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Plasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological mechanisms underlying brain aging while concomitantly supporting cognitive preservation. In this study we analyzed plasma Alzheimer's disease (AD) core biomarkers, neurofilament light chain (NfL), and glial fibrillary acid protein (GFAP) using the Single Molecule Array (SIMOA) platform in 75 cognitively preserved nonagenarians, and compared with baseline samples of 153 volunteers who were cognitively unimpaired (CU) during six years (classified in ≤ 70, and 71 to 85 years of age), and with 108 AD patients. Nonagenarians almost lack the APOEε4 allele, and had significantly higher Aß40, Aß42, p-tau181, NfL, and GFAP, along with a significantly lower Aß42/40 ratio (P&;lt0.001) compared with the two CU groups. NfL and GFAP tripled concentrations in nonagenarians. No differences were noted in any plasma biomarker between the younger and older CU groups. Biomarkers correlated strongly with age only when analyzing together CU controls and nonagenarians. Compared with AD cases, nonagenarians showed lower p-tau181 (P=0.001), higher total tau (P=0.02), and much higher Aß40, Aß42 and NfL levels (P&;lt0.001). The levels of GFAP in nonagenarians were similar to those observed in AD patients. In conclusion, cognitively preserved nonagenarians do not develop the AD biomarker signature and exhibit higher levels of Aß42. However, their threefold increase in NfL and GFAP supports their aging brains are somehow resilient to neurodegeneration. These data support caution in the prognosis of clinical dementia based on NfL and GFAP values. Overall, plasma biomarkers in CU individuals remained quite stable till the eighties.

The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.

Gnomoniopsis smithogilvyi (Gnomoniaceae, Diaporthales) is the main causal agent of chestnut brown rot on sweet chestnut worldwide. The rotting of nuts leads to alterations in the organoleptic qualities and decreased fruit production, resulting in significant economic losses. In 2021, there was an important outbreak of chestnut rot in southern Galicia (Spanish northwest). The profile of secondary metabolites from G. smithogilvyi was studied, especially to determine its capability for producing mycotoxins, as happens with other rotting fungi, due to the possible consequences on the safety of chestnut consumption. Secondary metabolites produced by isolates of G. smithogilvyi growing in potato dextrose agar (PDA) medium were identified using liquid chromatography coupled with high-resolution mass spectrometry. Three metabolites with interesting pharmacological and phyto-toxicological properties were identified based on their exact mass and fragmentation patterns, namely adenosine, oxasetin, and phytosphingosine. The capacity of G. smithogilvyi to produce adenosine in PDA cultures was assessed, finding concentrations ranging from 176 to 834 µg/kg. Similarly, the production of mycotoxins was ruled out, indicating that the consumption of chestnuts with necrotic lesions does not pose a health risk to the consumer in terms of mycotoxins., (© 2024. The Author(s).)

Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations., Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data., Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers., Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD., (© 2024. The Author(s).)

Introduction: Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies., Methods: We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate., Results: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism., Discussion: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases., Highlights: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3'UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.

About 60% of the nut production of sweet chestnut ( Castanea sativa Mill.) in Europe originates in Spain (FAOSTAT, 2022), mostly (91%) in Galicia (NW Spain). In September 2021, premature fall of immature chestnut burrs and nuts of C. sativa was observed in eight orchards of Pontevedra and Ourense (provinces of Galicia). Chestnut green burrs had turned brown and fallen off, and the nuts showed brown lesions in kernels and embryos. Some nuts had become mummified. Symptomatic samples of burrs and nuts, including mummified fruits, were collected. Small pieces of samples were surface-disinfected with 2% sodium hypochlorite, and plated onto potato dextrose agar (PDA) plates. Colonies were creamy white to gray or light brown, and presented a woolly to felty mycelium with a dense development in concentric circles. Brownish to black conidiomata, produced abundantly, were globose to sub-globose. Conidia were hyaline, oval, obovoid, fusoid and multi-guttulate, and 6.6±0.78 [5.07 to 9.01] μm x 3.2±0.43 [2.41 to 4.38] μm in size. These features matched those described for Gnomoniopsis smithogilvyi (Shuttleworth et al. 2012), syn. G. castaneae (Visentin et al. 2012; Shuttleworth et al. 2015). Genomic DNA was extracted from mycelium developed in 22 burrs and nuts, and 30 pure cultures. The rDNA internal transcribed spacer (ITS), fragments of the β-tubulin (TUB2) and the translation elongation factor-1α (TEF-1α) genes were amplified using ITS1F (Gardes and Bruns 1993) and ITS4 (White et al. 1990), T1/Bt2b (O'Donnell and Cigelnik 1997), and EF1-728F/EF1-986R (Carbone and Kohn 1999) primers, respectively. Two isolates (EFA 924A, EFA962.4A) were deposited in the Spanish Type Culture Collection (Paterna, Valencia), and their sequences submitted to GenBank (accession nos.: ITS: OM319846, OM319848; TUB2: OM417078, OM417080; TEF-1α: OM417081, OM417083). BLASTn analyses showed: for ITS and TEF-1α sequences, ≥99.7% identity to the ex-type of G. smithogilvyi (ITS: JQ910642, 474 matching bp; TEF-1α: JQ910645, 335-338 matching bp), and for TUB2 sequences, ≥99.1% identity to G. castaneae (LN999975, 446-453 matching bp). Pathogenicity tests were carried out on surface disinfected nuts of Castanea sativa `Raigona´. A superficial wound was made in the pericarp of each nut. A 2-mm mycelial plug of a 7-days-old culture of G. smithogilvyi was then inoculated: twenty nuts with isolate EFA924A and twenty with isolate EFA962.4A. Twenty nuts inoculated with sterile agar were used as control. The holes were sealed with Parafilm®. Nuts were incubated in a moist chamber at 22±2°C. Two replicated tests were carried out. Four inoculated and four control nuts were inspected for the presence and progress of rot symptoms every seven days. Three weeks after inoculation, all remaining inoculated nuts were completely rotted, whereas all control nuts remained healthy. Gnomoniopsis smitholgilvyi was reisolated from all inoculated nuts, and it was not recovered from the controls. This pathogen causes chestnut brown rot on sweet chestnut worldwide (EPPO, 2022), causing also shoot cankers on chestnut (Lione et al, 2019). This is the first report of G. smithogilvyi causing chestnut brown rot on nuts and burrs of C. sativa in Spain. Future studies on the incidence of this pathogen and its impact on chestnut yield should be carried out in the main European producing countries, i.e. Spain, Italy, Portugal and Greece, where the disease has been detected and represents an emerging threat to chestnut production.

Maize and grass silages are important dietary components for ruminant livestock that influence the quality of animal products for human consumption, such as milk, in many parts of the world. Infection of plants by fungi able to produce mycotoxins, either in the field or post-harvest, can result in a decrease of silage nutritional quality and, consequently, in milk quality. In this study, 45 maize and grass silage samples were collected from 25 dairy farms located in the north of Portugal. The occurrence of fungi was evaluated in samples, the most frequently isolated species being Aspergillus fumigatus, Dipodascus geotrichum, Mucor circinelloides, Penicillium paneum, and Aspergillus flavus. The mycotoxigenic profile of the fungal species was studied using the ultra-high-performance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UHPLC-MS-IT-TOF) detection. In addition, a new method based on a QuEChERS extraction followed by the UHPLC- tandem mass spectrometry (UHPLC-MS/MS) detection was developed for simultaneous analysis of 39 mycotoxins in silage. A high co-occurrence of Fusarium mycotoxins was found, although at low levels of contamination. Deoxynivalenol and beauvericin were found in more than 82% of maize silage samples. It can be highlighted the low occurrence of Penicillium and Aspergillus toxins in the maize and grass silages studied despite the frequent detection of species of both genera., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

A simple method for the quantification of 40 mycotoxins in milk was developed. This method is based on a QuEChERS extraction followed by the ultra-high liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection, and allows the simultaneous analysis of regulated, emerging, and modified mycotoxins. A sample treatment procedure was optimized to include a concentration step for the analysis of some compounds such as aflatoxin M 1 . The method was in-house validated in terms of limits of detection (LODs), limits of quantification (LOQs), linearity, recoveries, and precision. LOQs lower than 10 ng/mL were obtained, and recoveries ranged from 61% to 120% with a precision, expressed as the relative standard deviation, lower than 15%. Therefore, acceptable performance characteristics were obtained fulfilling European regulations. The method was successfully applied for the quantification of mycotoxins in raw milk. It can be highlighted high occurrence of beauvericin and enniatins were found in low amounts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive., Methods: Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPβ peptides. We evaluate variant's pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort., Results: The mutation was absent from public databases and segregated with the disease. CSF Aβ42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPβ levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPβ levels resembled those of controls. Therefore, a decreased sAPPα/sAPPβ ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened., Conclusions: This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers.

Marine and freshwater toxins contaminate water resources, shellfish and aquaculture products, causing a broad range of toxic effects in humans and animals. Different core-shell nanoparticles were tested as a new sorbent for removing marine and freshwater toxins from liquid media. Water solutions were contaminated with 20 μg/L of marine toxins and up to 50 μg/L of freshwater toxins and subsequently treated with 250 or 125 mg/L of nanoparticles. Under these conditions, carbon nanoparticles removed around 70% of saxitoxins, spirolides, and azaspiracids, and up to 38% of diarrheic shellfish poisoning toxins. In the case of freshwater toxins, the 85% of microcystin LR was eliminated; other cyclic peptide toxins were also removed in a high percentage. Marine toxins were adsorbed in the first 5 min of contact, while for freshwater toxins it was necessary 60 min to reach the maximum adsorption. Toxins were recovered by extraction from nanoparticles with different solvents. Gymnodinium catenatum, Prorocentrum lima, and Microcystis aeruginosa cultures were employed to test the ability of nanoparticles to adsorb toxins in a real environment, and the same efficacy to remove toxins was observed in these conditions. These results suggest the possibility of using the nanotechnology in the treatment of contaminated water or in chemical analysis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Mycotoxins are toxic compounds that can be present in feed, food and beverages. In this work, 25 magnetic nanostructured materials were developed to remove the main types of mycotoxins from liquid food matrices. The efficiency for binding mycotoxins from contaminated aqueous solutions was studied. Nanocomposites (diameters lower to 15 μm) composed of mixtures of activated carbon, bentonite and aluminium oxide were able to eliminate up to 87% of mycotoxins with an adsorption efficiency of 450 µg/g. On the other hand, spheres with sizes below 3 mm and composed by biopolymers and activated carbon or graphene oxide removed up to 70% of mycotoxins (adsorption of 598 ng/g). These particles were tested for beer detoxification, and spheres composed of alginate and activated carbon or pectin maintain the ability to eliminate toxins from this beverage. Hence, this technology could be a useful tool for the food industry., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fusarium foetens, a pathogen of Begonia plants, has been recently described as a new fungal species. This Fusarium species causes a destructive vascular wilt disease which leads to the death of the plant. Moreover, Fusarium species are known to produce a huge variety of secondary metabolites such as mycotoxins and phytotoxins. Here, we studied the toxicogenic profile of one F. foetens strain, isolated from maize, employing two methods based on the use of ultra-performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight detection. The mycotoxins beauvericin and fusaric acid were detected in a pure culture of F. foetens. In addition, four fusaric acid analogs (10,11-dihidroxyfusaric acid, hydroxyfusaric acid, dehydrofusaric acid, and a hydroxylated unsaturated fusaric acid analog) were tentatively identified on the basis of their accurate mass and fragmentation patterns. Therefore, these preliminary data indicate that F. foetens isolated from maize is able to produce Fusarium mycotoxins including beauvericin and fusaric acid.

Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy. Astrocytic tauopathy, 4R(+) and 3R(-) immunoreactive, was characterized by thorn-shaped astrocytes present in subpial, subependymal, and perivascular areas, and in gray matter; plus granular or fuzzy tau immunoreactivity in astrocytic processes in gray matter, either solitary or clustered in different regions. Some neurofibrillary tangles and pretangles, both 3R and 4R(+), were present in the medial temporal lobe but did not exhibit the characteristic distribution of Alzheimer's type pathology. This 4R-tau aging-related tau astrogliopathy is likely a co-occurring pathology, although an interaction between progranulin and tau proteins within the neurodegenerative process should not be ruled out., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A new method based on a QuEChERS extraction followed by the ultra-high liquid chromatography tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the analysis of mycotoxin in beer. The method allows the identification and quantification of 23 mycotoxins with different chemical characteristic including regulated, emerging and masked compounds. A sample treatment procedure involving a QuEChERS extraction and dispersive solid-phase clean-up steps was applied. This protocol involves a new approach based on a sample concentration before the extraction. The method was in-house validated in terms of limits of detection (LODs), limits of quantification (LOQs), linearity, repeatability and recoveries. For most compounds, recoveries ranged from 70% to 110% with LOQs (from 0.038 to 30.43 µg/L) lower than the maximum residue levels established in European regulations. In general, acceptable performance characteristics were obtained fulfilling the current legislation. Therefore, the proposed method is appropriate for routine analysis of beer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mycotoxins occur naturally as agricultural contaminants all over the world. The toxic effects of some of their metabolites are known and their presence regulated in food and feed. This paper describes two methods for the detection of toxins of type-A trichothecenes group, and their modified forms, using mass spectrometry. Ultra-performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight (UPLC-MS-IT-TOF) was employed to characterize the fragmentation pathways of 10 type-A trichothecenes, and characteristic ions were tentatively identified in scan mode through their accurate masses. Unknown signals were detected in a F. sporotrichioides extract, which afterwards were identified as seven modified forms of neosolaniol (NEO) and T-2 toxin. Then, UPLC coupled to tandem mass spectrometry (MS/MS) was employed to develop a precursor ion scanning method that can be used as a screening tool to detect any modified type-A trichothecenes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.

A method based on the combined use of ultraperformance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UPLC-MS-IT-TOF) detection was employed to identify the metabolite production of Aspergillus ochraceus, which is the major cause of food and feed contamination due to ochratoxin A. Under the proposed chromatographic conditions, seven metabolites belonging to the family of circumdatins were separated and identified. Their initial identification was performed through the exact molecular formula, as a function of their accurate mass. Collision-induced dissociation was applied to predict precursor and product ions, and the elemental composition of each compound was obtained. The elimination of nitrogenous groups followed by successive losses of carbonyl groups is the common fragmentation pathway of circumdatins. With the fragmentation data obtained, an UPLC-MS/MS method was created and optimized to detect circumdatins in corn samples.

For diagnostic purposes, we screened for the C9ORF72 mutation in a) 162 FTLD cases, and b) 145 cases with other diagnoses but with some frontotemporal features or manifestations previously reported in C9 carriers. Ten cases (onset 50 to 75 years) harbored the expansion: seven had FTLD syndromes (4.3% of total, 11% of familial cases), and three (2%) had a different diagnosis. All positive cases had family history of dementia, psychiatric disease, or ALS, but only 20% of families with mixed FTLD/ALS phenotypes carried the expansion. Language impairment was the most common symptom, followed by behavioral changes, memory deficits, and parkinsonism. C9ORF72 mutation has a low frequency in our dementia series and very diverse clinical manifestations.

Background: Patients with primary progressive aphasia (PPA) usually develop significant behavioral disturbances with progression of the disease. We tested our clinical observation that development of disruptive agitation is more likely in semantic than in nonfluent PPA and examined which clinical variables could be associated with this behavior., Methods: We retrospectively analyzed neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n = 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical variables and laterality of temporal atrophy were associated with symptoms in semantic PPA cases., Results: The semantic PPA group developed more frequent (p = 0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly associated with psychotic symptoms (delusions/hallucinations) but was not associated with gender, age at onset, duration of the disease, or laterality of temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed and treated with antidepressants (p = 0.0007). There were no differences in anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor behavior., Conclusions: Semantic PPA in advanced disease is frequently associated with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent PPA maintains a high prevalence of depression. This implies different treatment and care and support needs for each group., (© 2015 S. Karger AG, Basel.)

Aims: Bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae (Psa) is currently the major threat to its commercial production worldwide. In 2011, the most virulent type (Psa3) was detected for the first time in Northwest-Spain, in the province of Pontevedra. In 2013 surveys, leaves and flower buds with mild symptoms were observed in Actinidia deliciosa 'Hayward' vines in an orchard at the province of A Coruña, suggesting the presence of P. syringae pv. actinidifoliorum (Psaf)., Methods and Results: Isolates obtained from such orchard were characterized by morphological, biochemical and physiological tests, fatty acids (FA) profile and molecular tests (PCR, BOX-PCR, duplex PCR, multiplex PCR, real-time PCR, PCR-C, phytotoxins, housekeeping and effector genes). Pathogenicity tests were also carried out on plants and fruits of A. deliciosa 'Hayward' and on different cultivated plants and fruits. Results demonstrated the presence of P. syringae pv. actinidifoliorum in Spain., Conclusions: The work provides new information on the pathovar P. syringae pv. actinidifoliorum, which has only been found previously in New Zealand, Australia and France., Significance and Impact of Study: The results are relevant for taxonomy of isolates of P. syringae from kiwifruit, especially those of low virulence not belonging to pathovar actinidiae., (© 2015 The Society for Applied Microbiology.)

Background: In recent years, a benign variant of frontotemporal lobar degeneration (FTLD) has been recognized, with a particularly slow progression of cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in neuroimaging studies. Patients with FTLD have been considered "phenocopies," with an underlying nondegenerative neurologic process., Results: We report the first family with three affected members having benign FTLD associated with C9ORF72 gene hexanucleotide expansion. Onset of symptoms occurred during the fifth decade, with naming and memory problems as the main features. Two siblings have stabilized at mild cognitive impairment or incipient dementia for more than a decade, and remain quite independent for their activities of daily living at the current ages of 69 and 65 years, respectively. Their mother's cognitive deterioration evolved slowly during >30 years., Conclusion: This family demonstrates that a benign evolution can be part of the growing spectrum of clinical phenotypes associated with neurodegenerative diseases caused by the C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be considered in cases with this slow deterioration, especially if there is a family history., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Decreased plasma progranulin levels are a very specific marker for the diagnosis of frontotemporal lobar degeneration (FTLD) caused by mutations in the progranulin gene (GRN). A frequent neuroimaging pattern in this type of dementia is asymmetric cortical atrophy. The aim of this study was to screen for GRN-linked FTLD in cases with different cortical dementia phenotypes and asymmetric perisylvian atrophy., Methods: Progranulin plasma levels were analyzed in a variety of FTLD phenotypes (n = 71), dementia of the Alzheimer type (DAT) (n = 22) and probable Lewy body dementia (n = 8), both latter groups presented with asymmetric perisylvian atrophy. A group of elderly controls (n = 29) and DAT cases with symmetric atrophy (n = 33) were also analyzed. The GRN gene was sequenced in cases with lower plasma levels., Results: Four cases with clinical FTLD phenotypes and plasma levels below 70 ng/ml were found to carry different GRN mutations: M1?, C139R, a point mutation in the splice donor site of intron 3 (A89VfsX41), and a deletion in exon 9 (A303AfsX57), this latter one being a new mutation. Thirteen cases with levels between 72 and 85 ng/ml did not show pathogenic changes in the GRN gene. None of the cases with asymmetric atrophy and clinical phenotypes other than FTLD had GRN mutations., Conclusions: Asymmetric perisylvian atrophy is not likely to predict progranulin-linked FTLD unless it is associated with a consistent FTLD clinical phenotype., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Virgin oils obtained from seeds of Camellia oleifera (CO), Camellia reticulata (CR) and Camellia sasanqua (CS) were studied for their triacylglyceride composition, antioxidant and antimicrobial activities. Levels of fatty acids determined by ¹H-nuclear magnetic resonance analysis were similar to those reported for olive oils (82.30%-84.47%; 5.69%-7.78%; 0.26%-0.41% and 8.04%-11.2%, for oleic, linoleic, linolenic and saturated acids, respectively). The CR oil showed the best antioxidant potential in the three in vitro models tested. With regard to EC₅₀ values (µg/mL), the order in DPPH radical-scavenging was CR (33.48) < CO (35.20) < CS (54.87). Effectiveness in reducing power was CR (2.81) < CO (3.09) < CS (5.32). IC₅₀ for LPO inhibition were 0.37, 0.52 and 0.75 µg/mL for CR, CO and CS, respectively. All the oils showed antimicrobial activity, and exhibited different selectivity and MICs for each microorganism tested (E. coli, B. cereus and C. albicans). B. cereus was the less sensitive species (MIC: 52.083 ± 18.042 for CO; 41.667 ± 18.042 for CR; 104.167 ± 36.084 for CS mg/mL) and the E. coli was the most sensitive to camellia oil's effect. The standard gentamicin presented higher MIC for E. coli (4.2) than the CR (MIC= 2.6) and CO (MIC = 3.9) oils.

Background: : Finding variables that predict decline or stability in persons with amnestic mild cognitive impairment (aMCI) is an important step in identifying subjects in prodromal stages of dementia. This study tests a clinical observation suggesting that aMCI cases with better-preserved recognition skills, despite similar delayed recall deficits, are more likely to remain functionally stable., Methods: : A cohort of 210 cases with aMCI, diagnosed with standardized criteria that had been followed up for 48 ± 12 months (range: 36-100), were divided into two groups according to their initial recognition memory discrimination index (DI) on the Hopkins Verbal Learning Test (DI ≥ or <8). We compared the two groups according to demographic and neuropsychological variables, cerebral small vessel disease, and outcome (progression to dementia versus stability as aMCI)., Results: : Thirty-seven percent progressed to dementia. In the group with the higher DI scores (n = 107), only 21.5% of the cases converted, compared with 52.4% of lower scorers (n = 103; Fisher's test: p < 0.0001). Progression to dementia occurred significantly later in cases with higher DI (50 ± 17 versus 26 ± 11 months in cases with impaired DI, Mann-Whitney test, U statistic = 1092.5, p < 0.0001). The group with lower DI showed a threefold-increased rate of progression to dementia. A multivariate regression model revealed DI, delayed recall, age, and family history of dementia as the strongest predictors of dementia, in this order., Conclusions: : The aMCI patients with better-preserved recognition at baseline have a more benign prognosis. Detection of these cases may aid in isolating other aMCI cases that are already in prodromal stages of AD and in selecting more homogeneous groups for clinical trials.

Camellia japonica (CJ) has oil-rich seeds, but the study of these oils has received little attention and has mainly focused only on their health properties. In the present work the relative composition of the fatty acid (FA) components of the triglycerides in cold-pressed oil from CJ is studied by ¹H-NMR. The results obtained were: 75.75%, 6.0%, 0.17% and 18.67%, for oleic, linoleic, linolenic and saturated FA respectively. Levels of C₁₈ unsaturated FA found in CJ oil were similar to those reported for olive oils. We also checked the possibility of using ¹³C-NMR spectroscopy; however, the results confirmed the drawback of ¹³C over ¹H-NMR for the study of FA components of CJ triglycerides due to its low gyromagnetic ratio and its very low natural abundance.

We describe the clinical phenotype of nine kindred with presenile Alzheimer's disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare them with reported families with mutations in the same codons. Mutations were in exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7 (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser). Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not been previously reported. Distinct clinical features, including age of onset, symptoms and signs associated with the cortical-type dementia and aggressiveness of the disease, characterized the different mutations and were quite homogeneous across family members. Age of onset fell within a consistent range: some mutations caused the disease in the thirties (P117R, L226F, V272A), other in the forties (E120G, H163R, V261L, L282R), and other in the fifties (F105V, I439S). Associated features also segregated with specific mutations: early epileptic activity (E120G), spastic paraparesis (V261L), subcortical dementia and parkinsonism (V272A), early language impairment, frontal signs, and myoclonus (L226F), and late myoclonus and seizures (H163R, L282R). Neurological deterioration was particularly aggressive in PS1 mutations with earlier age of onset such as P117R, L226F, and E120G. With few exceptions, a similar clinical phenotype was found in families reported to have either the same mutation or different amino acid changes in the same codons. This series points to a strong influence of the specific genetic defect in the development of the clinical phenotype.

Background: Visual hallucinations are a core feature of dementia with Lewy bodies (DLB) and have been proposed as being part of a narcolepsy-like REM sleep disorder. Selective loss of hypothalamic hypocretin-producing neurons is common to both narcolepsy and the spectrum of Lewy body diseases. We hypothesized that the genetic marker associated with narcolepsy, the HLA class II DR2-DQ6 haplotype, could confer some degree of susceptibility to brainstem-hypothalamic damage leading to the manifestation of visual hallucinations., Methods: We examined HLA class II haplotypes in 30 patients with prominent visual hallucinations in the context of clinical criteria for DLB and in 30 patients affected by a cortical-type dementia without hallucinations., Results: No significant differences were found in the distribution of DR and DQ antigens., Conclusions: We conclude that hypothalamic vulnerability in different diseases is not mediated by a common HLA haplotype., (Copyright 2010 S. Karger AG, Basel.)

The effects of drying and pelletizing on the properties of broiler chicken litter, obtained from a farm in northwest Spain, were investigated. The drying and pelletizing process reduced among-batch variability in dry matter content, electrical conductivity, urea N, and K, S, Na, Fe, Cu and Cd contents, but increased among-batch variability in total N, ammonium N, nitrate N, total P and pH. N form contents in the pelletized product could be estimated with reasonable accuracy on the basis of dry matter content. Cr, Cu and Cd contents were all significantly lower in the dried pelletized product than in fresh litter, whereas Pb content was significantly higher. The dried pelletized product is of course clearly preferable to the fresh product as regards storage and handling, however, our results suggest a need to optimize the production process with the aim of reducing possible contamination during manufacture, and of minimizing variability in N form contents, P content and pH.

Background: Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects., Objective: To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD., Setting: Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain., Methods: Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype., Results: Maternal transmission of AD was significantly more frequent than paternal transmission (P < .001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (< or =5 years) or high (>5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO., Conclusions: There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

Armillaria mellea (Vahl ex Fr) Kummer is an aggressive pathogen which causes white root rot in a wide range of hosts. Most chemicals tested so far against Armillaria, both in vitro and in the field, have not been effective in reducing fungal growth and/or preventing plant decline and mortality. In the present work the effects of four DMI (sterol demethylation inhibitor) fungicides, cyproconazole, hexaconazole, propiconazole and tetraconazole, and another six downwardly mobile systemic chemicals, azoxystrobin, cubiet (copper bis(ethoxy-dihydroxy-diethylamino)sulfate), fosetyl-Al, potassium phosphite, sodium tetrathiocarbonate (STTC) and 2-(thiocyanomethylthio)benzothiazole (TCMTB), on the mycelial growth of A. mellea were compared and evaluated; the product yielding the best results in in vitro experiments was selected to determine its efficacy in preventing decline and mortality of grapevines in the field. Best results on in vitro fungal growth reduction were obtained with the four azoles tested, in particular with cyproconazole and hexaconazole, achieving 67-72% mycelial growth inhibition at the lowest dose. Results obtained in the field showed that a dose of 50 mg AI litre(-1) of cyproconazole once or twice a year was efficient in controlling the disease even in vines seriously affected by the pathogen. However, further research is required to study minimum effective doses, residual effects and the convenience of the application of annual dressings in damaged vineyards, so as to gradually reduce the pathogen inoculum potential in soil and control the disease while reducing chemical residues in the plant and preventing development of fungal resistance.

Background: Most patients with dementia with Lewy bodies (DLB) exhibit diffuse plaque-only pathology with rare neocortical neurofibrillary tangles (NFTs), as opposed to the widespread cortical neurofibrillary-tau involvement in Alzheimer disease (AD). Another pathological difference is the astrocytic and microglial inflammatory responses, including release of interleukins (ILs), around the neuritic plaques and NFTs in AD brains that are absent or much lower in DLB. We analyzed cerebrospinal fluid (CSF) markers that reflect the pathological differences between AD and DLB., Objective: To determine CSF concentrations of tau, beta-amyloid, IL-1beta, and IL-6 as potential diagnostic clues to distinguish between AD and DLB., Methods: We measured total tau, beta-amyloid1-42, IL-1beta, and IL-6 levels in CSF samples of 33 patients with probable AD without parkinsonism, 25 patients with all the core features of DLB, and 46 age-matched controls., Results: Patients with AD had significantly higher levels of tau protein than patients with DLB and controls (P<.001). The most efficient cutoff value provided 76% specificity to distinguish AD and DLB cases. Patients with AD and DLB had lower, but not significantly so, beta-amyloid levels than controls. The combination of tau and beta-amyloid levels provided the best sensitivity (84%) and specificity (79%) to differentiate AD vs controls but was worse than tau values alone in discriminating between AD and DLB. Beta-amyloid levels had the best correlation with disease progression in both AD and DLB (P =.01). There were no significant differences in IL-1beta levels among patients with AD, patients with DLB, and controls. Patients with AD and DLB showed slightly, but not significantly, higher IL-6 levels than controls., Conclusions: The tau levels in CSF may contribute to the clinical distinction between AD and DLB. Beta-amyloid CSF levels are similar in both dementia disorders and reflect disease progression better than tau levels. Interleukin CSF concentrations do not distinguish between AD and DLB.

Chronic alcoholic patients frequently exhibit a mild to moderate cognitive impairment that has been related to Wernicke-Korsakoff encephalopathy and attributed tentatively to nutritional and vitamin deficiencies. To elucidate the possible relation between alcoholic cognitive deterioration (ACD) and nutritional and vitamin deficiencies, several tests of intelligence and memory were administered to 54 chronic alcoholic patients and 30 controls. Serum levels of thiamine, folic acid, vitamins B12, A, and E, and certain nutritional indexes were determined in most of the subjects. The alcoholics scored significantly lower in intellectual and visuospatial tasks but not in verbal memory tasks. They had a lower serum level for thiamine but not of the remaining vitamins. However, the correlations between serum thiamin and cognitive performance scores were low, and according to stepwise regression analysis, duration of alcohol intake and education were the variables with predictive value for intellectual and memory test performance. These results suggest that serum thiamin deficiency is not the main pathogenetic factor related to ACD.