Quality of life measurement in skin cancer patients: literature review and position paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes,Melanoma and Non‐Melanoma Skin Cancer

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient Oriented Outcomes, Melanoma and Non‐Melanoma Skin Cancer (NMSC) present a review of the literature and position statement on health‐related (HR) QoL assessment in skin cancer patients. A literature search was carried out to identify publications since 1980 that included information about the impact of SC on QoL. Generic, dermatology‐specific, cancer‐specific, SC‐specific, facial SC‐specific, NMSC‐specific, basal cell carcinoma‐specific and melanoma‐specific QoL questionnaires have been used to assess HRQoL in SC patients. HRQoL was assessed in the context of creation and validation of the HRQoL instruments, clinical trials, comparison of QoL in SC and other cancers, other diseases or controls, HRQoL assessment after treatment, comorbidities, behaviour modification, predictors of QoL and survival, supportive care needs, coping strategies and fear of cancer recurrence. The most widely used instruments for HRQoL assessment in SC patients are the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ‐C30), the Functional Assessment of Cancer Therapy‐Melanoma (FACT‐M), Skin Cancer Index (SCI), Short Form 36 Item Health Survey (SF‐36) and the Dermatology Life Quality Index (DLQI). The TFs recommend the use of the cancer‐specific EORTC QLQ‐C30, especially in late stages of disease, and the melanoma‐specific FACT‐M and SC‐specific SCI questionnaires. These instruments have been well validated and used in several studies. Other HRQoL instruments, also with good basic validation, are not currently recommended because the experience of their use is too limited. Dermatology‐specific HRQoL instruments can be used to assess the impact of skin‐related problems in SC. The TFs encourage further studies to validate HRQoL instruments for use in different stages of SC, in order to allow more detailed practical recommendations on HRQoL assessment in SC.     

Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.     

Inter‐serotype reassortment among epizootic haemorrhagic disease viruses in the United States

First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year.     

Effects of Pistacia atlantica on Oxidative Stress Markers and Antioxidant Enzymes Expression in Diabetic Rats

Introduction: Diabetes mellitus (DM) affects many patients all over the world. It involves different parts of the body, such as brain, eyes, kidneys, vessels, and so on. The lack of balance between free radicals and antioxidants is a possible mechanism involved in the pathogenesis of diabetes. Antioxidant treatment, especially natural forms, can be a beneficial solution. Therefore, we evaluated the effects of Pistacia atlantica oleoresin (PAO) on oxidative stress markers and antioxidant enzymes expression in diabetic rats.

Method: Fifty adult male Wistar rats were allotted randomly into five groups as follow: control group, diabetic control group, glibenclamide control group, diabetic glibenclamide group, diabetic treated group with 200?mg/kg PAO. Then PAO was prepared and analyzed by gas chromatography/mass spectroscopy (GC/MS). LD50 was also estimated for essential oil. Oxidative stress markers and antioxidant enzyme including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were also measured. The expression of GPx, CAT, and SOD genes was investigated using real-time polymerase chain reaction (PCR).

Results: The main constituents of essential oil gum were beta-pinene (29.38%), followed by alpha-pinene (18.15%), myrcene (7.36%), trans-pinocarveol (7.15%), and camphene (4.12%). Diabetes induced an increased level of MDA (69.92?±?3.92 vs. 43.76?±?3.73) and decreased levels of GSH (2.57?±?0.40 vs. 7.05?±?1.59), GPx (11.66?±?2.2 vs. 16.38?±?2.1), CAT (12.17?±?3.38 vs. 18.7?±?2.66), and SOD (0.78?±?0.67 vs. 2.41?±?0.46). In contrast, PAO treatment significantly decreased MDA (54.59?±?12.54 vs. 69.92?±?3.92) and increased GSH (4.5?±?0.89 vs. 2.57?±?0.40), GPx (25.86?±?5.37 vs. 11.66?±?2.2), CAT (22.69?±?0.36 vs. 12.17?±?3.38), and SOD (3.65?±?1.08 vs. 0.78?±?0.67) (p?<?0.05). Moreover, our results indicated that both GPx and CAT mRNA levels significantly increased approximately 4.46 and 6.23 times in rats fed with 200?mg/kg of PAO, more than that of the healthy control group, respectively (p?<?0.01 and p?<?0.001, respectively). Also, the average expression level of SOD was also significantly 1.57 higher in rats fed with 200?mg/kg of PAO in comparison to the diabetic control group (p?<?0.05).

Conclusion: The results indicated that PAO could be propose as an agent that protects the body against diseases that are associated with oxidative stress.     

Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

The succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.