Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

Objective: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion.

Mapping neurodegeneration across the Huntington's disease spectrum: a five-year longitudinal analysis of plasma neurofilament light.

Background: Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage.

Methods: 108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study.

Discovery of Alpha-1-Antichymotrypsin as a Marker of Delayed Recovery from Concussion in Children.

Of the four million children who experience a concussion each year, 30-50% of children will experience delayed recovery, where they will continue to experience symptoms more than two weeks after their injury. Delayed recovery from concussion encompasses emotional, behavioral, physical, and cognitive symptoms, and as such, there is an increased focus on developing an objective tool to determine risk of delayed recovery. This study aimed to identify a blood protein signature predictive of delayed recovery from concussion in children.

Capillary blood protein markers of posttraumatic headache in children after concussion.

Objective: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury.

Methods: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion.

Exploring bradyphrenia in Huntington's disease using the computerized test of information processing (CTiP).

Background: Bradyphrenia, best thought of as the mental equivalent of bradykinesia, has been described in several disorders of the brain including Parkinson's disease and schizophrenia; however, little is known about this phenomenon in Huntington's Disease (HD).

Objective: The aim of this study was to investigate the presence of bradyphrenia in HD using the Computerized Test of Information Processing (CTiP), an easy to administer and objective task that assesses cognitive processing speed with increasing task complexity.

Methods: This study included 211 participants: Huntington's Disease Integrated Staging System (HD-ISS) Stage 0 [n = 28], Stage 1 [n = 30], Stage 2 [n = 48] and Stage 3 [n = 48], and healthy controls (HC) [n = 57].

Plasma NfL as a prognostic biomarker for enriching HD-ISS stage 1 categorisation: a cross-sectional study.

Background: The recently proposed Huntington's Disease Integrated Staging System (HD-ISS) categorises individuals with the Huntintin genetic mutation into disease progression cohorts based on quantitative neuroimaging, cognitive, and functional markers for research purposes. Unfortunately, many research studies do not collect quantitative neuroimaging data, and so the authors of the HD-ISS have subsequently provided approximated cohort thresholds based on disease and clinical data alone. However, these are rough proxies that aim to maximise stage separation, and should not be considered as 1:1 substitutes for the HD-ISS.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

Objective: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion.

Rapid Detection of Lithium Concentrations in Oral Fluid.

Background: Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels.

Salivary Huntingtin protein is uniquely associated with clinical features of Huntington's disease.

Measuring Huntingtin (HTT) protein in peripheral cells represents an essential step in biomarker discovery for Huntington's Disease (HD), however to date, investigations into the salivary expression of HTT has been lacking. In the current study, we quantified total HTT (tHTT) and mutant HTT (mHTT) protein in matched blood and saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 (tHTT) and 2B7-MW1 (mHTT). Matched samples, and clinical data, were collected from 95 subjects: n = 19 manifest HD, n = 34 premanifest HD (PM), and n = 42 normal controls (NC).

Associations between saliva and plasma cytokines in cognitively normal, older adults.

Background: Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, especially in elderly populations.

Methods: In this study, we measured levels of 10 cytokines, and the pro-inflammatory factor, YKL-40, in plasma and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; 70.

Provider Perspectives on the Current Use of Lithium Medications and Lithium Monitoring Practices for Psychiatric Conditions.

Purpose: Despite lithium being a gold standard treatment for bipolar disorder, the percentage of patients with bipolar disorder who are prescribed lithium medication has declined in many parts of the world over the past two decades. The use of lithium is limited by its narrow therapeutic window and adverse side effects, which necessitates frequent serum lithium monitoring; hence, there is a critical need for improved ways to monitor lithium levels in psychiatric patients. We have recently shown that saliva lithium levels are highly correlated with those in blood, thereby presenting an alternative to venipuncture.

Catalytic reduction of carbon dioxide by a zinc hydride compound, [Tptm]ZnH, and conversion to the methanol level.

The zinc hydride compound, [Tptm]ZnH, may achieve the reduction of CO by (RO)SiH (R = Me, Et) to the methanol oxidation level, (MeO)Si(OR), the formate species, HCOSi(OR). However, because insertion of CO into the Zn-H bond is more facile than insertion of HCOSi(OR), conversion of HCOSi(OR) to the methanol level only occurs to a significant extent in the absence of CO.

Leveling the Playing Field: A New Proposed Method to Address Relative Age- and Maturity-Related Bias in UK Male Academy Soccer Players.

Relative age selection bias persists within all major soccer leagues and youth soccer academies across the globe, with the relative age effect (RAE) being typically characterized as the over selection of relatively older players (who have sometimes also been shown to be early maturing). The aim of this study was to examine if a new allocation method (i) eliminates the RAE, and (ii) reduces the presence of any additional maturity-related differences in anthropometric and physical fitness characteristics which may exist between players within the same selection category. In the first phase, 1,003 academy soccer players [under (U) 9-16] from 23 UK professional soccer clubs were sampled and a clear RAE per birth quarter (Q) was observed for the overall sample (Q1 = 45.

Associations between prognostic index scores and plasma neurofilament light in Huntington's disease.

Introduction: The inclusion of premanifest Huntington's Disease (Pre-HD) subjects in clinical trials necessitates selecting those who are near transition to manifest Huntington's disease (Man-HD). We previously determined that plasma neurofilament light (NfL) levels are significantly correlated with predicted years to Man-HD onset, using established formulae. Recently, a new normalized prognostic index (PIN) score for predicting Pre-HD disease progression has been validated.

Synthesis of bis(2-pyridylthio)methyl zinc hydride and catalytic hydrosilylation and hydroboration of CO.

The reactions of bis(2-pyridylthio)methane with MeZn and Zn[N(SiMe)] afford [Bptm]ZnMe and [Bptm]ZnN(SiMe), thereby providing access to a variety of other [Bptm]ZnX derivatives, including the zinc hydride complex [Bptm]ZnH, which serves as a catalyst for the reduction of CO and other carbonyl compounds hydrosilylation and hydroboration.

Impact of the coordination of multiple Lewis acid functions on the electronic structure and v configuration of a metal center.

The covalent bond classification (CBC) method represents a molecule as MLXZ by evaluating the total number of L, X and Z functions interacting with M. The CBC method is a simplistic approach that is based on the notion that the bonding of a ligating atom (or group of atoms) can be expressed in terms of the number of electrons it contributes to a 2-electron bond. In many cases, the bonding in a molecule of interest can be described in terms of a 2-center 2-electron bonding model and the MLXZ classification can be derived straightforwardly by considering each ligand independently.

The effect of bio-banding on the anthropometric, physical fitness and functional movement characteristics of academy soccer players.

The study examined if maturity status bio-banding reduces within-group variance in anthropometric, physical fitness and functional movement characteristics of 319, under-14 and under-15 players from 19 UK professional soccer academies. Bio-banding reduced the within-bio-banded group variance for anthropometric values, when compared to an aggregated chronological banded group (chronological: 5.1-16.

Saliva testing as a means to monitor therapeutic lithium levels in patients with psychiatric disorders: Identification of clinical and environmental covariates, and their incorporation into a prediction model.

Objective: The narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitudinal salivary lithium level monitoring.

Accuracy of Components of the SCAT5 and ChildSCAT5 to Identify Children with Concussion.

The Sport Concussion Assessment Tool 5 Edition (SCAT5) is a standardized measure of concussion. In this prospective observational study, the ability of the SCAT5 and ChildSCAT5 to differentiate between children with and without a concussion was examined. Concussed children (n=91) and controls (n=106) were recruited from an emergency department in three equal-sized age bands (5-8/9-12/13-16 years).

Synthesis, Structure, and Reactivity of a Terminal Cadmium Hydride Compound, [κ-Tism]CdH.

The terminal cadmium hydride compound, [κ-Tism]CdH, which features the tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl ligand, may be obtained the reactions of either [κ-Tism]CdN(SiMe) or [Tism]CdOSiPh with PhSiH. The Cd-H bond of [κ-Tism]CdH undergoes (a) metathesis reactions with MeI, MeSiX (X = Cl, Br, I, NCO), and MeSnX (X = Cl, Br, I) to afford the corresponding [Tism]CdX derivative, (b) insertion with CO and CS to afford respectively [Tism]Cd(κ-OCH) and [Tism]Cd(κ-SCH), and (c) hydride abstraction with B(CF) to afford {[Tism]Cd}[HB(CF)] that possesses a rare trigonal monopyramidal geometry for cadmium.

Rhenium cadmium: an alternative structure for a thermally stable cadmium carbonyl compound.

An alternative description is provided for the previously reported novel tetranuclear cadmium carbonyl compound, [Cd(CO)(CHCl)]. Specifically, consideration of single crystal X-ray diffraction data indicates that the compound is better formulated as the rhenium compound, [Re(CO)(CNHS)]. Furthermore, density functional theory calculations predict that, if it were to exist, [Cd(CO)(CHCl)] would have a very different structure to that reported.

Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.

Objective: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy.

Method: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated.

Validation of the SCAT5 and Child SCAT5 Word-List Memory Task.

The Sports Concussion Assessment Tool-5th Edition (SCAT5) and the child version (Child SCAT5) are the current editions of the SCAT and have updated the memory testing component from previous editions. This study aimed to validate this new memory component against the Rey Auditory Verbal Learning Test (RAVLT) as the validated standard. This prospective, observational study, carried out within The Royal Children's Hospital Emergency Department, Melbourne, Australia, recruited 198 participants: 91 with concussion and 107 upper limb injury or healthy sibling controls.