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Πέμπτη 26 Νοεμβρίου 2020

DWI cerebellar infarct volume as predictor of outcomes after endovascular treatment of acute basilar artery occlusion

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Background

Preprocedural predictors of outcome in patients with acute basilar artery occlusion (ABAO) who have undergone endovascular treatment (EVT) remain controversial. Our aim was to determine if pre-EVT diffusion-weighted imaging cerebellar infarct volume (CIV) is a predictor of 90-day outcomes.

Methods

We analyzed consecutive MRI-selected endovascularly treated patients with ABAO within the first 24 hours after symptom onset. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infa rction score of 2b–3. Using the initial MRI, baseline CIV was calculated in mL on an apparent diffusion coefficient map reconstruction (Olea Sphere software). CIV was analyzed in univariate and multivariable models as a predictor of 90-day functional independence (modified Rankin Scale (mRS) 0–2) and mortality. According to receiver operating characteristic (ROC) analysis, the optimal cut-off was determined by maximizing the Youden index to evaluate the prognostic value of CIV.

Results

Of the 110 MRI-selected patients with ABAO, 64 (58.18%) had a cerebellar infarct. The median CIV was 9.6 mL (IQR 2.7–31.4). Successful reperfusion was achieved in 81.8% of the cases. At 90 days the proportion of patients with mRS ≤2 was 31.8% and the overall mortality rate was 40.9%. Baseline CIV was significantly associated with 90-day mRS 0–2 (p=0.008) in the univariate analysis and was an independent predictor of 90-day mortality (adjusted OR 1.79, 95% CI 1.25 to 2.54, p=0.001). The ROC analysis showed that a CIV ≥4.7 mL at the initial MRI was the optimal cut-off to discriminate patients with a higher risk of death at 90 days (area under the ROC curve (AUC)=0.74, 95% CI 0.61 to 0.87, sensitivity and specificity of 87.9% and 58.1%, respectively).

Conclusions

In our series of MRI-selected patients with ABAO, pre-EVT CIV was an independent predictor of 90-day mortality. The risk of death was increased for baseline CIV ≥4.7 mL.

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Multiple cranial nerve enlargement in Charcot-Marie-Tooth disease

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Hypertrophy of peripheral nerves are commonly reported in patients with demyelinating forms of Charcot-Marie-Tooth disease (CMT).1 Herein, an under-recognised association with hypertrophy of multiple cranial nerves in a patient with CMT is described.

A 39-year-old otherwise healthy man presented with a 2-month history of tension-type headaches without other associated neurological symptoms. Examination showed normal visual acuity but mild blunting of the nasal disc margins bilaterally on funduscopy. No other crani al nerve abnormalities were elicited. In the lower limbs, there was prominent pes cavus deformity involving both feet (figure 1A) associated with subtle ankle dorsiflexion weakness and impaired distal proprioception. Power in the upper limbs was normal and deep tendon reflexes were globally depressed.

Neurophysiological examination () revealed absent sensory responses in the upper and lower limbs while distal motor responses in the lower limbs were reduced in amplitude. Distal motor latencies were significantly prolonged in the upper and...

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Impact of oral textures on aspiration and changes in swallow dynamics in patients with PD with DBS

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Introduction

Aspiration secondary to impaired swallow function, or dysphagia, is one of the major causes of mortality in patients with Parkinson's disease (PD). Dysphagia usually does not respond well to medications. Despite its effectiveness on motor fluctuation, dyskinesia and tremor in patients with PD, deep brain stimulation (DBS) is not as effective on axial symptoms of balance, freezing of gait (FOG), speech and swallow function. Studies even raise concerns about axial symptoms under usual high-frequency stimulat ion (HFS) of the subthalamic nucleus (STN), particularly ON medication.1 STN DBS has various effects on swallow function.2–4 Swallowing involves multiple phases, with oral and pharyngeal phases most critical for bolus clearance and airway protection. However, the impact of different oral textures on aspiration with or without DBS in patients with PD has not been studied.2 Fast-flowing liquids may be more likely to aspirate before...

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Blastic Plasmacytoid Dendritic-Cell Neoplasm

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Figure 1.
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Validity of Soprolife camera and Calcivis device in caries lesion activity assessment

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British Dental Journal, Published online: 26 November 2020; doi:10.1038/s41415-020-2316-x

Validity of Soprolife camera and Calcivis device in caries lesion activity assessment
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Sequestration of eIF4A by Angiomotin: a novel mechanism to restrict global protein synthesis in trophoblast cells

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Sequestration of eIF4A by Angiomotin: a novel mechanism to restrict global protein synthesis in trophoblast cells

Schematic representation of AMOT function during differentiation of TSCs. AMOT is expressed by ectoplacental cone on E7.5 during mouse development. EPC harbors TSC niche. Low levels of AMOT in TSCs ensure optimum protein synthesis. Differentiation dependent up regulation of AMOT lead to sequestration of eIF4A and subsequent decrease of eIF4A‐eIF4G interaction and decreased eIF4F complex formation at the m7‐GTP cap resulting in decreased protein synthesis.


Abstract

Enrichment of Angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT‐interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In depth analysis of AMOT‐interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT‐eIF4A binding suggested a strong AMOT‐eIF4A interaction using a distinct groove encompassing amino acid residue positions 238‐255 of AMOT. Co‐immunoprecipitation of AMOT with eIF4A re‐affirmed AMOT‐eIF4A association in trophoblast cells. Deletion of 238‐255 amino acids of AMOT resulted in abrogation of AMOT‐eIF4A interaction. In addition, 238‐255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT dependent sequestration of eIF4A dampened its loading to the m7‐GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intra‐uterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.

© AlphaMed Press 2020

Significance Statement

Trophoblast cells, the parenchymal cells of placenta, execute most placental functions, indispensible for successful pregnancy. They arise from the trophoblast stem cell (TSC) niche during development. TSCs are recognized as the developmental counterpart of ES cells in the context of placental development. Inadequate, trophoblast differentiation leads to adverse pregnancy outcome, which is a global health concern. Expanding the knowledge on the regulatory circuits of trophoblast development is therefore essential to improve the success of pregnancy.

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Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition

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Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition

We generated human induced pluripotent stem cell‐derived alveolar type I (iAT1) cells in alveolar organoids (AOs) and showed that the transcriptomes of iAT1 cells were similar to those of primary AT1 cells. We generated iAT1 cells by inhibiting canonical Wnt signaling and propose AOs as a useful tool for understanding the differentiation of alveolar type II (AT2) cells into AT1 cells.


Abstract

Alveologenesis is a developmental step involving the expansion of the lung surface area which is essential for gas exchange. The gas exchange process is mediated by alveolar type I (AT1) cells, which are known to be differentiated from alveolar type II (AT2) or bipotent cells. Due to the difficulty of isolating and culturing primary AT1 cells, the mechanism underlying their differentiation is not completely understood. We performed single‐cell RNA sequencing (scRNA‐seq) of fibroblast‐dependent alveolar organoids (FD‐AOs), including human induced pluripotent stem cell (hiPSC)‐derived epithelial cells and fetal lung fibroblasts, and identified hiPSC‐derived AT1 (iAT1) cells. A comparison of the FD‐AOs and fibroblast‐free alveolar organoids showed that iAT1 cells were mainly present in the FD‐AOs. Importantly, the transcriptomes of iAT1 cells were remarkably similar to those of primary AT1 cells. Additionally, XAV‐939, a tankyrase inhibitor, increased iAT1 cells i n passaged FD‐AOs, suggesting that these cells were differentiated from hiPSC‐derived AT2 (iAT2) cells through the inhibition of canonical Wnt signaling. Consequently, our scRNA‐seq data allowed us to define iAT1 cells and identify FD‐AOs as a useful model for investigating the mechanism underlying human AT1 cell differentiation from AT2 cells in vitro.

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Osmo- and cryotherapy of sugarcane ( Saccharum spp. L.) shoot-tips infected with sugarcane mosaic virus (SCMV)

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Abstract

In this work, we investigated the effect of different osmoprotective treatments and of cryopreservation using a droplet-vitrification (D-V) protocol to eliminate sugarcane mosaic virus (SCMV) of shoot-tips excised from in vitro propagated infected plantlets. Shoot-tips of sugarcane (Saccharum spp. L.) were precultured on semisolid MS medium supplemented with 0.3 M sucrose for 1 day, loaded in solution with 0.4 M sucrose and 2 M glycerol for 30 min and exposed to plant vitrification solution 2 for 15 min at room temperature prior to ultra-rapid cooling in liquid nitrogen. Virus indexing was performed by the DAS-ELISA immunoenzymatic test. The presence of SCMV was confirmed in the donor-plantlets derived of infected field material. No virus was detected in the regenerated plantlets from shoot-tips subjected to cryopreservation protocol. The progressive decrease in absorbances occurred from the first preculture treatment and no significant differences (P ≤ 0.05) were found with respect to following steps of D-V protocol. These results indicate that the osmotic dehydration treatments (osmotherapy) and cryopreservation (cryotherapy) may be potentially effective strategies to remove the SCMV from infected plants.

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Occurrence of granulovirus infecting Cydia pomonella in high altitude cold

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Abstract

Codling moth (Cydia pomonella, Lepidoptera: Tortricidae) is a quarantine pest of apple in Ladakh, India. We report Cydia pomonella granulovirus from infected larvae of codling moth for the first time in India. The two CpGV isolates were identified as (CpGV SKUAST-1 and CpGV SKUAST-2) and published in Genbank under accession number, MK801791 and MK801792, respectively. The mortality of CpGV was evaluated against 3rd instar larvae of codling moth at various concentrations viz., 102, 104, 106, 108, 1010, 1012 and 1014 OBS/ml. The median lethal concentrations (LC50 and LC90) were observed at 7.08 and 28.56 OBS/ml, respectively. In field, the infection rate by CpGV was 5.95 to 15.65%. Based on typical infection symptoms on the larvae, morphological features under the microscope and sequence results of the amplified product confirme d the first occurrence of CpGV from India. Thus, CpGV will form an important non-chemical strategy for managing this pest.

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Onyx versus coil embolization for the treatment of type II endoleaks

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This retrospective, single-center, study of 57 patients undergoing 77 embolization procedures for type II endoleaks after endovascular aortic aneurysm repair found a lower rate of reintervention in patients treated with Onyx compared to coil embolization.
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Estimation of Iron Content and Its Contribution in Iron-Fortified Food Products Consumed by School Children in Sri Lanka

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Iron fortification is an effective strategy that can be implemented to ensure supply and intake of iron for the public at large. Even though iron-fortified foods are widely available in the Sri Lankan market, the quantification of iron in those foods is not under the regulations of the food authorities in Sri Lanka. Therefore, this study aims to quantify the concentration of iron in selected iron-fortified foods available in the local market and determine their contribution to the recommended daily allowances (RDA) per serving. The iron content in most popular powdered milk, biscuits, and breakfast cereals among the children of 15-16 years in Horana Divisional Secretariat was analyzed using atomic absorption spectroscopy, and its contribution to RDA was calculated. The average iron values of iron-fortified milk powder (IFMP), iron-fortified biscuit (IFB), and iron-fortified breakfast cereals (IFBC) were found to be 18.08 ± 9.53, 7.88 ± 0.07, and 17.78 ± 7.47  mg/100 g, respectively. The average estimated daily intake (EDI) per serving of IFMP, IFB, and IFBC was 3.61 ± 1.75, 2.13 ± 0.06, and 5.60 ± 1.45 mg, respectively. The highest contribution to the RDA can be obtained by a single serving of IFBC. Only less than half of the tested products have compatible iron levels with their labeled information. Iron-fortified foods which were studied have a high amount of iron, and they can make from 5% to 35% contribution to RDAs in young children, adolescents, and adults even by a single serving.
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Sedum sarmentosum Total Flavonoids Alleviate Schistosomiasis-Induced Liver Fibrosis by Altering TGF-β1 and Smad7 Expression

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Objectives. Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. Methods. Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also meas ured the expression of transforming growth factor-beta 1 (TGF-β1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. Results. Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis (). Each dose of SSTF also significantly reduced TGF-β1 protein expression and mRNA levels in the liver tissues (). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels (). Immunohistochemistry showed that each dose of SSTF reduced TGF-β1 protein expression ().Conclusion. Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-β1/Smad7 pathway.
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