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An accompanying preprint in bioRxiv [https//doi.org/10.1101/2020.08.03.234872] describes the synthesis of the cyclic peptide and the experimental validation as an inhibitor of SARS-CoV-2 Mpro.
The pathomechanism of low back pain (LBP) remains unknown. Unilateral LBP patients have demonstrated ipsilateral morphological and material property changes within the lumbar soft tissues, potentially leading to asymmetric tissue loading. Through the comparison of healthy and unilateral LBP validated finite element models (FEMs), this study investigates potential stress shielding consequential of spinal tissue property augmentation.

Two FEMs of the musculoskeletal system - one demonstrating healthy and unilateral LBP conditions - were developed undergoing 30-degree flexion. FEMs included the vertebrae, intervertebral discs, and soft tissues from L1-S1. Material properties selected for the soft tissues were retrieved from published literature. To reflect unilateral LBP, the paraspinal morphology was atrophied, while the tissue moduli were increased. The symptomatic thoracolumbar fascia (TLF) was uniformly increased. Validation of the models preceded testing.

Model validation in spinal flexion was accomplteral LBP tissues. Consequentially, symptomatic paraspinal muscles may be unable to withstand loading, leading to stress shielding.Borderline personality disorder (BPD) is a severe psychiatric disorder accompanied by multiple comorbidities. Neuroimaging studies have identified structural abnormalities in BPD with most findings pointing to gray matter volume reductions in the fronto-limbic network, although results remain inconsistent. Similar alterations were found in posttraumatic stress disorder (PTSD), a common comorbidity of BPD. Only a small number of studies have investigated structural differences in BPD patients regarding comorbid PTSD specifically and studies conducting additional surface analyses are scarce. We investigated structural differences in women with BPD with and without PTSD and non-patient controls. Automated voxel-based and region-based volumetric analyses were applied. Additionally, four surface-based measures were analyzed cortical thickness, gyrification index, fractal dimension, and sulcus depth. Analyses did not identify cortical volume alterations in the fronto-limbic network. Instead, hypergyrification was detected in the right superior parietal cortex in BPD patients compared to non-patient controls. No distinction was revealed between BPD patients with and without PTSD. These findings underline the importance of a holistic investigation examining volumetric and surface measures as these might enhance the understanding of structural alterations in BPD.Toxicokinetic (TK) models refer to the process of contaminant bioaccumulation as a balance between rate of uptake from different sources (e.g., water or food), and rate of elimination via different processes such as excretion, growth and/or biotransformation. Biotransformation can considerably modify the fate of chemicals in an organism, especially their bioavailability, residence time, and toxicity. Invertebrate models generally neglect this process as they assume a low metabolic activity. However, some species such as Gammarus sp. amphipods are able to metabolize a vast range of organic compounds. Some recent TK models include biotransformation, but they prove limited for estimating related parameters by giving negative values and/or large uncertainties for biotransformation rate(s). Here we propose a generic TK model accounting for biotransformation using a Bayesian framework for simultaneously estimating the parameters. We illustrated the added value of our method by fitting this generic TK model to 22 puquired.The production of large amounts of synthetic industrial and biomedical compounds, together with environmental pollutants, poses a risk to our ecosystem and induces negative effects on the health of wildlife and human beings. With the emergence of the global problem of chemical contamination, the adverse biological effects of these chemicals are gaining attention among the scientific communities, industry, governments, and the public. Among these chemicals, endocrine disrupting chemicals (EDCs) are regarded as one of the major global issues that potentially affecting our health. MP-424 There is an urgent need of understanding the potential hazards of such chemicals. Zebrafish have been widely used in the aquatic toxicology. In this review, we first discuss the strategy of transgenic lines that used in the toxicological studies, followed by summarizing the current omics approaches (transcriptomics, proteomics, metabolomics, and epigenomics) on toxicities of EDCs in this model. We will also discuss the possible transgenerational effects in zebrafish and future prospective of the integrated omics approaches with customized transgenic organism. To conclude, we summarize the current findings in the field, and provide our opinions on future environmental toxicity research in the zebrafish model.Neuronal Ca2+ signals are fundamental for synaptic transmission and activity-dependent changes in gene expression. Voltage-gated Ca2+ channels and N-methyl-d-aspartate receptors play major roles in mediating external Ca2+ entry during action potential firing and glutamatergic activity. Additionally, the inositol-1,4,5-trisphosphate receptor (IP3R) and the ryanodine receptor (RyR) channels expressed in the endoplasmic reticulum (ER) also contribute to the generation of Ca2+ signals in response to neuronal activity. The ER forms a network that pervades the entire neuronal volume, allowing intracellular Ca2+ release in dendrites, soma and presynaptic boutons. Despite its unique morphological features, the contributions of ER structure and of ER-shaping proteins such as atlastin - an ER enriched GTPase that mediates homotypic ER tubule fusion - to the generation of Ca2+ signals in dendrites remains unreported. Here, we investigated the contribution of RyR-mediated Ca2+ release to IP3-generated Ca2+ signals in dendrites of cultured hippocampal neurons. We also employed GTPase activity-deficient atlastin-2 (ATL2) mutants to evaluate the potential role of atlastin on Ca2+ signaling and ER-resident Ca2+ channel distribution. We found that pharmacological suppression of RyR channel activity increased the rising time and reduced the magnitude and propagation of IP3-induced Ca2+ signals. Additionally, ATL2 mutants induced specific ER morphological alterations, delayed the onset and increased the rising time of IP3-evoked Ca2+ signals, and caused RyR2 and IP3R1 aggregation and RyR2 redistribution. These results indicate that both RyR and ATL2 activity regulate IP3-induced Ca2+ signal dynamics through RyR-mediated Ca2+-induced Ca2+ release, ER shaping and RyR2 distribution.
The standardized mortality ratio (SMR) of epilepsy in Asia ranges from 2.5 to 5.1. However, there are no such published data in Malaysia to date. Understanding the mortality rate and related factors will allow us to better assess and monitor the health status of PWE, thereby, preventing premature deaths among PWE. Hence, this study aimed to determine the mortality rate of adults with epilepsy (PWE) at the University Malaya Medical Centre (UMMC), a tertiary hospital in Malaysia.

A total of 2218 PWE were recruited retrospectively into this study. Deceased cases from 2009-2018 were identified from the National Registry Department of Malaysia. Age-, gender-, and ethnic-specific SMR were calculated.

There was a total of 163 deaths, of which 111 (68.1%) were male. The overall case-fatality rate (CFR) was 7.3%. Male PWE had higher CFR (9.2%) compared to females (5.1%, p<0.001). The annual death rate of PWE was 867 per 100, 000 persons. The overall all-cause SMR was 1.6 (CI 95% 1.3-1.8). The SMR for younger es.
The mortality rate of PWE in Malaysia is higher than that of the general population but lower compared to other Asian countries. Specifically, the rates are higher in the younger age group, male gender, and Indian ethnicity. Those with focal epilepsy, structural causes and uncontrolled seizures have higher mortality rates.
To compare auras between three groups of people with seizures [i.e., Idiopathic generalized epilepsies (IGE) vs. Temporal lobe epilepsy (TLE) vs. Functional seizures (FS)].

All patients, 10 years of age or older, with a diagnosis of IGE, TLE, or FS were prospectively registered in an electronic database and retrospectively studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020.

One thousand and three hundred ninety-one patients were studied (480 with IGE, 617 with TLE, and 294 with FS). Among patients with TLE, 63.5% of individuals reported auras; this figure was 68% in the FS and 12.7% in the IGE groups (p < 0.00001). Odds ratio of having auras in the TLE group compared with the IGE group was 11.96 (95% CI 8.73-16.39; p = 0.0001). Odds ratio of having auras in the TLE group compared with the FS group was 0.81 (95% CI 0.61-1.10; p = 0.1840). Odds ratio of having auras in the FS group compared with the IGE group was 14.61 (95% CI 10.15-21.02; p = 0.0001). The following auras were more frequent among patients with TLE emotional, cognitive, epigastric, and olfactory/gustatory. The following auras were more frequent among patients with FS headache and dizziness/vertigo.

Auras are not specific to focal epilepsies. Future studies should investigate auras in large cohorts of patients with focal or generalized epilepsies and also those with FS to determine the exact clinical value of each aura.
Auras are not specific to focal epilepsies. Future studies should investigate auras in large cohorts of patients with focal or generalized epilepsies and also those with FS to determine the exact clinical value of each aura.
To identify prognostic factors and long-term seizure outcomes for patients with tuberous sclerosis complex (TSC) who underwent resective treatment for epilepsy.

We enrolled 81 patients with TSC who had undergone resective epilepsy surgery at Sanbo Brain Hospital, Capital Medical University, between April 2004 and June 2019. We estimated cumulative probability of remaining seizure-free and plotted survival curves. Variables were compared using Mann-Whitney U, Pearson's correlation, continuity correction, and Fisher's exact chi-square tests. Prognostic predictors were analysed using log-rank (Mantel-Cox) tests and Cox regression models.

At the last follow-up, 48 (59.3%) patients were classified as International League Against Epilepsy Class 1 (including 14 patients who had seizures <3 times postoperatively on the same or different day and were seizure-free at all other times). The estimated cumulative probability of remaining seizure-free postoperatively was 69.0% (95% confidence interval [CI] 58.8-79.2%), 61.9% (95% CI 51.1-72.7%), and 55.0% (95% CI 42.8-67.2%) at 2, 5, and 10 years, respectively. The mean time of remaining seizure-free was 7.24 ± 0.634 years (95% CI 6.00-8.49); en bloc resection was an essential positive predictor of postoperative seizure freedom, as was age at seizure onset, regional interictal video-electroencephalography pattern, and temporal lobe surgery. The longer the seizure-free time, the less likely a relapse. Patients who postoperatively experienced seizures remained likely to recover.

We demonstrated the efficacy of surgical treatment for patients with TSC and intractable epilepsy. Detailed perioperative tests are a reliable predictor of postoperative seizure freedom.
We demonstrated the efficacy of surgical treatment for patients with TSC and intractable epilepsy. Detailed perioperative tests are a reliable predictor of postoperative seizure freedom.
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