Background During the 2018 WNV transmission season, similarly to other endemic areas in Europe, a large number of human West Nile virus (WNV) infections were reported in Hungary. Aims We summarise the epidemiological and laboratory findings of the 2018 transmission season and expand experiences in flavivirus differential diagnostics. Methods Every patient with clinical suspicion of acute WNV infection was in parallel tested for WNV, tick-borne encephalitis virus and Usutu virus (USUV) by serological methods. Sera, whole blood and urine samples were also tested for the presence of viral nucleic acid. Results Until the end of December 2018, 215 locally acquired and 10 imported human WNV infections were notified in Hungary. All reported cases were symptomatic; most of them exhibited neurological symptoms. In a large proportion of tested individuals, whole blood was the most appropriate sample type for viral nucleic acid detection, but because whole blood samples were not always available, testing of urine samples also extended diagnostic possibilities. In addition, the first human USUV infection was confirmed in 2018 in a patient with aseptic meningitis. Serological cross-reactions with WNV in different serological assays were experienced, but subsequent molecular biological testing and sequence analysis identified Europe lineage 2 USUV infection. Conclusion Careful interpretation and simultaneous application of different laboratory methods are necessary to avoid misdiagnosis of human USUV cases. Expansion of the laboratory-confirmed case definition criteria for detection of viral RNA in any clinical specimens to include urine samples could increase diagnostic sensitivity.

In this study we investigate the disease etiology in 12 patients with de novo variants in FAR1 all resulting in an amino acid change at position 480 (p.Arg480Cys/His/Leu). METHODS: Following next-generation sequencing and clinical phenotyping, functional characterization was performed in patients' fibroblasts using FAR1 enzyme analysis, FAR1 immunoblotting/immunofluorescence, and lipidomics. RESULTS: All patients had spastic paraparesis and bilateral congenital/juvenile cataracts, in most combined with speech and gross motor developmental delay and truncal hypotonia. FAR1 deficiency caused by biallelic variants results in defective ether lipid synthesis and plasmalogen deficiency. In contrast, patients' fibroblasts with the de novo FAR1 variants showed elevated plasmalogen levels. Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogendependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production. CONCLUSION: Heterozygous de novo variants affecting the Arg480 residue of FAR1 lead to an autosomal dominant disorder with a different disease mechanism than that of recessive FAR1 deficiency and a diametrically opposed biochemical phenotype. Our findings show that for patients with spastic paraparesis and bilateral cataracts, FAR1 should be considered as a candidate gene and added to gene panels for hereditary spastic paraplegia, cerebral palsy, and juvenile cataracts.

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Throughout the natural history of Parkinson's Disease (PD), from the pre-diagnostic phase to end stage disease, neuropsychiatric manifestations represent a core feature of the disease. This review summarises current knowledge on the features of depression, anxiety, apathy, fatigue, impulse control disorders (ICDs) and psychosis in PD. These co-morbidities are common and still frequently under-recognised. Their impact on quality of life is considerable, with depression having been shown to be the main determinant of health-related quality of life in PD patients. As well as formal diagnostic criteria, multiple scales have been developed to allow for assessment of these symptoms in both the clinic and research settings. The evidence base for treatment is variable, with increasing evidence for pharmacological and non-pharmacological treatment options for depression, but less robust evidence for the treatment of other neuropsychiatric features. Imaging studies are increasingly providing insight into the neural basis of these symptoms, with the hope that this insight will translate into treatments that can benefit patients.

Background Inflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a “tunneled” course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque. Methods and Results Maximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate‐high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate‐high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia‐inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192‐5P, 518D‐3P, and 532‐5P were upregulated in proximal EAT, whereas miR 630, 575, 16‐5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192‐5P, 518D‐3P, and 532‐5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PCG1a), adipogenesis, and angiogenesis genes. Conclusions Inflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia‐inducible factor 1a and/or miRNAs in an “inside‐to‐out” relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.