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Platelet-rich plasma (PRP) and botulinum toxin type A (BTX-A) injections have proven effective in clinical trials for plantar fasciitis treatment but have not been directly compared. We aimed to compare clinical outcomes in patients undergoing PRP or BTX-A injections. We performed a randomised controlled trial (59 patients; 1-year follow-up) to assess efficacy, using pain and functional scales (VAS, AOFAS Hindfoot-scale and FAAM questionnaire) and fascia thickness reduction, in control and single ultrasound-guided BTX-A or PRP injection groups. The BTX-A group showed better results at 1-month after treatment. Conversely, the PRP injection was more effective in the long-term, with significant pain reduction and functional improvement. Plantar fascia thickness significantly reduced from months 1 and 3 in the PRP and BTX-A groups, respectively. PRP and BTX-A injections are effective in patients with plantar fasciitis with BTX-A achieving better short-term pain reduction and PRP better long-term results. Level I; Randomised Controlled Trial [ABSTRACT FROM AUTHOR]

• High school teachers associate the languages of immigrant students with misbehavior. • Immigrant students' heritage languages get banned at Catalan high schools. • Discourse on integration in Catalan schools shows pressure towards assimilation. • Public displays of the heritage language make immigrant students appear "unintegrated". This study explores high-school teachers' discourse on heritage language use regarding their students of immigrant background in Catalonia, Spain, where both Catalan and Spanish are official languages. For this purpose, 10 high-school teachers from 5 schools with a high ratio of foreign students were interviewed. These interviews were analysed using membership categorization analysis. The results show that the perceived appropriateness of heritage language use depends on whether the students are integrated enough in the eyes of locals. Additionally, heritage language use in public is judged from the perspective of a Catalan listener and is deemed disrespectful. This is particularly salient in students of Moroccan background, where language maintenance is associated with overly strict adherence to Islam. The need for training teachers on how to properly address the linguistic and cultural diversity of their classrooms is discussed. [ABSTRACT FROM AUTHOR]

This study analyzes the influence of identity complexity on the linguistic acculturation expectations that Catalan high-school students hold towards their peers of Moroccan and Romanian origin. It also takes into account social status and cultural proximity, expecting higher expectations of linguistic integration towards Romanians. Using a 5-point Likert scale, 345 autochthonous high-school students were asked about their degree of self-identification with Spain and Catalonia. Then, they responded to several questions concerning linguistic acculturation expectations regarding Romanians and Moroccans. While integration is the most popular profile for all three groups, the bicultural identity group scored the highest, followed by the Catalan identity group and the Spanish identity group ranking last. Bicultural identification was also a significant predictor for all integration measures, as was Catalan identification for 'integration to Catalan' and 'integration to Spanish and Catalan'. However, the distinctions between answers regarding Romanians and Moroccans were scant. We conclude that incorporating the languages of immigration into a bilingual host society is not only possible, this type of community may even be more welcoming. The potential of working with the concept of identity complexity to decrease black and white thinking and foster tolerance is also discussed. [ABSTRACT FROM AUTHOR]

Abstract Glutamate, the main excitatory neurotransmitter in the vertebrate Central Nervous System, is involved in almost every aspect of brain physiology, and its signaling properties are severely affected in most neurodegenerative diseases. This neurotransmitter has to be efficiently removed from the synaptic cleft in order to prevent an over-stimulation of glutamate receptors that leads to neuronal death. Specific sodium-dependent membrane transporters, highly enriched in glial cells, elicit the clearance of glutamate. Once internalized, it is metabolized to glutamine by the glia-enriched enzyme Glutamine synthetase. Accumulated glutamine is released into the extracellular space for its uptake into pre-synaptic neurons and its conversion to glutamate that is packed into synaptic vesicles completing the glutamate/glutamine cycle. Diverse chemical compounds, like organophosphates, directly affect brain chemistry by altering levels of neurotransmitters in the synaptic cleft. Organophosphate compounds are widely used as pesticides, and all living organisms are continuously exposed to these substances, either in a direct or indirect manner. Its metabolites, like the diethyl dithiophosphate, are capable of causing brain damage through diverse mechanisms including perturbation of neuronal-glial cell interactions and have been associated with attention-deficit disorders and other mental illness. In order to characterize the neurotoxic mechanisms of diethyl dithiophosphate, we took advantage of the well characterized model of chick cerebellar Bergmann glia cultures. A significant impairment of [3H] d -Aspartate transport was found upon exposure to the metabolite. These results indicate that glia cells are targets of neurotoxic substances such as pesticides and that these cells might be critically involved in the associated neuronal death. Highlights • Glia cells are targets of neurotoxic substances, like DEDTP. • DEDTP reduces [3H]- d -Aspartate uptake. • DEDTP toxic effects are Ca2+-dependent. [ABSTRACT FROM AUTHOR]

Abstract: This paper is devoted to show and explain some applications of Lie Theory to solve some problems in Economics and Mathematical Finance. So we put forward and discuss mathematical aspects and approaches for several economic problems which have been previously considered in the literature. Besides we also show our advances on this topic, mentioning some open problems for future research. [Copyright &y& Elsevier]

Abstract: The relationships between genome wide association study-identified and replicated genetic variants associated with Alzheimer''s disease (AD) risk and disease progression or therapeutic responses in AD patients are almost unexplored. Seven hundred and one AD patients with at least 3 different cognitive evaluations and genotypic information for APOE and 6 genome wide association study-significant single-nucleotide polymorphisms were selected for this study. Mean differences in Global Deterioration Score and Mini Mental State Examination (MMSE) were evaluated using nonparametric tests, general linear model and mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor, memantine, or both. Relationships between therapeutic protocols, genetic markers, and progression were explored using stratified analysis looking for specific effects on progression in each therapeutic category separately. Neither calculation rendered a Bonferroni-corrected statistically significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared with GG carriers at the end of the follow-up (MMSE mean difference = −0.57; 95% confidence interval, −1.145 to 0.009; p = 0.047). This observation remained unaltered after covariate adjustments although it did not achieve predefined multiple testing significance threshold. The PICALM single-nucleotide polymorphism also displayed a significant effect protecting against rapid progression during pharmacogenetic assays although its observed effect displayed heterogeneity among AD therapeutic protocols (p = 0.039). None of the studied genetic markers were convincingly linked to AD progression or drug response. However, by using different statistical approaches, the PICALM rs3851179 marker displayed consistent but weak effects on disease progression phenotypes. [Copyright &y& Elsevier]

Summary: Background: Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. Methods: We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993–2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993–1998) and the period after the vaccine became available (1999–2003). Results: A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP–HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. Conclusions: In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen. [Copyright &y& Elsevier]

Parkinson''s disease (PD) is a common neurodegenerative disorder that produces progressive disability despite symptomatic treatment. Several strategies, including stereotaxic brain lesions, deep brain stimulation, transplants of dopamine cells and administration of neurotrophic factors, have been proposed to improve efficacy and to counteract the progression of the disease. We here report the effects of repetitive intracerebral infusion of basic fibroblast growth factor (bFGF) and glial-derived neurotrophic factor, up to 1 year, in Cynomolgus monkeys with long standing asymmetric parkinsonism produced by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The treatment with neurotrophic factors was initiated when the parkinsonian deficits were stable, 6 months after the administration of MPTP. The evaluation of the response to the neurotrophic factors was performed by blind observers using: clinical scales that measured global motor deficit, motor ability in both hands, apomorphine-induced rotation, determination of the levels of monoamine metabolites in cerebrospinal fluid, and 6-F18-fluoro-l-DOPA (F-DOPA) uptake in the striatum and histology. Both factors, but bFGF more so, improve motor behavior, dopamine metabolism, striatal F-DOPA uptake, and the number of dopamine neurons. The procedure is well tolerated and provides a strong background for efficacy and safety of this treatment in patients with PD. [Copyright &y& Elsevier]

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish ( n = 539) and German ( n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S ( p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17–14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology. [ABSTRACT FROM AUTHOR]

Objective The objective of this paper is to evaluate the security behavior of healthcare professionals in a real clinical setting. Method Standards, guidelines and recommendations on security and privacy best practices for staff personnel were identified using a systematic literature review. After a revision process, a questionnaire consisting of 27 questions was created and responded to by 180 health professionals from a public hospital. Results Weak passwords were reported by 62.2% of the respondents, 31.7% were unaware of the organization's procedures for discarding confidential information, and 19.4% did not carry out these procedures. Half of the respondents (51.7%) did not take measures to ensure that the personal health information on the computer monitor could not be seen by unauthorized individuals, and 57.8% were unaware of the procedure established to report a security violation. The correlation between the number of years in the position and good security practices was not significant (Pearson's r = 0.085, P = 0.254). Age was weakly correlated with good security practices (Pearson's r = −0.169, P = 0.028). A Mann–Whitney test showed no significant difference between the respondents’ security behavior as regards gender ( U = 2536, P = 0.792, n = 178). The results of the study suggest that more efforts are required to improve security education for health personnel. Conclusions It was found that both preventive and corrective actions are needed to prevent health staff from causing security incidents. Healthcare organizations should: identify the types of information that require protection, clearly communicate the penalties that will be imposed, promote security training courses, and define what the organization considers improper behavior to be and communicate this to all personnel. [ABSTRACT FROM AUTHOR]

Summary: Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 [95% CI 1·11–1·30]), rs9268856 (p=5·51 × 10−9; 0·809 [0·76–0·86]) and rs1980493 (p value=1·57 × 10−8, 0·775 [0·69–0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 [0·71–0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation: Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding: The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center. [Copyright &y& Elsevier]

Abstract: A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) gene has recently been described as a cause of familial and sporadic frontotemporal lobar degeneration. The aim of this study was to assess whether plasma progranulin (GRN) levels could be modulated by the presence of this repeat expansion. Sixty-five patients diagnosed with frontotemporal dementia and 10 family members with familial aggregation of disease were screened for the presence of the hexanucleotide repeat expansion in C9ORF72 gene, using a repeat-primed polymerase chain reaction method. Plasma GRN levels were measured in all subjects through enzyme-linked immunosorbent assay. Seven individuals with the repeat expansion were identified. No differences were found between C9ORF72 repeat expansion carriers and noncarriers (116.4 ± 21 ng/mL and 131.7 ± 36 ng/mL, respectively, p = 0.3). Analysis of family members did not disclose any difference in plasma GRN levels between carriers and noncarriers. In conclusion, plasma GRN levels are not influenced by the hexanucleotide repeat expansion in C9ORF72 gene, and therefore, cannot be used as a reliable biomarker to detect mutation carriers. [Copyright &y& Elsevier]

Abstract: Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer''s disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early-onset AD (mean age at onset of 52.9 years; range 31–64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d’Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new non-synonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations. [Copyright &y& Elsevier]

This work summarizes the results of a ten year surveillance programme on PCDD/F in ambient air carried out in Catalonia (Spain). The study has been conducted by the Dioxin Laboratory of Spanish Council for Scientific Research (CSIC) in collaboration with the Environment Department of the Catalonian Government. 175 samples have been collected throughout Catalonia from 1994 to 2004. Different sampling locations classified as industrial, traffic, urban, suburban and rural sites have been monitored in order to find the most contaminated zones as well as the ones with expected background concentrations. The highest concentrations found in this study were determined at the industrial locations. Concentrations ranging from 5 to 1196fg I-TEQ/m3, with a mean value of 140fg I-TEQ/m3 and from 10 to 357fg I-TEQ/m3, with a mean value of 72fg I-TEQ/m3 were determined in industrial and traffic sampling points, respectively. In contrast, the lowest concentrations were found in rural stations, ranging from 5 to 45fg I-TEQ/m3, with a mean value of 28fg I-TEQ/m3. The PCDD/F concentration trend in Catalonian ambient air shown a clear drop of the median values occurred during the study sampling period. A decline of about 70% was observed from 1997–1998 to 2003–2004. [Copyright &y& Elsevier]

Abstract: Abnormalities in the cerebral microvasculature are common in Alzheimer disease (AD). Expression levels of the water channels aquaporin 1 and aquaporin 4 (AQP1, AQP4) were examined in AD cases by gel electrophoresis and Western blotting, and densitometric values normalized with β-actin were compared with corresponding values in age-matched controls processed in parallel. In addition, samples of cases with Pick disease (PiD) were examined for comparative purposes. A significant increase in the expression levels of AQP1 was observed in AD stage II (following Braak and Braak classification). Individual variations were seen in advanced stages which resulted in non-significant differences between AD stages V–VI and age-matched controls. No differences in AQP1 levels were observed between familial AD cases (FAD, all of them at advanced stages) and corresponding age-matched controls. Immunohistochemistry showed increased AQP1 in astrocytes at early stages of AD. Double-labelling immunofluorescence and confocal microscopy disclosed AQP1 immunoreactivity at the cell surface of astrocytes which were recognized with anti-glial fibrillary acidic protein antibodies. No differences in the levels of AQP4 were observed in AD, FAD and PiD when compared with corresponding controls. These results indicate abnormal expression of AQP1 in astrocytes in AD, and they add support to the idea that abnormal regulation of mechanisms involved in the control of water fluxes occurs at early stages in AD. [Copyright &y& Elsevier]

Abstract: In this work, a comparison of TSP and PM10 samplers has been carried out with the purpose of evaluating the compatibility of the PCDD/Fs measurements between them and to comply with the current EC directive (Council directive 1999/30/EC) that regulates the particulate matter content, expressed as PM10 (particulate matter <10μm aerodynamic diameter) in ambient air due to their potential risk for human health. A total of 40 ambient air samples were collected for the analysis of PCDD/Fs from eight locations at different dates, using both TSP and PM10 samplers. Locations with diverse characteristic such as industrial, urban and traffic-affected zones were chosen. The results obtained in this work indicate that PCDD/F levels found using the TSP and PM10 sampling systems are comparable, or those from the latter are a bit lower, but these differences cannot be attributed to the sampling methodology. [Copyright &y& Elsevier]

The symposium Health and Medicines in Indigenous Populations of America was organized by the Council for International Organizations of Medical Sciences (CIOMS) Working Group on Clinical Research in Resource-Limited Settings (RLSs) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF). It was aimed to share and evaluate investigators' experiences on challenges and opportunities on clinical research and pharmacogenetics. A total of 33 members from 22 countries participated in 2 sessions: RIBEF studies on population pharmacogenetics about the relationship between ancestry with relevant drug-related genetic polymorphisms and the relationship between genotype and phenotype in Native Americans (session 1) and case examples of clinical studies in RLSs from Asia (cancer), America (diabetes and women health), and Africa (malaria) in which the participants were asked to answer in free text their experiences on challenges and opportunities to solve the problems (session 2). Later, a discourse analysis grouping common themes by affinity was conducted. The main result of session 1 was that the pharmacogenetics-related ancestry of the population should be considered when designing clinical studies in RLSs. In session 2, 21 challenges and 20 opportunities were identified. The social aspects represent the largest proportion of the challenges (43%) and opportunities (55%), and some of them seem to be common. The main discussion points were gathered in the Declaration of Mérida/T'Hó and announced on the Parliament of Extremadura during the CIOMS-RIBEF meeting in 4 of the major Latin American autochthonous languages (Náhualth, Mayan, Miskito, and Kichwa). The declaration highlighted the following: (1) the relevance of population pharmacogenetics, (2) the sociocultural contexts (interaction with traditional medicine), and (3) the education needs of research teams for clinical research in vulnerable and autochthonous populations. [ABSTRACT FROM AUTHOR]

• We determined the risk of exposure to Dirofilaria immitis in the stray dog population and people living in Puebla City, Mexico. • The prevalence of D. immitis in the canine stray population was 2.12%. Human seroprevalence was established at 5.11%. • Lack of environmental sanitation and the absence of control in the canine population may be risk factors of heartworm disease. The objective of this work was to determine the risk of exposure to Dirofilaria immitis in the stray dog population and people living in the metropolitan area of Puebla City, Mexico, using serologic methods. A total of 283 blood salmples were collected from dogs and 254 salmples from people. The canine samples were analyzed using a commercial kit to detect D. immitis antigens and the Knott test to detect microfilariae. Human samples were analyzed by ELISAs to detect antibodies against D. immitis and Wolbachia anti-WSP, as well as Western blot to identify specific bands of the parasite in the adult antigenic extract of D. immitis. Positive results were represented on a GIS map that included layers with geoenvironmental information relevant to parasite transmission in the study area. The prevalence of D. immitis in the canine stray population was 2.12 %, with positive cases found in individuals aged 1–10 years. Human seroprevalence was established at 5.11 %, with women and men similarly affected. By age, a significantly higher seroprevalence was observed in younger individuals (<18 years) than in the rest of the population. The geolocation of the results showed that positive cases were found in the environment (within 2 km) of potentially favorable areas for mosquito breeding. The importance of human influence in the creation and maintenance of favorable conditions for the transmission of canine and human dirofilariosis within an urban area is highlighted, both by the lack of environmental sanitation and by the absence of measures to limit or eliminate the canine reservoir population. [ABSTRACT FROM AUTHOR]

The County of Baix Llobregat (Barcelona, Catalonia, Spain) presents a high prevalence of familial frontotemporal dementia (FTD) in the presence of P301L mutation in the MAPT gene. To evaluate a possible unique founder effect of P301L, and its age, the analysis of 20 single-nucleotide polymorphisms covering 50 kb and 12 single-nucleotide polymorphisms located along 30 Mb around the mutation was performed by developing 2 multiplex single-base extension reactions. In addition, families with affected and healthy individuals from France and Italy were analyzed. The FTD-affected individuals from Barcelona carried the same 50-kb haplotype linked to P301L mutation, suggesting a unique common ancestor, as opposed to French patients. Italian patients are also probably descendants of a unique ancestor, which would be different from that of Barcelona. Diversity of 30-Mb haplotypes found in Barcelona and the inference of the mutation age in these populations, among other reasons, suggest that prevalence of FTD linked to P301L MAPT mutation is the result of a locally originated mutation. • Two SBE reactions to analyze 50 kb and 30 Mb around P301L mutation were developed. • P301L mutation in MAPT in Barcelona is due to a unique mutational event. • This Barcelonan mutational event could be the result of a local mutation. • Haplogroup linked to P301L of Barcelona is also present in France. • Italy, likewise Barcelona, could have suffered another unique founder effect of P301L. [ABSTRACT FROM AUTHOR]

The tubulin alpha 4a ( TUBA4A ) gene has been recently associated with amyotrophic lateral sclerosis. Interestingly, some of the mutation carriers were also diagnosed with frontotemporal degeneration (FTD) or mild cognitive impairment. With the aim to investigate the role of TUBA4A in FTD, we screened TUBA4A in a series of 814 FTD patients from Spain. Our data did not disclose any nonsense or missense variant in the cohort, thus suggesting that TUBA4A mutations are not associated with FTD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels.Design: Prospective case-control study.Setting: University hospital.Patient(s): A total of 53 preeclamptic and 72 normal pregnant women.Intervention(s): Maternal and cord blood samples and placental tissue samples were obtained.Main Outcome Measure(s): Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured.Result(s): The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo.Conclusion(s): Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women. [ABSTRACT FROM AUTHOR]

Abstract: A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR] = 4.12, 95% confidence interval [CI] = 1.21–14.00, p = 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR = 4.11, 95% CI = 2.99–5.68, p = 5.27×10−18). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD. [Copyright &y& Elsevier]

Abstract: The present research is aimed at assessing the role of 3 estrogen receptor alpha (ESR1) gene variants in late onset Alzheimer''s disease (AD) susceptibility. One thousand one hundred thirteen unrelated late onset sporadic AD patients, 1109 healthy controls and 121 neurologically healthy elderly controls were used to carry out case-control genetic association studies with ESR1 rs3844508, rs2234693, and ESR1 noncoding deletion 1 (ESR1-NCD1) polymorphisms. Thirty-five healthy male samples were used for molecular analyses. The rs2234693 polymorphism is associated with AD in our population (odds ratio [OR], 1.29; p = 0.008). The rs3844508 marker confers protection against AD in males (OR, 0.57; p = 0.001) and the deletion ESR1-NCD1 is a risk factor for AD in women (OR, 1.67; p < 0.001). Molecular analyses on ESR1-NCD1 indicate that this deletion confers a higher response to estradiol activity on ESR1 receptor and it is also associated with differential expression of ESR1 isoforms. Our results support the involvement of ESR1 gene in AD and point to the existence of sexual dimorphism for ESR1 markers. In addition, carriers of ESR1-NCD1 deletion could overrespond to estradiol action. [Copyright &y& Elsevier]