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Chronic and heavy ketamine use has been associated with persistent neurocognitive impairment and structural brain abnormalities. Blood levels of neurofilament light chain (NFL) was recently proposed as a measure of axonal integrity in several neuropsychiatric disorders. We aimed to characterise the axonal neurotoxicity of chronic ketamine use and its relationship to relevant clinical outcomes.
We enrolled 65 treatment-seeking ketamine-dependent patients (55 males and 10 females) and 60 healthy controls (51 males and 9 females). Blood NFL levels measured by single molecule array (SiMoA) immunoassay. We compared NFL levels between groups and used regression analyses to identify clinical variables related to NFL levels.
Ketamine-dependent patients had significantly higher NFL levels compared to controls (
< 0.001). A multivariate regression showed that age (
< 0.05) and lifetime history of major depressive disorder (MDD) (
< 0.01) predicted high NFL blood levels in patients. Subsequent group comparisons showed that specifically ketamine-dependent patients with a lifetime history of MDD had significantly increased NFL levels than those without (
< 0.05).
These results suggest substantial neuroaxonal alterations following chronic and heavy ketamine use. The pronounced increase of NFL levels in the MDD subgroup warrants further investigation of a potential neuroaxonal vulnerability of depressed patients to ketamine.
These results suggest substantial neuroaxonal alterations following chronic and heavy ketamine use. The pronounced increase of NFL levels in the MDD subgroup warrants further investigation of a potential neuroaxonal vulnerability of depressed patients to ketamine.
We evaluated the imaging and functional outcomes of anatomic stemless shoulder arthroplasty (ECLIPSE) in elderly patients with primary osteoarthritis of the glenohumeral joint in Asian developing countries.
Thirty patients were treated using stemless TSA in 26months period (years 2017 and 2019), and were followed for a minimum of 24months. Functional outcomes were assessed using Constant and ASES scores. Radiolucent lines and osteopenia were analyzed on radiographs.
Pre-surgery Constant and ASES scores improved from 27.33(21-38) and 29.67(22-38) to 68(54-78) and 71(71.4(56-79) at final follow up. Around the humeral component, one patient had calcar thinning and a radiolucent line thicker than 2 mm, while six patients had radiolucent lines less than 2 mm. The mean glenoid radiolucency score was 2± 1.1.
In our setting, stemless total shoulder arthroplasty demonstrated significant improvement in functional scores at short- to mid-term follow-up. Chaetocin cost Radiographic findings did not correlate with functional scores.
In our setting, stemless total shoulder arthroplasty demonstrated significant improvement in functional scores at short- to mid-term follow-up. Radiographic findings did not correlate with functional scores.
Suicide is a major public health problem and it has a prominent genetic component. We performed a genome-wide association study (GWAS) of suicidal behaviour severity.
Suicide behaviour severity was assessed within the Schedules for Clinical Assessment in Neuropsychiatry in our mood disorder sample (
= 3506) for the GWAS. We also performed polygenic risk score analyses to explore genetic sharing between suicidal behaviour severity and a number of phenotypes, including bipolar disorder, major depressive disorder, alcoholism, post-traumatic stress disorder, impulsivity, insomnia, educational attainment, loneliness, maltreatment, and amygdala volume.
We did not detect genome-wide significant findings at the single-marker or gene level. We report a number of suggestive single-marker and gene-based findings. Our polygenic risk score analyses did not yield significant findings with these phenotypes.
Larger sample sizes are required to detect moderate effects.
Larger sample sizes are required to detect moderate effects.Introduction Steroid sulfatase (STS) enzyme is responsible for transforming the inactive sulfate metabolites of steroid sex hormones into the active free steroids. Both the deficiency and the over-expression of STS are associated with the pathophysiology of certain diseases. This article provides the readership with a comprehensive review about STS enzyme and its recently reported inhibitors.Areas covered In the present article, we reviewed the structure, location, and substrates of STS enzyme, physiological functions of STS, and disease states related to over-expression or deficiency of STS enzyme. link2 STS inhibitors reported during the last five years (2016-present) have been reviewed as well.Expert opinion Irosustat is the most successful STS inhibitor drug candidate so far. It is currently under investigation in clinical trials for treatment of estrogen-dependent breast cancer. Non-steroidal sulfamate is the most favorable scaffold for STS inhibitor design. They can be beneficial for the treatment of hormone-dependent cancers and neurodegenerative disorders without significant estrogenic side effects. Moreover, dual-acting molecules (inhibitors of STS + another synergistic mechanism) can be therapeutically efficient.
To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on suicide-related outcomes within one-week or one-month in individuals with current suicidal ideation (SI) or a recent suicide attempt (SA).
We performed a database (Medline, Academic Search Complete, PsycARTICLES, the Cochrane library, PubMed) and manual reference search for randomised controlled trials, published between March 2000 and March 2020. Antisuicidal efficacy was defined as SI, SA, or a closely related concept. Quality was assessed with the Cochrane Risk of Bias 2 tool for randomised trials.
Out of 34 trials, five reported ketamine or esketamine superiority over placebo in reducing SI in depressed subjects within one week, while five studies had negative findings. Single trials reported positive results for one-month antisuicidal efficacy of buprenorphine, paroxetine, a crisis response plan, and assertive case management. Most trials were underpowered and had moderate-to-high risk of bias.
Preliminary mixed evidence suggests the possible utility of several pharmacological (ketamine, esketamine paroxetine, and buprenorphine) and non-pharmacological (a crisis response plan, and assertive case management) interventions. Only the immediate efficacy of ketamine was supported by multiple studies, and replication is needed.
Preliminary mixed evidence suggests the possible utility of several pharmacological (ketamine, esketamine paroxetine, and buprenorphine) and non-pharmacological (a crisis response plan, and assertive case management) interventions. Only the immediate efficacy of ketamine was supported by multiple studies, and replication is needed.
Hepatocellular carcinoma (HCC) is a malignant tumour with high mortality. In recent years, microRNA (miRNA) has been recognized in the diagnosis and prognosis of cancer. miR-487b has been found to play a role in a variety of cancers. The purpose of this study is to explore the role of miR-487b in the diagnosis and prognosis of hepatitis B virus (HBV)-related HCC, and its influence on the biological behaviour of HCC cells.
Quantitative real-time polymerase chain reaction (qRT-PCR) method was used to detect the expression level of miR-487b in the serum of HCC patients, HBV patients, and healthy people. The ROC curve was used to evaluate the role of miR-487b in the diagnosis of HCC. The prognostic significance of miR-487b in HCC was analyzed by the Kaplan-Meier survival curve and Cox regression model. The effects of miR-487b on cell proliferation, migration, and invasion were explored through MTT assay and transwell assays.
The expression level of miR-487b in the serum of HBV-related HCC patients was significantly higher than that of CHB patients and normal healthy people. The expression level of miR-487b can distinguish HCC patients from CHB patients or normal healthy people. High expression of miR-487b was associated with poor prognosis, which could be used as an independent prognostic factor for HCC. The upregulation of miR-487b promoted cell proliferation, migration, and invasion.
miR-487b can be used as a biomarker for the diagnosis and prognosis of HCC.
miR-487b can be used as a biomarker for the diagnosis and prognosis of HCC.
Percutaneous balloon compression is a safe and effective treatment for trigeminal neuralgia. Current technique consists of penetrating the foramen ovale using a sharp 14G needle with a stylet. Difficulty of cannulation of the foramen ovale, failures of cannulation and major neurovascular complications of the procedure, although rare, may be due to the relatively large caliber of this needle and its sharp tip.
To present a novel technique to facilitate and make the cannulation of the foramen ovale with a 14G cannula safer.
A rigid blunt-tip guide of 1.2 or 1.5 mm is used to penetrate the foramen ovale under lateral fluoroscopic control. link3 Once the guide enters the foramen it is advanced further to the clival line, and a 14G cannula is then advanced over the guide to engage the foramen, at which point the guide is withdrawn and replaced with the balloon catheter.
The technique was employed to deliver a 4F balloon catheter to Meckel's cave successfully in 500 consecutive procedures performed on 416 trigemiernous fistula or intracranial hemorrhage in this series of patients suggests that the technique may be safer than the use of conventional sharp tipped 14G needles in terms of avoiding neurovascular complications.Adolescent survivors of pediatric brain tumor (PBT) are a sparsely studied subset of childhood cancer survivors. Sustaining a PBT may complicate the development of executive functions (EFs), which play a vital role in long-term psychosocial adjustment. In this study, 48 adolescent survivors and their parents completed questionnaires assessing EF, psychological symptoms, fatigue, and adaptive functioning, and 26 survivors underwent neuropsychological assessment. Survivors reported significantly more problems with adaptive functioning than a healthy control group, and this was most strongly associated to executive dysfunction, compared to psychological symptoms and fatigue. The findings have important implications for long-term follow-ups.Introduction Transsphenoidal surgery is the first-line treatment for acromegaly, but even in referral centers, approximately 50% of patients are not cured, and adjuvant pharmacological treatment is necessary. Widely used therapies encompass different drug classes, such as injectable somatostatin receptor ligands (SRLs), oral dopamine agonists and injectable growth hormone receptor antagonists, but approximately 40% of patients still have disease activity in real-life practice. Therefore, there is a need for new medical therapies to allow disease control in a larger proportion of patients, increase quality of life, reduce morbidity and mortality and improve treatment adherence in acromegaly.Areas covered In this review, the authors cover new and emerging drugs under development or drugs recently approved for the treatment of acromegaly.Expert opinion Disease control is essential to reduce morbidity and mortality in acromegaly but is still not achieved in a significant proportion of patients or takes a long time to be achieved with currently available options and treatment algorithms.