Doublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in ...neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers.
CSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays.
From March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years Q1: 0.31, Q3: 7.72. The median concentration of DCX was 329 pg/ml Q1: 192.5, Q3: 1179.6 and that of GPC2 was 26 pg/ml Q1: 13.25, Q3: 149.25. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1β, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively.
Concentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent findings describe microglia as modulators of neurogenesis in the subventricular zone (SVZ). SVZ microglia in the adult rat are thought to adopt a neurotrophic phenotype after ischemic stroke. ...Early postnatal microglia are endogenously activated and may therefore exhibit an increased sensitivity to neonatal hypoxia-ischemia (HI). The goal of this study was to investigate the impact of cortico-striatal HI on the microglial phenotype, function, and gene expression in the early postnatal SVZ.
Postnatal day (P)7 rats underwent sham or right-hemispheric HI surgery. Microglia in the SVZ, the uninjured cortex, and corpus callosum were immunohistochemically analyzed at P10, P20, and P40. The transcriptome of microdissected SVZ and cortical microglia was analyzed at P10 and P20, and the effect of P10 SVZ microglia on neurosphere generation in vitro was studied.
The microglial response to HI was region-specific. In the SVZ, a microglial accumulation, prolonged activation and phagocytosis was noted that was not observed in the cortex and corpus callosum. The transcriptome of SVZ microglia and cortical microglia were distinct, and after HI, SVZ microglia concurrently upregulated pro- and anti-inflammatory as well as neurotrophic genes. In vitro, microglia isolated from the SVZ supported neurosphere generation in a concentration-dependent manner.
Microglia are an inherent cellular component of the early postnatal SVZ and undergo developmental changes that are affected on many aspects by neonatal HI injury. Our results demonstrate that early postnatal SVZ microglia are sensitive to HI injury and display a long-lasting region-specific response including neurotrophic features.
ObjectivesWe aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in ...healthcare.MethodsA simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines.ResultsA central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs’ text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance.DiscussionLatest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM’s unique algorithm rather than output length.ConclusionsUsers must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models' comprehension of complex medical scenarios and their ability to provide reliable information.
Abstract
Background
Observational studies have shown that dressings containing chlorhexidine gluconate (CHX) lower the incidence external ventricular drain (EVD)-associated infections (EVDAIs). This ...prospective, randomized controlled trial (RCT) studies the efficacy of CHX-containing dressings in reducing bacterial colonization.
Methods
In this RCT, patients aged ≥18 years undergoing emergency EVD placement were randomly given either a CHX-containing or an otherwise identical control dressing at the skin exit wound. The primary end-point was bacterial regrowth in cultured skin swab samples of the EVD exit wound. The secondary end-points were catheters processed by sonication, clinically diagnosed EVDAI and surgical treatment of hydrocephalus.
Results
From October 2013 to January 2016, a total of 57 patients were randomized to receive either a CHX or a control dressing (29 and 28 patients, respectively). Cutaneous bacterial regrowth at the EVD exit wound was significantly reduced over time (geometric mean ratio, 0.18; 95% confidence interval, .08-.42; P < .001). The incidence of colonized catheters was lower in the CHX group (5 of 28; 18%) than in the control group (10 of 27; 33%), with less microbial colonization on the subcutaneous portion. The infection rate was 4 of 28 (14%) in the CHX group, compared with 7 of 27 (26%) in the control group, with a substantially lower hydrocephalus treatment rate (7 of 28 25% vs 14 of 27 52%, respectively).
Conclusion
Our data support the use of CHX dressings to reduce EVD exit site contamination, potentially reducing EVDAIs and permanent cerebrospinal fluid diversion procedures for hydrocephalus.
Clinical Trials Registration
NCT02078830.
This prospective, randomized controlled trial studies the effectiveness of chlorhexidine-coated dressings in reducing bacterial colonization of external ventricular drains and supports their use to reduce exit site contamination and potentially reduce infections and permanent cerebrospinal fluid diversion procedures for hydrocephalus.
To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs ...post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke.
The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data.
Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median interquartile range) increased significantly post-partum: 49.4 (34.7-77.8) vs 27.7 (16.7-31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age.
Parturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.
Neurofilament light chain (NfL) is a highly promising biomarker of neuroaxonal injury that has mainly been studied in adult neurodegenerative disease. Its involvement in neonatal disease remains ...largely unknown. Our aim was to establish NfL plasma concentrations in preterm and term infants in the first week of life.
Plasma NfL was measured by single molecule array immunoassay in two neonatal cohorts: cohort 1 contained 203 term and preterm infants, median gestational age (GA) 37.9 weeks (interquartile range IQR 31.9-39.4), in whom venous and arterial umbilical cord blood was sampled at birth and venous blood at day of life (DOL) 3; cohort 2 contained 98 preterm infants, median GA 29.3 weeks (IQR 26.9-30.6), in whom venous blood was sampled at DOL 7.
Median NfL concentrations in venous blood increased significantly from birth (18.2 pg/mL IQR 12.8-30.8, cohort 1) to DOL 3 (50.9 pg/mL 41.3-100, cohort 1) and DOL 7 (126 pg/mL 78.8-225, cohort 2) (
< 0.001). In both cohorts NfL correlated inversely with birth weight (BW, Spearman's rho -0.403,
< 0.001, cohort 1; R -0.525,
< 0.001, cohort 2) and GA (R -0.271,
< 0.001, cohort 1; R -0.487,
< 0.001, cohort 2). Additional significant correlations were found for maternal age at delivery, preeclampsia, delivery mode, 5-min Apgar, duration of oxygen supplementation, sepsis, and brain damage (intraventricular hemorrhage or periventricular leukomalacia). Multivariable logistic regression analysis identified the independent predictors of NfL in cohort 1 as BW (beta = -0.297,
= 0.003), delivery mode (beta = 0.237,
= 0.001) and preeclampsia (beta = 0.183,
= 0.022) and in cohort 2 as BW (beta = -0.385,
= 0.001) and brain damage (beta = 0.222,
= 0.015).
Neonatal NfL levels correlate inversely with maturity and BW, increase during the first days of life, and relate to brain injury factors such as intraventricular hemorrhage and periventricular leukomalacia, and also to vaginal delivery.
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