Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Topical glaucoma medications – Clinical implications for the ocular surface

Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

Insight towards Nucleation Mechanism and Change in Morphology for Nanostructured Platinum Thin Film Directly Grown on Carbon Substrate via Electrochemical Deposition

Nanocrystalline platinum with different morphologies is synthesized via electrochemical deposition technique. The nucleation mechanism and its structural effect over the electrodeposited Pt on carbon electrodes have been systematically studied. Powder X-ray diffraction, X-ray photoelectron spectroscopy, and field-emission scanning electron microscopy are employed to study nucleation, oxidation states, and Pt structure growth on a carbon electrode. This study reports significant development of Pt metal nanoparticles with different morphologies such as a sphere, flower, core-flower, and rod-like structure directly fabricated on carbon electrode while tuning the deposition parameters such as current density, time, temperature, pH during the deposition process. The proposed electrochemical route represents a superior fabrication procedure for large-scale electrode fabrication compared to a conventional method for preparing membrane electrode assemblies for fuel cell stacks.     

Association of meibomian gland architecture and body mass index in a pediatric population

PurposeTo determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI).MethodsProspective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0–4) for gland atrophy and a 3-point score (0–2) for gland tortuosity.Results175 eyes of 175 participants aged 4–17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0–4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0–2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m² with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99–1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00–1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17–12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r² = 0.04).ConclusionIn this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients.