•It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19).•We found that diabetes was associated with an approximately ...4-fold increased risk of having severe/critical COVID-19 illness.•This association was independent of age, sex, obesity, hypertension and smoking.•These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.
Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been ...studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand (11)COMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer (11)COMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide (11)COMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively--OMAR VT, anandamide and cortisol--correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.
Summary
Long‐term prognosis varies widely among patients with hepatitis B virus (HBV)‐related liver cirrhosis. Our study aimed to investigate the applicability of albumin‐bilirubin (ALBI), Child‐Pugh ...and model for end‐stage liver disease (MELD) scores to the long‐term prognosis prediction of HBV‐related cirrhosis. Patients diagnosed with HBV‐associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long‐term outcome prediction for HBV‐related cirrhosis was compared with Child‐Pugh and MELD scores using time‐dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow‐up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child‐Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1‐year, 2‐year and 3‐year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child‐Pugh class. Thus, ALBI score was effective in predicting the long‐term prognosis for patients with HBV‐related cirrhosis and more accurate than Child‐Pugh and MELD scores.
Structured
Objectives
The objective of this study was to perform a systematic review of the orthodontic literature with regard to efficiency, effectiveness and stability of treatment outcome with ...clear aligners compared with treatment with conventional brackets.
Methods
An electronic search without time or language restrictions was undertaken in October 2014 in the following electronic databases: Google Scholar, the Cochrane Oral Health Group's Trials Register, Scopus, CENTRAL, MEDLINE via OVID, EMBASE via OVID and Web of Science. We also searched the reference lists of relevant articles. Quality assessment of the included articles was performed. Two authors were responsible for study selection, validity assessment and data extraction.
Results
Four controlled clinical trials including a total of 252 participants satisfied the inclusion criteria. We grouped the trials into four main comparisons. One randomized controlled trial was classified as level 1B evidence, and three cohort studies were classified as level 2B evidence. Clear aligners appear to have a significant advantage with regard to chair time and treatment duration in mild‐to‐moderate cases based on several cross‐sectional studies. No other differences in stability and occlusal characteristics after treatment were found between the two systems.
Conclusions
Despite claims about the effectiveness of clear aligners, evidence is generally lacking. Shortened treatment duration and chair time in mild‐to‐moderate cases appear to be the only significant effectiveness of clear aligners over conventional systems that are supported by the current evidence.
Background
The prevalence of allergic rhinitis (AR) has increased worldwide in recent decades. This study was conducted to investigate the prevalence of self‐reported AR and profiles of AR‐related ...comorbidities in the adult population of China over time.
Methods
This study surveyed residents of 18 major cities in mainland China. Telephone interviews were conducted with study participants after sampling target telephone numbers by random digit dialing. The questions asked during telephone interviews were based on those included in validated questionnaires and focused on topics regarding AR, nonallergic rhinitis (NAR), acute/chronic rhinosinusitis (ARS/CRS), asthma, and atopic dermatitis (AD).
Results
During 2011, a total of 47 216 telephone interviews were conducted, and the overall response rate was 77.5%. When compared with the AR prevalence in 11 cities surveyed in 2005, there was a significant increase in self‐reported adult AR in eight of those cities (P < 0.01). In 2011, the standardized prevalence of self‐reported adult AR in the 18 cities was 17.6%. The concentration of SO2 was positively correlated with the prevalence of AR (r = 0.504, P = 0.033). A multiple regression model showed that the absolute change in household yearly income was significantly associated with the change in the prevalence of AR (R2 = 0.68), after adjusting for PM10, SO2, NO2, temperature, and humidity. The overall prevalences of NAR, ARS, CRS, asthma, and AD in the general population were 16.4%, 5.4%, 2.1%, 5.8%, and 14%, respectively.
Conclusion
During a 6‐year period, there was a significant increase in the prevalence of self‐reported AR in the general Chinese adult population. The incidence of AR being accompanied by rhinosinusitis, asthma, or AD was significantly higher among individuals having self‐reported AR compared with the general population.
The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. ...In this study, we provide a cross pharmaceutical industry position on “how PBPK modeling can be applied in industry” focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.
Online hate and extremist narratives have been linked to abhorrent real-world events, including a current surge in hate crimes
and an alarming increase in youth suicides that result from social media ...vitriol
; inciting mass shootings such as the 2019 attack in Christchurch, stabbings and bombings
; recruitment of extremists
, including entrapment and sex-trafficking of girls as fighter brides
; threats against public figures, including the 2019 verbal attack against an anti-Brexit politician, and hybrid (racist-anti-women-anti-immigrant) hate threats against a US member of the British royal family
; and renewed anti-western hate in the 2019 post-ISIS landscape associated with support for Osama Bin Laden's son and Al Qaeda. Social media platforms seem to be losing the battle against online hate
and urgently need new insights. Here we show that the key to understanding the resilience of online hate lies in its global network-of-network dynamics. Interconnected hate clusters form global 'hate highways' that-assisted by collective online adaptations-cross social media platforms, sometimes using 'back doors' even after being banned, as well as jumping between countries, continents and languages. Our mathematical model predicts that policing within a single platform (such as Facebook) can make matters worse, and will eventually generate global 'dark pools' in which online hate will flourish. We observe the current hate network rapidly rewiring and self-repairing at the micro level when attacked, in a way that mimics the formation of covalent bonds in chemistry. This understanding enables us to propose a policy matrix that can help to defeat online hate, classified by the preferred (or legally allowed) granularity of the intervention and top-down versus bottom-up nature. We provide quantitative assessments for the effects of each intervention. This policy matrix also offers a tool for tackling a broader class of illicit online behaviours
such as financial fraud.
•The neuroprotection of ketamine at subanesthetic-dosage.•ketamine at sub-anesthetic dose alleviates functional deficits after TBI.•Posttraumatic administration of ketamine exerts anti-inflammatory ...properties.•ketamine at sub-anesthetic dose may regulate autophagy and ameliorate secondary brain injury.•Administration of 10mg/kg ketamine, every 24h up to 7days.
As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10mg/kg ketamine, every 24h up to 7days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p-mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.
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