The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.
Abstract. The insulin-like growth factor 1 receptor (IGF1R) pathway plays an important role in the pathogenesis of non-small cell lung cancer (NSCLC) and also provides a mechanism of resistance to targeted therapies. IGF1R is therefore an ideal therapeutic target and several inhibitors have entered clinical trials. However, thus far the response to these inhibitors has been poor, highlighting the importance of predictive biomarkers to identify patient cohorts who will benefit from these targeted agents. It is well-documented that mutations and/or deletions in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain predict sensitivity of NSCLC patients to EGFR TK inhibitors. Single-nucleotide polymorphisms (SNPs) in the IGF pathway have been associated with disease, including breast and prostate cancer. The aim of the present study was to elucidate whether the IGF1R TK domain harbours SNPs, somatic mutations or deletions in NSCLC patients and correlates the mutation status to patient clinicopathological data and prognosis. Initially 100 NSCLC patients were screened for mutations/deletions in the IGF1R TK domain (exons 16-21) by sequencing analysis. Following the identification of SNP rs2229765, a further 98 NSCLC patients and 866 healthy disease-free control patients were genotyped using an SNP assay. The synonymous SNP (rs2229765) was the only aberrant base change identified in the IGF1R TK domain of 100 NSCLC patients initially analysed. SNP rs2229765 was detected in exon 16 and was found to have no significant association between IGF1R expression and survival. The GA genotype was identified in 53.5 and 49.4% of NSCLC patients and control individuals, respectively. No significant difference was found in the genotype (P= 0.5487) or allele (P=0.9082) frequencies between the case and control group. The present findings indicate that in contrast to the EGFR TK domain, the IGF1R TK domain is not frequently mutated in NSCLC patients. The synonymous SNP (rs2229765) had no significant association between IGF1R expression and survival in the cohort of NSCLC patients. IntroductionThe role of the insulin-like growth factor 1 receptor (IGF1R) in the pathogenesis of malignant epithelial tumours, including non-small cell lung cancer (NSCLC), has been well-characterised (1-5). Activation of this receptor pathway promotes tumour growth by inhibition of apoptosis, transformation, metastasis and induction of angiogenesis through vascular endothelial growth factor (6-10).IGF1R is frequently overexpressed in NSCLC patients, however, there is controversy over its significance as a prognostic marker. Certain studies have shown no correlation between high IGF1R expression and patient survival (3,4); conversely, other studies have demonstrated that high IGF1R expression was associated with nodal metastasis, recurrence and a significantly poorer overall survival (OS) rate in NSCLC patients (11,12). A recent meta-analysis suggests IGF1R positive expression as an adverse factor for disease-free survival (DFS) in NSCLC pat...
Background While traumatic childhood experiences have been frequently associated with adverse effects on social cognitive abilities, specifically emotion recognition, in individuals with schizophrenia (SZ) and to some degree in healthy adults also (Rokita et al., 2018), the neural mechanisms for this association remain unclear. Therefore, the main aim of this study was to explore the impact of childhood trauma on brain structures that are particularly sensitive to stress and are involved in emotion recognition processes (i.e. amygdala, hippocampus, anterior cingulate cortex (ACC)) (Cancel et al., 2019). We also investigated whether volumetric changes in these brain regions mediate the association between childhood trauma and performance on an emotion recognition task. Methods We investigated 46 patients with SZ (mean age=43.74; SD=10.94; 12 females and 34 males) and 112 healthy adults (mean age=40.13; SD=12.46; 31 females and 81 males). All participants underwent an MRI scan and completed the Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 2003), which assesses the experience of trauma in childhood, including emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. Emotion recognition was measured with the total score on the Emotion Recognition Task (ERT) implemented in the Cambridge Neuropsychological Test Automated Battery (CANTAB) (Robbins et al., 1994). Mediation analyses were conducted to explore the direct and indirect effects of childhood trauma on emotion recognition via volumetric changes in the amygdala, hippocampus and the ACC as mediators. Results We found that patients with SZ had significantly higher scores on physical neglect (PN; p=.018) and cumulative childhood trauma (p=.049) compared to healthy participants. Patients also had significantly smaller hippocampus (p=.001), but not amygdala (p=.453) or ACC (p=.893), and performed worse on the ERT task (p<.001), compared to the healthy group. PN was significantly negatively associated with the total score on the ERT task (r=-.321, p<.001) and a smaller volume of the left ACC (r=-.161, p=.046) in all participants. Reduced volumes of the left and entire ACC appeared to mediate the association between PN and ERT task in healthy adults (β=-1.183, SE=.687, 95% [-2.701: -.079]; β=-1.176, SE=.738, 95% [-2.872: -.0162], respectively). In the patient group, only the direct association between PN and the ERT score was significant (β= -11.657, SE=3.843, 95% CI [-19.251: -4.064], p=.003). Discussion Our findings provide further evidence for the detrimental impact of childhood trauma, specifically physical neglect, on volumetric changes in the ACC region in both patients with SZ and healthy adults. Moreover, to the best of our knowledge, this is the first study to show that the ACC region may be a potential neural mediator in the association between physical neglect and the ability to recognise emotions. These findings highlight the need to develop early interventions (e.g. parenting programs) in order to minimise the occurrence of childhood adversities, hence preventing from their detrimental effects on brain structure and function in both clinical and non-clinical populations.
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