The results obtained strengthen the evidence of the toxicity associated to surfynol; therefore, reinforcing the need for a more comprehensive study on the viability of its use in food packaging.Previously, we published selected Eliciting Dose (ED) values (i.e. ED01 and ED05 values) for 14 allergenic foods, predicted to elicit objective allergic symptoms in 1% and 5%, respectively, of the allergic population (Remington et al., 2020). These ED01 and ED05 values were specifically presented and discussed in the context of establishing Reference Doses for allergen management and the calculation of Action Levels for Precautionary Allergen Labeling (PAL). In the current paper, we publish the full range of ED values for these allergenic foods and provide recommendations for their use, specifically in the context of characterizing risks of concentrations of (unintended) allergenic proteins in food products. The data provided in this publication give risk assessors access to full population ED distribution information for 14 priority allergenic foods, based on the largest threshold database worldwide. The ED distributions were established using broad international consensus regarding suitable datapoints and methods for establishing individual patient's NOAELs and LOAELs and state of the art statistical modelling. Access to these ED data enables risk assessors to use this information for state-of-the-art food allergen risk assessment. This paper contributes to a harmonization of food allergen risk assessment and risk management and PAL practices.Di-(2-ethylhexyl) phthalate (DEHP), which is widely used as an industrial plasticizer, may cause liver damage. Concomitantly, bad dietary habits can exacerbate the liver burden. In this study, high-fat diet (HFD)-fed rats were treated with DEHP (10, 100, or 300 mg/kg bw) for 5 weeks, and a biochemical method was adopted to detect serum lipid contents. Key metabolic genes and pathological changes were assessed by different methods (RT-PCR, Western Bloting, ELISA and HE staining). The rats which were exposed to DEHP at a dose of 10 mg/kg bw exhibited dyslipidemia and increased transcription of SREBP-1 and its target FAS, thereby prompting de novo lipogenesis, but they did not become obese. Instead, DEHP at a dose of 300 mg/kg bw elevated the levels of AMPK phosphorylation and the mRNA levels of PPAR-α, PGC-1α, CPT-1 and lipin-1 in the liver, which led to fatty acid oxidation. Additionally, DEHP at the highest dose increased the TNF-α mRNA expression in the liver. Based on these findings, we conclude that excess fatty acid oxidation might increase the inflammatory response. No toxic effects on hepatic function were observed. These findings suggest that different doses of DEHP have the potential to disturb hepatic metabolic imbalance in HFD-fed rats.Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.
Repetitive transcranial magnetic stimulation (rTMS) is the current treatment option for major depression (MD). Theta-burst stimulation (TBS), a variation of rTMS, affords a short stimulation duration, low stimulation pulse intensity, and possibility to improve rTMS efficiency. This systematic review and meta-analysis examined the studies on efficacy and tolerability of TBS in patients with MD.
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature from 1990 until May 24, 2020, and performed a random-effects meta-analysis by including response and remission rates of depression and dropout rates as main outcome measures.
In total, 10 studies including 6 randomized controlled trials (RCTs; n=294) and 4 uncontrolled clinical trials (non-RCTs; n=297) were included. The overall effect size of response rate and remission rates were 0.38 (95% confidence interval [CI] 0.29-0.48) and 0.20 (95% CI 0.13-0.29), respectively. Notably, the TBS group showed favorable efficacy without major adverse events.
TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.
TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.
For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis.
Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation.
Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid rvel candidates for osteoarthritis biomarker development on a tissue-specific basis.Drug release systems co-encapusulated with ammonium bicarbonate (ABC) could facilitate drug release upon acidic or thermal stimulations to improve therapeutic effect. However, it is not easy to control drug release rate, owing to relative stable temperature and acidic condition in living body. Besides, the additional loaded ABC reduces drug loading capacity. Herein, a near-infrared light triggered rapid drug release system with high loading capacity was developed by loading ABC and doxorubicin into yolk-shell structured Au nanorods@mesoporous silica. Gas bubbles were generated from the thermolysis of ABC utilizing photothermal effect of Au nanorods to extrude drug molecules. The mesoporous silica shell was finally destroyed along with growing bubbles, resulting in burst drug release. The photothermal therapeutic effect of Au nanorods also contributed in tumor treatment. The excellent therapeutic effect was demonstrated in cancer cells and tumor-bearing mice, which provides a new reference to achieve controllable rapid drug release in cancer medicine.
Public health measures were instituted to reduce COVID-19 spread. A decrease in total emergency department volume followed, but the impact on injury is unknown. With lockdown and social distancing potentially increasing domicile discord, we hypothesized that intentional injury increased during COVID-19, driven primarily by an increase in penetrating trauma.
A retrospective review of acute adult patient care in an urban Level I trauma center assessed injury patterns. Presenting patient characteristics and diagnoses from 6 weeks pre to 10 weeks post statewide stay-at-home orders (March 16, 2020) were compared, as well as with 2015-2019. Subsets were defined by intentionality (intentional vs nonintentional) and mechanism of injury (blunt vs penetrating). Fisher exact and Wilcoxon tests were used to compare proportions and means.
There were 357 trauma patients that presented pre stay-at-home order and 480 that presented post stay-at-home order. https://www.selleckchem.com/products/Honokiol.html Pre and post groups demonstrated differences in sex (35.6% vs 2 violence. Meanwhile, emergency department and nonintentional trauma visits decreased. Pandemic-related public health measures should embrace intentional injury prevention and management strategies.Lidocaine induces neurotoxicity in the spinal cord, but the underlying mechanisms remain unclear. In this study, we evaluated the effects of miR-199a-5p on 10 % lidocaine neurotoxicity. Increased expression of miR-199a-5p in the spinal cord of rats treated with 10 % lidocaine was assessed by qRT-PCR. Furthermore, after miR-199a-5p antagomir administration, the sensory dysfunction and myelin sheath lesions (evaluated by semithin sections stained with toluidine blue, electron microscopy, g-ratios and myelin thickness) induced by 10 % lidocaine were alleviated. Myelin regulatory factor (MYRF), a key molecule of myelin sheath development, was predicted to be a target gene of miR-199a-5p by the TargetScan and miRBase databases. MYRF and its downstream factors myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) were significantly decreased after intrathecal 10 % lidocaine administration. Moreover, these changes were reversed after miR-199a-5p antagomir administration. FISH-immunofluorescence showed coexpression of miR-199a-5p and MYRF in the spinal cord white matter of rats. A luciferase reporter assay further demonstrated the functional association between miR-199a-5p and MYRF. Overall, miR-199a-5p upregulation is involved in 10 % lidocaine-induced spinal cord toxicity through regulation of MYRF. Therefore, downregulating miR-199a-5p expression may be a potential strategy to ameliorate spinal cord neurotoxicity induced by 10 % lidocaine.Regorafenib (RGF) has a great success in the treatment of colorectal cancer, gastrointestinal stromal tumours and hepatocellular carcinoma by inhibiting angiogenic, stromal and oncogenic kinases. However, RGF can induce life-threatening cardiotoxicity including hypertension and cardiac ischemia/infarction. The molecular mechanism of the adverse effects has not been elucidated. Mitochondrial dysfunction is one of the major causes of cardiac diseases since cardiac cells highly need ATP for their contractility. Therefore, we aimed to investigate molecular mechanisms of RGF-induced cardiac adverse effects using H9c2 cell model by focusing on mitochondria. Cells were treated with 0-20 μM RGF for 48 and 72 h. According to our results, RGF inhibited cell proliferation and decreased the ATP content of the cells depending on the exposure time and concentration. Loss of mitochondrial membrane potential was also observed at high dose. Mitochondrial fusion/fission genes and antioxidant SOD2 (superoxide dismutase) gene expression levels increased at high doses in both treatments.