020). We conducted multi-department collaboration and process optimization by implementing 16 different measures in prehospital, in-hospital, and post-acute feedback stages for acute ischemic stroke patients treated with intravenous thrombolysis. A comparison of outcomes between both groups was analyzed. RESULTS: Two hundred and sixty-three patients received intravenous recombinant tissue plasminogen activator in our hospital during the study period, with 128 and 135 patients receiving treatment in the pre-intervention and post-intervention groups, respectively. The median (interquartile range) door-to-needle time decreased significantly from 57.0 (45.3-77.8) min to 37.0 (29.0-49.0) min. Door-to-needle time was shortened to 32 min in the post-intervention period in the 3rd quarter of 2020. The door-to-needle times at the metrics of ≤ 30 min, ≤ 45 min, ≤ 60 min improved considerably, and the DNT> 60 min metric exhibited a significant reduction. CONCLUSIONS: A multidisciplinary collaboration and continuous process optimization can result in overall shortened door-to-needle despite the challenges incurred by the COVID-19 pandemic.
Subject(s)
Brain Ischemia/drug therapy , COVID-19/complications , Cooperative Behavior , Ischemic Stroke/drug therapy , Patient Care Team , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Early Medical Intervention , Emergency Medical Services , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Pandemics , SARS-CoV-2 , Time Management , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , WorkflowABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the cardinal importance of rapid and accurate diagnostic assays. Since the early days of the outbreak, researchers with different scientific backgrounds across the globe have tried to fulfill the urgent need for such assays, with many assays having been approved and with others still undergoing clinical validation. Molecular diagnostic assays are a major group of tests used to diagnose COVID-19. Currently, the detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) is the most widely used method. Other diagnostic molecular methods, including CRISPR-based assays, isothermal nucleic acid amplification methods, digital PCR, microarray assays, and next generation sequencing (NGS), are promising alternatives. In this review, we summarize the technical and clinical applications of the different COVID-19 molecular diagnostic assays and suggest directions for the implementation of such technologies in future infectious disease outbreaks.
Subject(s)
COVID-19/diagnosis , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , SARS-CoV-2/isolation & purification , COVID-19 Testing/methods , HumansABSTRACT
Traumatic brain injury is a common and major cause of disability and death that might require emergency neurological and neurosurgical interventions. Traumatic brain injury can result in temporary or permanent physical, cognitive and psychological impairments. One of the most common complications associated with traumatic brain injury is post-traumatic headache, associated with significant disability and reduced quality of life. Post-traumatic headache is a public health concern that can affect the long-term outcome of traumatic brain injury patients. Clinical symptoms of post-traumatic headache significantly overlap with common primary headaches such as migraine and tension-type headaches. Beyond neurobiological factors, psychological factors can play crucial roles in the initiation and sustainment of post-traumatic headache. While neurological mechanisms underlying post-traumatic headache remains unknown, different studies suggest various mechanisms such as physical damages to the cranial nerves and neck structure, hyper-sensitization of the pain modulatory pathway, and inflammation as underlying causes for the neurobiology of headache. I explore the hypothesis that traumatic brain injury is associated with headaches. In particular, I provide an overview of the neurobiology of post-traumatic headache, its diagnosis, presenting recent findings on the etiology, explaining similarities and differences between with primary headaches such as migraine and tension-type headache, discuss pharmacological and non-pharmacological interventions for the treatments, as well as emphasising on the psychological importance of post-traumatic headache.
Subject(s)
Brain Injuries, Traumatic , Migraine Disorders , Post-Traumatic Headache , Tension-Type Headache , Brain Injuries, Traumatic/complications , Humans , Migraine Disorders/physiopathology , Post-Traumatic Headache/etiology , Post-Traumatic Headache/physiopathology , Post-Traumatic Headache/therapy , Tension-Type Headache/physiopathologyABSTRACT
BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in TYMP gene, encoding nuclear thymidine phosphorylase (TP). MNGIE mainly presents with gastrointestinal symptoms and is mostly misdiagnosed in many patients as malabsorption syndrome, inflammatory bowel disease, anorexia nervosa, and intestinal pseudo-obstruction. Up to date, more than 80 pathogenic and likely pathogenic mutations associated with the disease have been reported in patients from a wide range of ethnicities. The objective of this study was to investigate the underlying genetic abnormalities in a 25-year-old woman affected with MNGIE. CASE PRESENTATION: The patient was a 25-year-old female referred to our center with the chief complaint of severe abdominal pain and diarrhea for 2 years that had worsened from 2 months prior to admission. The clinical and para-clinical findings were in favor of mitochondrial neurogastrointestinal encephalomyopathy syndrome. Subsequent genetic studies revealed a novel, private, homozygous nonsense mutation in TYMP gene (c. 1013 C > A, p.S338X). Sanger sequencing confirmed the new mutation in the proband. Multiple sequence alignment showed high conservation of amino acids of this protein across different species. CONCLUSION: The detected new nonsense mutation in the TYMP gene would be very important for genetic counseling and subsequent early diagnosis and initiation of proper therapy. This novel pathogenic variant would help us establish future genotype-phenotype correlations and identify different pathways related to this disorder.
Subject(s)
Gastrointestinal Diseases/genetics , Mitochondrial Encephalomyopathies/genetics , Thymidine Phosphorylase/genetics , Abdominal Pain/genetics , Adult , Codon, Nonsense/genetics , Diarrhea/genetics , Female , HumansABSTRACT
BACKGROUND: Environmental uncertainty, such as food deprivation, may alter internal milieu of nervous system through various mechanisms. In combination with circumstances of stress or aging, high consumption of unsaturated fatty acids and oxygen can make neural tissues sensitive to oxidative stress (OS). For adult rats, diminished level of gonadal steroid hormones accelerates OS and may result in special behavioral manifestations. This study was aimed to partially answer the question whether OS mediates trade-off between food hoarding and food intake (fat hoarding) in environmental uncertainty (e.g., fluctuations in food resource) within gonadectomized mouse model in the presence of food deprivation-induced food hoarding behavior. RESULTS: Hoarding behavior was not uniformly expressed in all male mice that exposed to food deprivation. Extended phenotypes including hoarder and non-hoarder mice stored higher and lower amounts of food respectively as compared to that of low-hoarder mice (normal phenotype) after food deprivation. Results showed that neural oxidative status was not changed in the presence of hoarding behavior in gonadectomized mice regardless of tissue type, however, glutathione levels of brain tissues were increased in the presence of hoarding behavior. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde in brain tissues of gonadectomized mice were also seen. CONCLUSIONS: Although, food deprivation-induced hoarding behavior is a strategic response to food shortage in mice, it did not induce the same amount of hoarding across all colony mates. Hoarding behavior, in this case, is a response to the environmental uncertainty of food shortage, therefore is not an abnormal behavior. Hoarding behavior induced neural OS with regard to an increase in brain glutathione levels but failed to show other markers of neural OS. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde levels in brain tissues of gonadectomized mice could be a hallmark of debilitated antioxidative defense and more lipid peroxidation due to reduced amount of gonadal steroid hormones during aging.
Subject(s)
Brain/metabolism , Feeding Behavior/physiology , Food Deprivation/physiology , Hoarding/metabolism , Oxidative Stress/physiology , Spinal Cord/metabolism , Animals , Antioxidants/metabolism , Castration , Disease Models, Animal , Eating/physiology , Feeding Behavior/psychology , Glutathione/metabolism , Lipid Peroxidation/physiology , Male , Malondialdehyde/metabolism , Mice , Random Allocation , Superoxide Dismutase/metabolism , UncertaintyABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a global impact. The past few decades have witnessed significant strides in comprehending the underlying pathophysiological mechanisms and developing diagnostic methodologies for AD, such as neuroimaging approaches. Neuroimaging techniques, including positron emission tomography and magnetic resonance imaging, have revolutionized the field by providing valuable insights into the structural and functional alterations in the brains of individuals with AD. These imaging modalities enable the detection of early biomarkers such as amyloid-ß plaques and tau protein tangles, facilitating early and precise diagnosis. Furthermore, the emerging technologies encompassing blood-based biomarkers and neurochemical profiling exhibit promising results in the identification of specific molecular signatures for AD. The integration of machine learning algorithms and artificial intelligence has enhanced the predictive capacity of these diagnostic tools when analyzing complex datasets. In this review article, we will highlight not only some of the most used diagnostic imaging approaches in neurodegeneration research but focus much more on new tools like artificial intelligence, emphasizing their application in the realm of AD. These advancements hold immense potential for early detection and intervention, thereby paving the way for personalized therapeutic strategies and ultimately augmenting the quality of life for individuals affected by AD.
Subject(s)
Alzheimer Disease , Artificial Intelligence , Early Diagnosis , Neuroimaging , Humans , Alzheimer Disease/diagnostic imaging , Neuroimaging/methods , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Biomarkers/analysisABSTRACT
As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.
ABSTRACT
Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.
ABSTRACT
BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) has emerged as the standard for treating patients with acute ischemic stroke due to large vessel occlusion. The aim of this study was to investigate the relationship between early petechial hemorrhage and patient outcomes after successful EVT of anterior circulation. METHODS: We retrospectively analyzed multicenter data from 316 patients who underwent EVT for acute occlusion of anterior circulation. Patients were divided into petechial hemorrhage group and without hemorrhage group based on post-EVT head imaging. Logistical regression analysis was performed to determine independent predictors for petechial hemorrhage, and for petechial hemorrhage as a predictor of early neurological improvement, favorable outcome at 90 days (modified Rankin Scale 0-2), and 90-day mortality, with adjustment for all factors significantly associated with these endpoints in univariate regression to P < .10. RESULTS: Of 316 included patients with successful EVT, 49 (15.50%) had petechial hemorrhage. The petechial hemorrhage group showed less early neurological improvement (36.73% compared with 53.56%, P = .030), less favorable outcomes at 90 days (32.65% compared with 61.80%, P < .001, absolute risk difference 29.15%), and higher mortality at 90 days (28.57% compared with 10.49%, P = .001) then the group without hemorrhage. Petechial hemorrhage was inversely associated with favorable 90-day outcome (odds ratio = 0.415, 95% CI 0.206-0.835) and higher mortality rate at 90 days (odds ratio = 2.537, 95% CI 1.142-5.635) in multivariable regression but was not independently associated with early neurological improvement. CONCLUSION: In patients with anterior large vessel occlusion who underwent successful EVT, petechial hemorrhage was associated with poor functional outcome and 90-day mortality when adjusted for complete recanalization, pre-EVT National Institute of Health Stroke Scale/Score, and Alberta Stroke Program Early Computed Tomography Score. Despite the relatively lower rate of a favorable 90-day outcome with petechial hemorrhage compared with no petechial hemorrhage, the absolute rate of a favorable outcome exceeds the natural history of medical management for this condition.