To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline.
...FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.
PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score.
Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.
Following the retirement of the community supported Van Allen Probes mission, the quest for high‐quality energetic particle measurements in the radiation belts is likely to be taken on by smaller ...spacecraft like CubeSats in the foreseeable future. Here we introduce the Relativistic Electron Proton Telescope integrated little experiment‐2 (REPTile‐2), a miniaturized (∼1.5 U) solid‐state charged particle telescope that aims to undertake this challenging task. It incorporates detailed pulse‐height analysis to enable 60 electron channels and 60 proton channels and includes anticoincidence detectors to minimize unwanted background contamination. This paper presents a description of the REPTile‐2 design and emphasizes the importance of extensive Geant4‐based analysis to inform the design of a new energetic particle detector and characterize the instrument response. Our analysis shows that REPTile‐2 can measure ∼0.3–∼4 MeV electrons and ∼6.7–35 MeV protons with energy resolution (∆E/E) of 7%–38% for electrons and 1.5%–5% for protons. Results from a Sr‐90/Y‐90 radioactive source test have verified the instrument performance and the validity of the Geant4 simulations. These energetic particle measurements will enable a new scientific understanding of the inner radiation belt, where unwanted contamination from the unforgiving penetration of highly energetic protons (tens of MeV to GeV) is common, and provide detailed quantification of the inner belt electrons and protons in the low‐Earth orbit that is crucial for space weather modeling.
Key Points
REPTile‐2 is a miniaturized particle telescope measuring electrons and protons with fine energy resolution and minimal contamination
This study highlights the key role of anticoincidence detectors in reducing contamination and improving measurement quality
Detailed Geant4 simulations have proved to be instrumental in characterizing instrument response and potential contamination sources
Translational control at the initiation step has been recognized as a major and important regulatory mechanism of gene expression. Eukaryotic initiation factor-3a (eIF3a), a putative subunit of the ...eIF3 complex, has recently been shown to have an important role in regulating the translation of a subset of mRNAs and is found to correlate with the prognosis of cancers. In this study, using nasopharyngeal carcinoma (NPC) cells as a model system, we tested the hypothesis that eIF3a negatively regulates the synthesis of nucleotide excision repair (NER) proteins, and, in turn, cellular response to treatments with DNA-damaging agents such as cisplatin (cis-dichlorodiammine platinum(II) (CDDP)). We found that a CDDP-sensitive sub-clone S16 isolated through limited dilution from an NPC cell line CNE-2 has increased eIF3a expression. Knocking down its expression in S16 cells increased cellular resistance to CDDP, NER activity and synthesis of the NER proteins XPA, XPC, RAD23B and RPA32. Altering eIF3a expression also changed the cellular response to CDDP and UV treatment in other NPC cell lines. Taken together, we conclude that eIF3a has an important role in the CDDP response and in NER activity of NPCs by suppressing the synthesis of NER proteins.
Abstract
The skin is the largest organ in the body and the skin barrier is important to reduce moisture loss, prevent irritations and bacterial infections. The complex skin barrier consists of ...essential lipids such as ceramides together with cholesterol and free fatty acids. Hydroxypropyl Bispalmitamide MEA or PC-104 is claimed to be a compound created to mimic ceramides and claimed to have similar effectiveness as Ceramide 3 at moisturising the skin and restoring the skin barrier. The objective of this study is to evaluate the structure characterisation of Hydroxypropyl Bispalmitamide MEA and whether it can be categorised as a ceramide. Three different spectroscopy and physico chemical analysis conducted on the two samples revealed the structural formula and chemical composition of Hydroxypropyl Bispalmitamide MEA to be different from Ceramide 3. Therefore, the two compounds cannot be considered to contain the same chemical structural make up, based on spectral analysis generated by instrumentation. Hydroxypropyl Bispalmitamide MEA cannot be categorised as a ceramide because it is lacking the sphingosine moiety.
Nonmotor symptoms (NMS) are common in patients with established Parkinson disease (PD) but their frequency in early PD has not been extensively studied. Our aim was to determine the frequency of NMS ...in a cohort of patients with newly diagnosed PD.
A total of 159 patients with early PD and 99 healthy controls participated in this study. NMS were screened for using the nonmotor symptom questionnaire. Other assessments included measures of motor disability (Movement Disorders Society-revised unified Parkinson's disease rating scale MDS-UPDRS), disease severity (Hoehn & Yahr staging), depression (geriatric depression scale), and global cognitive function (Mini-mental state examination and Montreal cognitive assessment).
The PD group reported a significantly greater number of NMS compared with controls (8.4 4.3 vs. 2.8 2.6). In the PD group, the most commonly experienced NMS were excessive saliva, forgetfulness, urinary urgency, hyposmia, and constipation. Patients with higher MDS-UPDRS III scores and those with the postural instability gait subtype experienced a greater number of NMS.
NMS are common in early PD and reflect the multisystem nature of the disorder. Even in the earliest stages of PD, NMS may be detrimental to patients' functional status and sense of well-being.
Recent ATLAS data significantly extend the exclusion limits for supersymmetric particles. We examine the impact of such data on global fits of the constrained minimal supersymmetric standard model ...(CMSSM) to indirect and cosmological data. We calculate the likelihood map of the ATLAS search, taking into account systematic errors on the signal and on the background. We validate our calculation against the ATLAS determinaton of 95% confidence level (C.L.) exclusion contours. A previous CMSSM global fit is then re-weighted by the likelihood map, which takes a bite at the high probability density region of the global fit, pushing scalar and gaugino masses up.
Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M‐CaP) Study to investigate the ...clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi‐ethnic Asian men at real‐world setting. The M‐CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow‐up and vital status data were retrieved prospectively from the hospital‐based patients’ case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression‐free survival (bPFS). The median age at diagnosis of M‐CaP patients was 70 years (interquartile range, IQR 65–75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow‐up for all patients was 23.5 months (IQR 15.9–33.6). Although 58.1% presented with late‐stage cancer, we observed ethnic and geographic disparities in late‐stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6–20.8), respectively. Late stage at presentation remains a challenge in multi‐ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer.
Late stage at presentation remains a challenge in multi‐ethnic Asian men. We observed ethnic and geographic disparities in late stage prostate cancer diagnosis. Early detection is imperative to improve treatment outcome and survival of prostate cancer patients.
The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and ...inflammation.
There is an increasing interest among researchers in searching for new anticancer drugs from natural resources, particularly plants. This study aimed to investigate the anticancer properties of Acalypha wilkesiana extracts and the characteristics of DNA damage against brain and lung cancer cells.
The antiproliferative activity of Acalypha wilkesiana extracts (ethyl acetate, hexane, and ethanol) was examined on human glioma (U87MG), human lung carcinoma (A549), and human lung fibroblast (MRC5) cells.
Cell viability MTT assay revealed that ethyl acetate extract of the plant possessed significant antiproliferative effects against both U87MG (GI50=28.03±6.44μg/ml) and A549 (GI50=89.63±2.12μg/ml) cells (p value<0.0001). The hexane extract was found to exhibit crucial antiproliferative effects on U87MG (GI50=166.30±30.50μg/ml) (p value<0.0001) but not on A549 cells. Neither plant extract possessed noticeable antiproliferative effects on the non-cancerous MRC5 cells (GI50>300μg/ml). The ethanol extract showed no antiproliferative effects on any cell line examined. Haematoxylin & Eosin (H & E) staining and single cell gel electrophoresis (SCGE) comet assay confirmed that plant extract-treated cells underwent apoptosis and not necrosis. SCGE comet assays confirmed that plant extracts caused both single strand (SSB) and double strand (DSB) DNA breaks that led to the execution of apoptosis.
The extracts (especially ethyl acetate and hexane) of Acalypha wilkesiana possess valuable cytotoxic effects that trigger apoptosis in U87MG and A549 cancer cells through induction of DNA SSBs and DSBs.
A distinct feature of the tumor vasculature is its tortuosity and irregular branching of vessels, which can translate to a wider dispersion and higher variability of blood flow in the tumor. To ...enable tumor blood flow variability to be assessed in vivo by imaging, a tracer kinetic model that accounts for flow dispersion is developed for use with dynamic contrast-enhanced (DCE) CT. The proposed model adopts a multiple-pathway approach and allows for the quantification of relative dispersion in the blood flow distribution, which reflects flow variability in the tumor vasculature. Monte Carlo simulation experiments were performed to study the possibility of reducing the number of model parameters based on the Akaike information criterion approach and to explore possible noise and tissue conditions in which the model might be applicable. The model was used for region-of-interest analysis and to generate perfusion parameter maps for three patient DCE CT cases with cerebral tumors, to illustrate clinical applicability.
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