Neuroendocrine Differentiation in Conventional Colorectal Adenocarcinomas: Incidental Finding or Prognostic Biomarker?

Background: Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrine differentiation. However, the biological behavior of adenocarcinomas that express synaptophysin but do not show a typical neuroendocrine morphology remains unclear. Methods: We investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival and compared the survival characteristics of synaptophysin expression groups to MANECs. Results: Synaptophysin expression in conventional colorectal adenocarcinomas was associated with a shortened disease-free survival (p = 0.037), but not with overall survival or disease-specific survival (DSS) in univariate analyses and without any survival impact in multivariate analyses. Patients with “true” MANECs, on the other hand, showed a significantly shorter survival than all conventional adenocarcinomas with or without synaptophysin expression in uni- and multivariate analyses (e.g., multivariate DSS: p < 0.001, HR: 5.20). Conclusions: Our study demonstrates that synaptophysin expression in conventional colorectal adenocarcinomas, in contrast to MANECs, is not associated with a significantly poorer clinical outcome when compared to adenocarcinomas without synaptophysin expression. Furthermore, our data suggest that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs, also strongly arguing that synaptophysin testing should be reserved for carcinomas with an H&E morphology suggestive of a neuroendocrine differentiation.

Is it time now to stop searching for other tumor markers for HCC apart from alpha-fetoprotein?

It’s a dilemma; does AFP still a standard marker in the diagnosis and prognosis of HCC or do we need another marker? Until now, no other tumor marker showed promising results in comparison to alpha-fetoprotein.

Lipidomic Analysis to Assess Oxidative Stress in Acute Coronary Syndrome and Acute Stroke Patients

Alterations in lipid metabolism mediated by oxidative stress play a key role in the process of atherosclerosis and superimposed thrombosis; these can lead to acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Multiple studies have shown that the formation of atheromatous lesions is initiated by oxidation of low-density lipoproteins incorporated into the intima of the vessel wall. Here, we studied lipids in plasma samples from three cohorts: 61 patients with ACS (group A), 49 patients with AIS (group D), and 82 controls (group K). Untargeted lipidomics based on high-performance liquid chromatography coupled to mass spectrometry (UHPLC-HRMS) was employed to obtain comprehensive information on whether relationships exist between these patient categories based on lipid patterns. In addition, malondialdehyde (MDA) as a standard marker of oxidative stress was monitored. The most characteristic lipids in group K were fatty acyls of hydroxyfatty acids (FAHFAs). As expected, MDA concentrations were the lowest in group K. Our findings can better explain ongoing pathologies, both acute and chronic, with the potential for future diagnosis and treatment.

Comparison of the Performance of the Leap Motion ControllerTM with a Standard Marker-Based Motion Capture System

Over the last few years, the Leap Motion Controller™ (LMC) has been increasingly used in clinical environments to track hand, wrist and forearm positions as an alternative to the gold-standard motion capture systems. Since the LMC is marker-less, portable, easy-to-use and low-cost, it is rapidly being adopted in healthcare services. This paper demonstrates the comparison of finger kinematic data between the LMC and a gold-standard marker-based motion capture system, Qualisys Track Manager (QTM). Both systems were time synchronised, and the participants performed abduction/adduction of the thumb and flexion/extension movements of all fingers. The LMC and QTM were compared in both static measuring finger segment lengths and dynamic flexion movements of all fingers. A Bland–Altman plot was used to demonstrate the performance of the LMC versus QTM with Pearson’s correlation (r) to demonstrate trends in the data. Only the proximal interphalangeal joint (PIP) joint of the middle and ring finger during flexion/extension demonstrated acceptable agreement (r = 0.9062; r = 0.8978), but with a high mean bias. In conclusion, the study shows that currently, the LMC is not suitable to replace gold-standard motion capture systems in clinical settings. Further studies should be conducted to validate the performance of the LMC as it is updated and upgraded.

Comparatives and Superlatives in the Romance Languages

Comparison expresses a relation involving two or more entities which are ordered on a scale with respect to a gradable property, called the parameter of comparison. In European languages, it is typically expressed through two constructions, comparatives and superlatives. Comparative constructions generally involve two entities, and indicate whether the compared entity shows a higher, lesser, or equal degree of the parameter with respect to the other entity, which is the standard of comparison. Superlatives set out one entity against a class of entities and indicate that the compared entity shows the highest or lowest degree of the parameter. Hence, comparatives may express either inequality (superiority or inferiority) or equality, whereas superlatives necessarily express superiority or inferiority. In traditional grammar, the terms comparative and superlative are primarily used to refer to the morphology of adjectives and adverbs in languages with synthetic marking (cf. Eng. slow, slower, slowest). However, while Latin has such synthetic marking, modern Romance languages no longer possess productive comparative or superlative suffixes. All Romance languages use analytic markers consisting of dedicated adverbs (e.g., Fr. plus ‘more’, moins ‘less’, aussi ‘as, also’) and determiners (e.g., Sp./It. tanto, Ro. atât ‘so much’). Superlatives are marked with the same markers and are mainly distinguished from comparatives by their association with definiteness. Another difference between comparatives and superlatives lies in the complements they license. Comparatives license a comparative complement, which may be clausal or phrasal, and which identifies the standard of comparison. As for superlatives, they license partitive PPs denoting the comparison set, which may be further specified by other PPs, a relative clause, or an infinitive clause. The Romance languages show many similarities with respect to the morphosyntactic encoding of comparatives and superlatives, but they also display important cross-linguistic differences. These differences may be related to the status of the comparative marker, the encoding of the standard marker, ellipsis phenomena in the comparative clause, and the dependence of the superlative on the definite article.

Phlebotomus (Adlerius) simici NITZULESCU, 1931: first record in Austria and phylogenetic relationship with other Adlerius species

Background: Phlebotomine sand flies are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). Sand fly findings in Central Europe are scarce and in Austria, to date only Phlebotomus mascittii has been recorded. In 2018 and 2019, entomological surveys were conducted in Austria with the aim to further clarify sand fly distribution and species composition.Results: In 2019, a Ph. simici specimen was trapped in Austria for the first time. Analyses of two commonly used marker genes, coxI and cytb, revealed high sequence identity with Ph. simici specimens from North Macedonia and Greece. Phylogenetic analyses showed high intraspecific distances within Ph. simici, thereby dividing this species into three lineages, from Europe, Turkey and Israel, respectively. Low interspecific distances between Ph. simici, Ph. brevis and a yet unidentified Adlerius sp. from Turkey and Armenia highlights that molecular identification can be challenging within the Adlerius complex, even when applying standard marker genes.Conclusion: This study provides the first finding of Ph. simici in Austria and the northernmost record so far. Moreover, it reveals valuable insights into the phylogenetic relationships of species within the Adlerius subgenus. Ph. simici is a suspected vector of Leishmania infantum and therefore of medical and veterinary importance. Potential sand fly expansion in Central Europe due to climatic change and the increasing import of Leishmania-infected dogs from endemic areas, urge the need for further studies on sand fly distribution in Austria and Central Europe in general.

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A.

Objectives To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. Methods SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. Results We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P&lt;0.001 and r = 0.664; P&lt;0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039). Conclusion ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

Phlebotomus (Adlerius) Simici Nitzulescu, 1931: First Record in Austria and Phylogenetic Relationship With Other Adlerius Species

Background Phlebotomine sand flies are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). Sand fly findings in Central Europe are scarce and in Austria, to date only Phlebotomus mascittii has been recorded. In 2018 and 2019, entomological surveys were conducted in Austria with the aim to further clarify sand fly distribution and species composition. Results In 2019, a Ph. simici specimen was trapped in Austria for the first time. Analyses of two commonly used marker genes, COI and cyt b, revealed high sequence identity with Ph. simici specimens from North Macedonia and Greece. Phylogenetic analyses showed high intraspecific distances within Ph. simici, thereby dividing this species into three lineages, from Europe, Turkey and Israel, respectively. Low interspecific distances between Ph. simici, Ph. brevis and a yet unidentified Adlerius sp. from Turkey and Armenia highlights that molecular identification can be challenging within the Adlerius complex, even when applying standard marker genes. Conclusion This study provides the first finding of Ph. simici in Austria and the northernmost record so far. Moreover, it reveals valuable insights into the phylogenetic relationships of species within the Adlerius subgenus. Ph. simici is a suspected vector of Leishmania infantum and therefore of medical and veterinary importance. Potential sand fly expansion in Central Europe due to climatic change and the increasing import of Leishmania-infected dogs from endemic areas, urge the need for further studies on sand fly distribution in Austria and Central Europe in general.

Model-Based Roentgen Stereophotogrammetric Analysis to Monitor the Head–Taper Junction in Total Hip Arthroplasty in Vivo—And They Do Move

Model-based Roentgen stereophotogrammetric analysis (RSA) using elementary geometrical shape (EGS) models allows migration measurement of implants without the necessity of additional attached implant markers. The aims of this study were: (i) to assess the possibility of measuring potential head–taper movement in THA in vivo using model-based RSA and (ii) to prove the validity of measured head–taper migration data in vitro and in vivo. From a previous RSA study with a 10 years follow-up, retrospectively for n = 45 patients head–taper migration was calculated as the relative migration between femoral ball head and taper of the femoral stem using model-based RSA. A head–taper migration of 0.026 mm/year can be detected with available RSA technology. In vitro validation showed a total migration of 268 ± 11 µm along the taper axis in a similar range to what has been reported using the RSA method. In vivo, a proof for interchangeable applicability of model-based RSA (EGS) and standard marker-based RSA methods was indicated by a significant deviation within the migration result after 12-month follow-up for all translation measurements, which was significantly correlated to the measured head–taper migration (r from 0.40 to 0.67; p < 0.05). The results identified that model-based RSA (EGS) could be used to detect head–taper migration in vivo and the measured movement could be validated in vitro and in vivo as well. Those findings supported the possibility of applying RSA for helping evaluate the head–taper corrosion related failure (trunnionosis).

Quantitative Analysis of Bioactive Phenanthrenes in Dioscorea batatas Decne Peel, a Discarded Biomass from Postharvest Processing

Dioscorea batatas Decne (Chinese yam) has been widely cultivated in East Asia for the purposes of food and medicinal uses for centuries. Along with its high nutritional value, the medicinal value of D. batatas has been extensively investigated in association with phytochemicals such as allantoin, flavonoids, saponins and phenanthrenes. Phenanthrenes are especially considered the standard marker chemicals of the Chinese yam for their potent bioactivity and availability of analysis with conventional high performance liquid chromatography with ultraviolet detection (HPLC-UV) methods. In order to investigate how much the contents of phenanthrenes are in the actual food products provided for consumers, D. batatas tuber was peeled and separated into its peel and flesh as in the conventional processing method. A quantitative analysis using the HPLC-UV method revealed that phenanthrenes are concentrically present in the D. batatas peel, while phenanthrenes are present in the flesh under the limit of detection. The difference in the contents of phenanthrenes is estimated to have arisen the considerable difference of antioxidant potential between the peel and the flesh. The results from this study suggest the high value of the discarded biomass of the Chinese yam peel and the necessity for the utilization of the Chinese yam peel.