GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC.     

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.     

Contralateral replacement of pacemaker and leads following laser sheath extraction and concomitant stenting for superior vena cava syndrome

We present the case of a 61-year-old man with a history of pacemaker implantation 15 years ago. The patient was admitted with chronic swelling of the right hemithorax and inflammation of the old incision scar after the replacement of pacemaker generator 6 years ago. The patient also presented symptoms and clinical signs of superior vena cava syndrome. Computed tomography of the thorax showed obstruction of the superior vena cava. The surgical procedure consisted of extraction of infected pacemaker system with excimer laser technique followed by dilatation and stenting of the SVC and finally implantation of a new permanent pacemaker system on the left side.     

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (¹H-MRSI). T1- and T2-weighted MRI images and three-dimensional ¹H-MRSI (480 voxels over 360 cm³, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This ¹H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.     

Placement of a subdural evacuating port system for management of iatrogenic hyperacute subdural hemorrhage following intracranial monitor placement

A 22-year-old man was admitted with a severe traumatic brain injury developed a hyperacute subdural hematoma (SDH) following attempted brain tissue oxygen monitor placement. This patient was successfully treated by placement of a subdural evacuation portal system (SEPS). The patient presented to a Level I trauma center after a severe bike versus auto accident. On admission, he was found to have a Glasgow Coma Scale (GCS) score of 3. The patient had small areas of intraparechymal hemorrhage as well as suspicion for diffuse axonal injury in the midbrain. Based on the patient’s GCS score, neurological monitoring was indicated as a part of his intensive care unit treatment, however a SDH occurred during an attempted placement of a brain tissue oxygen monitor. This iatrogenic hyperacute SDH after burr hole monitoring device placement was treated with a SEPS drain. The SEPS drain has been shown to provide complete and/or temporary decompression of liquefied SDH. To our knowledge, this is the first report of using the SEPS to treat iatrogenic SDH associated with an intracranial monitoring device. This technique should be added to the armament of treatment options for a neurosurgeon to treat or temporize a hyperacute SDH with increased intracranial pressure in specific patients.     

Foveal vision is impaired in Parkinson's disease

PurposeThe article aims to review foveal involvement in Parkinson's disease.ScopeClinical observations as well as electrophysiological and anatomical studies in animal models provide evidence that Parkinson's disease (PD) affects vision. The retina is the most distal locus of visual dysfunction in PD as shown by electroretinographic (ERG) and optical coherence tomographic (OCT) studies. Thinning of the retinal nerve fibre layer (RNFL) and the fovea has been reported in PD. This review summarises retinal physiology and foveal visual dysfunction in PD and quantification of retinal thinning as reported in different studies and using different instruments. At this point due to methodological diversity and relatively low number of subjects studied, a meta-analysis is not yet possible. Results obtained on one equipment are not yet transferable to another. The author also briefly alludes to some links of visual processing deficits beyond visual detection, such as visual discrimination, visual categorisation and visuospatial orientation in PD.ConclusionsThere are some promising results suggesting the potential applicability of ST-Oct as a biomarker in PD. Furthermore, these data raise some interesting neurobiological questions. However, there are identifiable pitfalls before OCT quantification may be used as a biomarker in PD. Analysis standardisation is needed on a larger than existing healthy and patient population. Furthermore, longitudinal studies are needed. The exact relationship between retinal foveal deficits and visuo-cognitive impairment in PD remains a challenging research question.     

A Comparative Assessment of Suicide Risk for Young People in Youth Detention

The aim of this study was to compare levels of agreement in the assessment of suicide risk by detention center staff procedures compared with those completed by a mental health clinician. Over a 6-month period, 64 young people (mean age 15.0 years; SD+/?1.3) assessed as being acutely suicidal were referred for a clinical mental health assessment and completion of the Adolescent Suicide Questionnaire (ASQ). Cohen's kappa statistic was used to determine inter-judgmental agreement between the detention center, a clinical assessment and ASQ scores. Weak levels of agreement existed in the assessment of suicide. We recommend further work in this area and broad discussion toward development of national guidelines to standardize the assessment of suicide risk for young people in youth detention.     

Preoperative localization of lung nodules: a comparative analysis of hookwire and radio-guided procedures

BackgroundHistological diagnosis of pulmonary nodules requires surgical resection on many occasions. There are multiple localization strategies each with their own benefits and complications. The objective of this study is to compare preoperative lung nodule localization with hookwire and radiotracer injection (radioguided occult lesion localization, ROLL). To compare results, complications, and volume of the sample resected with both techniques.MethodsPatients undergoing resection of pulmonary nodules with video-assisted thoracoscopy and pre-surgical localization with hookwire or ROLL were studied. Eighty-eight pulmonary nodules were resected in 76 patients: 52 with a hook wire and 36 with a radiotracer. The localization rate, the shortest distance between the nodule and the pleura, the intrapulmonary distance of the locator, the complications, the volume of the resection piece, and the histological result were all assessed. In addition, the factors that influence the volume of the surgical piece were analyzed.ResultsAll the nodules were resected with both techniques. The intrapulmonary path of the locator is longer for the ROLL group (23.91 vs. 16.28 mm; P=0.04), with no differences in the distance from the nodule to the pleura. The rate of pneumothorax was significantly higher after the placement of a hook wire (69.2% vs. 24.2%; P<0.0001), while there were no differences in the presence of hemorrhage. The volume of the pieces resected using ROLL was more minor than with hookwire, although not statistically significant (20.19 vs. 34.26 cc; P=0.07).ConclusionsPreoperative localization with the ROLL technique is safer than the placement of hookwire. In addition, the ROLL technique shows a tendency to obtain a smaller volume of resected tissue since the marking is not affected by the intrapulmonary route used during marker placement. ROLL technique allows to locate lung nodules with fewer complications than hookwire and probably gets smaller resection samples.