99mTc‐(EDDA/tricine)‐HYNIC‐GnRH analogue as a potential imaging probe for diagnosis of prostate cancer

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by ^99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The K_d values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of ^99mTc‐HYNIC‐Ahx‐[DLys⁶]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using ^99mTc‐[DLys⁶]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.     

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item “short” to 65-item “full” SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.

     

Stroke as a Neurological Complication of COVID-19: A Systematic Review and Meta-Analysis of Incidence,Outcomes and Predictors

IntroductionCOVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis. The consequences of this include renal dysfunction, hepatitis and stroke. In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19.MethodsWe conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19.Results326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included. The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4–76.4 years). The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%). The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%). These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts.ConclusionAlthough stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality. In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.     

Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study

Journal of Neurology - Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not...     

Dynamic functional connectivity in temporal lobe epilepsy: a graph theoretical and machine learning approach

Purpose

Functional magnetic resonance imaging (fMRI) in resting state can be used to evaluate the functional organization of the human brain in the absence of any task or stimulus. The functional connectivity (FC) has non-stationary nature and consented to be varying over time. By considering the dynamic characteristics of the FC and using graph theoretical analysis and a machine learning approach, we aim to identify the laterality in cases of temporal lobe epilepsy (TLE).

Methods

Six global graph measures are extracted from static and dynamic functional connectivity matrices using fMRI data of 35 unilateral TLE subjects. Alterations in the time trend of the graph measures are quantified. The random forest (RF) method is used for the determination of feature importance and selection of dynamic graph features including mean, variance, skewness, kurtosis, and Shannon entropy. The selected features are used in the support vector machine (SVM) classifier to identify the left and right epileptogenic sides in patients with TLE.

Results

Our results for the performance of SVM demonstrate that the utility of dynamic features improves the classification outcome in terms of accuracy (88.5% for dynamic features compared with 82% for static features). Selecting the best dynamic features also elevates the accuracy to 91.5%.

Conclusion

Accounting for the non-stationary characteristics of functional connectivity, dynamic connectivity analysis of graph measures along with machine learning approach can identify the temporal trend of some specific network features. These network features may be used as potential imaging markers in determining the epileptogenic hemisphere in patients with TLE.

     

MR Imaging–Detected Carotid Plaque Hemorrhage Is Stable for 2 Years and a Marker for Stenosis Progression

BACKGROUND AND PURPOSE:MR imaging–detected carotid plaque hemorrhage is associated with an increased risk of recurrent ischemic cerebrovascular events and could be an indicator of disease progression; however, there are limited data regarding the dynamics of the MR imaging–detected carotid plaque hemorrhage signal. We assessed the temporal change of this signal and its impact on carotid disease progression.MATERIALS AND METHODS:Thirty-seven symptomatic patients with 54 carotid stenoses of >30% on sonography underwent serial MR imaging during 24 months. A signal-intensity ratio of >1.5 between the carotid plaque and adjacent muscle was defined as plaque hemorrhage, and a change in signal-intensity ratio of >0.31 between time points was considered significant. Sixteen patients underwent ≥2 carotid sonography scans to determine the peak systolic velocities and degree of stenosis with time.RESULTS:Of the 54 carotids, 28 had the presence of hyperintense signal on an MR imaging sequence (PH+) and 26 had the absence of hyperintense signal on an MR imaging sequence (PH−) at baseline. The signal-intensity ratio was stable in 33/54 carotid plaques, but 39% showed a change. Plaque hemorrhage classification did not change in 87% of carotid plaques, but 4 became PH+, and 3, PH−. As a group, PH+ carotids did not change significantly in signal-intensity ratio (P = .585), whereas PH− showed an increased signal-intensity ratio at 24.5 months (P = .02). In PH+ plaques, peak systolic velocities significantly increased by 22 ± 39.8 cm/s from baseline to last follow-up sonography (Z = 2.427, P = .013).CONCLUSIONS:During 2 years, MR imaging–detected carotid plaque hemorrhage status remained stable in most (87%) cases with 4 (7%) incident plaque hemorrhages. PH+ plaques were associated with increased flow velocity during the follow-up period.

Currently, the degree of ICA stenosis is the principal criterion on the basis of which the decision for carotid intervention is made. This is based on strong evidence from randomized controlled trials that carotid endarterectomy reduces stroke risk in patients with severe carotid artery stenosis.^1,2 However, those studies also showed that a significant proportion of patients with symptomatic carotid disease will not have a recurrence. Subsequently, much research is focused on the identification of high-risk subgroups,³ especially for those with moderate or asymptomatic carotid stenosis.Plaque hemorrhage (PH) is implicated in carotid plaque vulnerability⁴ and is detectable by MR imaging.^5,6 A recent longitudinal follow-up study and meta-analysis⁷ demonstrated that MR imaging–detected plaque hemorrhage (MR imaging-PH) strongly predicts recurrent ischemic events. The MR imaging-PH signal seems to be stable for 12 months,⁸ but stability of MR imaging-PH features beyond 12 months remains unclear. Knowledge of longer term stability of MR imaging-PH would be helpful if it is to be used to assist decision-making in interventions and to determine the need for follow-up imaging.Plaque volume progression on sonography recently has been shown to predict cerebrovascular events⁹; however, this measure was not used in the current study. Carotid stenosis progression has been suggested to be a better predictor of subsequent TIA/stroke than a single measurement.¹⁰ Although general carotid sonography surveillance may not be cost-effective,¹¹ this situation may well be different for a subgroup of patients with a higher risk for stenosis progression. It is conceivable that MR imaging-PH is also an indicator of disease progression¹² and, therefore, may be useful in this regard.The aim of this study was to determine MR imaging signal changes in the carotid artery plaque during 2 years and whether the presence of MR imaging-PH at baseline is associated with stenosis progression.     

Differentiation of Wharton's jelly mesenchymal stem cells into neurons in alginate scaffold

Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton's jelly mesenchymal stem cells(WJMSCs) and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin(marker for WJMSCs-differentiated neuron) and CD271(motor neuron marker). β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.     

12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.