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Magnetic hyperthermia has received much attention during the last decade due to its implementation in cancer treatment. Recently, functionalized superparamagnetic iron oxide nanoparticles (SPION) emerged as a strong alternative adjuvant treatment approach, which complements conventional methods such as chemotherapy. In this study, we demonstrate the anticancer effect of Poly(acrylic acid)-coated, anti-HER2-tagged SPIONs on breast cancer cells using a low magnetic field strength of 0.8 kAm(-1), which is significantly lower compared to the literature, with a frequency of 400 kHz. Specificity was achieved via anti-HER2 antibody attachment to nanoparticles. HER2-positive SKBR3 and MDA-MB-453 cell lines internalized the nanoparticles successfully. These nanoparticles, which were not toxic to these cell lines, led to a prominent decrease in cell proliferation and survival in MDA-MB-453 cells when subjected to hyperthermia. Therefore, the hyperthermia-targeted SPION approach could be developed as a potential cancer treatment approach against breast cancer and possible other cancer types.

WOS: 000418389700017, PubMed ID: 29205472, Objective3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. MethodsThis multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. ResultsSixty-seven individuals (39 previously unreported) from 59 families were included (age range=5 days-33.4 years, median age=9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset=15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic putaminal eye was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. InterpretationMEGDHEL syndrome is a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004-1015, Else Kroner-Fresenius Stiftung; German Bundesministerium fur Bildung und Forschung (BMBF)Federal Ministry of Education & Research (BMBF); Horizon2020 through the E-Rare project GENOMIT [01GM1603, 01GM1207, FWF I 2741-B26]; Vereinigung zur Forderung Padiatrischer Forschung und Fortbildung Salzburg; Wellcome Centre for Mitochondrial Research [203105/Z/16/Z]; Medical Research Council (MRC) Centre for Translational Research in Neuromuscular Disease, Mitochondrial Disease Patient Cohort (UK)Medical Research Council UK (MRC) [G0800674]; Lily Foundation; UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, M.S. was supported by the Else Kroner-Fresenius Stiftung" This study was supported by the German Bundesministerium fur Bildung und Forschung (BMBF) and Horizon2020 through the E-Rare project GENOMIT (01GM1603 and 01GM1207 for HP and FWF I 2741-B26 for J.A.M. J.A.M., S.B.W., W.S. were supported by the Vereinigung zur Forderung Padiatrischer Forschung und Fortbildung Salzburg. R.W.T. was supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), the Medical Research Council (MRC) Centre for Translational Research in Neuromuscular Disease, Mitochondrial Disease Patient Cohort (UK) (G0800674), the Lily Foundation and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children.

Peroxisomal disorders are a group of genetically heterogeneous metabolic diseases related to dysfunction of peroxisomes. Dysmorphic features, neurological abnormalities, and hepatic dysfunction can be presenting signs of peroxisomal disorders. Here we presented dysmorphic facial features and other clinical characteristics in two patients with PEX1 gene mutation. Follow-up periods were 3.5 years and 1 year in the patients. Case I was one-year-old girl that presented with neurodevelopmental delay, hepatomegaly, bilateral hearing loss, and visual problems. Ophthalmologic examination suggested septooptic dysplasia. Cranial magnetic resonance imaging (MRI) showed nonspecific gliosis at subcortical and periventricular deep white matter. Case II was 2.5-year-old girl referred for investigation of global developmental delay and elevated liver enzymes. Ophthalmologic examination findings were consistent with bilateral nystagmus and retinitis pigmentosa. Cranial MRI was normal. Dysmorphic facial features including broad nasal root, low set ears, downward slanting eyes, downward slanting eyebrows, and epichantal folds were common findings in two patients. Molecular genetic analysis indicated homozygous novel IVS1-2A>G mutation in Case I and homozygous p.G843D (c.2528G>A) mutation in Case II in the PEX1 gene. Clinical findings and developmental prognosis vary in PEX1 gene mutation. Kabuki-like phenotype associated with liver pathology may indicate Zellweger spectrum disorders (ZSD).

The characteristics, perceptions, attitudes and behaviour of beach users at three locations: St George's Bay, Malta, Mamaia, Romania and Olu Deniz, Turkey, were determined from questionnaire surveys. Respondents comprised locals, domestic and foreign tourists. Results for these parameters had substantial agreement both across the three beaches and with previous studies. The amounts beach users were willing to pay (WTP), via the contingent valuation method and their consumer surpluses (CS), via the travel cost method were determined. The average amount beach users were willing to pay per visit, was £0.64 on St George's bay, £0.32 on Mamaia and £0.94 on Olu Deniz. The willingness to pay varied with social class, earnings, amount of beach use and between local, domestic and foreign user groups. The consumer surplus also varied for these groups as British tourists had a CS of £0.62 per visit, with domestic Turkish and Romanian users having values of £0.46 and £0.69, respectively. Diminishing marginal utility, as measured by WTP, with beach use was found in all three surveys. Charging for actual use would be acceptable for the majority of beach users. Coastal zone managers could realise significant revenues from beach users if they charge adults on a per visit basis (the favoured mode of payment) and spend the revenue on the maintenance and improvements identified by the users. Only one of the beaches (Olu Deniz, Turkey) currently has restricted access, which would facilitate such a payment method., peer-reviewed

Association of 3-methylglutaconic aciduria with impaired oxidative phosphorylation, deafness, encephalopathy, leigh-like lesions on brain imaging, progressive spasticity and dystonia defined as a distinct entity under the name of MEGDEL syndrome. It is an autosomal recessive disorder due to mutation in the serine active site-containing protein 1 (SERAC1). SERAC1 is localized at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. It was identified as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. Here we report two new Turkish sibling patients affected with MEGDEL syndrome due to SERAC1 gene mutation. The patients were presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures, basal ganglia involvement. Metabolic acidosis, mild hyperammonemia and lactic acidemia were accompanied with clinical findings in newborn period.