Diet patterns associated with cognitive decline: methods to harmonize data from European and US cohort studies.

The impact of dietary intake on cognitive outcomes and dementia prevention is a topic of increasing interest. Meta-analyses of observational studies, mostly conducted within US and European populations, have reported benefits of healthy diet patterns on cognitive performance, but results from individual studies have been inconsistent. These inconsistencies are likely due to the diverse methodology used in studies, including different diet and cognitive function assessment instruments, follow-up periods, and analytical methods, which make drawing conclusions relevant to dietary guidance challenging. The objective of this project is to describe a protocol to conduct a retrospective harmonization study on dietary intake and cognitive health using data from European and US studies. The recommendations resulting from the project can be used to support evidence-based synthesis for future iterations of the Dietary Guidelines for Americans or other population-based dietary guidance. Additionally, this study will serve as a harmonization guide for future research on the relationship between diet patterns and cognition. The approach outlined ultimately aims to optimize resources and expedite research efforts for dementia prevention.

PRODISCAT Pediàtric: un qüestionari útil per detectar la dislèxia en pediatria / Prodiscat Pediàtric: un cuestionario útil para la detección dela dislexia en pediatría / Pediatric PRODISCAT: A useful questionnaire for the detection of dyslexia in children

Fonament. La dislèxia és el trastorn del neurodesenvolupament més prevalent entre els escolars. Es caracteritza perdificultats en la precisió i/o la fluïdesa lectores, en el reconeixement de paraules i en les capacitats de lletrejar i descodificar. Aquestes dificultats comporten problemes en lacomprensió lectora i en l’adquisició de vocabulari i coneixements, de manera que la competència finalment adquiridaés inferior a l’esperada per l’edat, les capacitats intel·lectuals, la motivació o el mètode educatiu rebut durant l’escolarització. El dèficit persisteix en l’edat adulta i provocaproblemes acadèmics, emocionals, socials i econòmics. Hiha tractaments efectius per pal·liar-ne els efectes.Objectiu. L’objectiu d’aquest estudi és determinar si elqüestionari PRODISCAT Pediàtric és una eina útil de cribratge per detectar dislèxia.Mètode. El qüestionari s’ha administrat a escolars d’entre 4i 11 anys amb diagnòstic de dislèxia, així com a infantssense el trastorn (grup control), en una mostra de 236 escolars als quals també s’ha fet una valoració neuropsicològica exhaustiva. S’ha calculat la sensibilitat i l’especificitatdel qüestionari com a eina de cribratge de dislèxia.Resultats. Les anàlisis mostren alts nivells de sensibilitat(94,2% en els infants de 4-7 anys i 96% en els de 8-11anys) i d’especificitat (77,8% en els infants de 4-7 anys i73,8% en els de 8-11 anys). (AU)

Fundamento. La dislexia es el trastorno del neurodesarrollo másprevalente entre los escolares. Se caracteriza por dificultades en laprecisión y/o la fluidez lectora, en el reconocimiento de palabras yen las capacidades de deletreo y descodificación. Estas dificultades comportan problemas en la comprensión lectora y en la sición de vocabulario y de conocimientos, siendo la competenciafinalmente adquirida inferior a la esperada por edad, capacidadesintelectuales, motivación o método educativo recibido durante laescolarización. El déficit persiste en la edad adulta y provoca problemas académicos, emocionales, sociales y económicos. Existentratamientos efectivos para paliar sus efectos.Objetivo. El objetivo del presente estudio es determinar si el cuestionario PRODISCAT Pediàtric es una herramienta útil de cribadode dislexia.Método. El cuestionario se ha administrado a escolares de entre 4y 11 años con diagnóstico de dislexia, así como a niños y niñas sinel trastorno (grupo control) en una muestra total de 236 escolaresa los que se les ha realizado también una valoración neuropsicológica exhaustiva. Se ha calculado la sensibilidad y especificidad delcuestionario como herramienta de cribado de dislexia.Resultados. Los análisis muestran altos niveles de sensibilidad(94,2% en los niños y niñas de 4-7 años y 96% los de 8-11 años)y de especificidad (77,8% en los niños y niñas de 4-7 años y73,8% en los de 8-11 años).Conclusiones. Los resultados indican que el PRODISCAT Pediàtricpuede ser una herramienta útil de cribado para detectar dislexiaen esta franja de edad. (AU)

Background. Dyslexia is the most frequent neurodevelopmental disorder among school-aged children. It is characterized by difficulties in reading accuracy, fluency, word recognition, spelling, anddecoding skills. These difficulties cause problems in reading comprehension and in the acquisition of vocabulary and knowledge.The competence finally acquired by dyslexics is lower than expected for their age, intellectual capacity, motivation, or the quality ofthe education received. This deficit persists into adulthood, and itcauses academic, emotional, social, and economic problems.There are effective treatments to palliate the effects of dyslexia.Objective. The aim of this study is to determine the usefulness of thescreening questionnaire PRODISCAT Pediàtric to detect dyslexia.Method. We administered the questionnaire to dyslexic school children between 4 and 11 years of age and to a control group in a sample of 236 children. Both groups had received neuropsychological assessments. Sensitivity and specificity of the questionnairewas calculated with the aim of validating the questionnaire as ascreening tool.Results. The analysis shows high levels of sensitivity (94.2% in4- to 7-year-old children and 96% in 8- to 11-year-old children)and of specificity (77.8% in 4- to 7-year-old children and 73.8%in 8- to 11-year-old children).Conclusions. The results indicate that the screening questionnairePRODISCAT Pediàtric can be a useful tool to detect dyslexia. (AU)

A molecular study of tick-borne haemoprotozoan parasites (Theileria and Babesia) in small ruminants in Northern Tunisia.

In this study, the frequency of Theileria and Babesia species in sheep and goats was assessed via reverse line blotting (RLB). A total of 263 apparently healthy sheep and goats, from 16 randomly selected flocks located in 9 localities situated in 3 bioclimatic zones in Tunisia, were investigated for the blood protozoans. RLB hybridization with polymerase chain reaction detected only Theileria ovis in sheep and goats, accounting for 22.4% (95% confidence interval [CI]: 17.6-27.1%) positive samples. The infection rate in sheep (28.1%; 95% CI: 23.8-32.3%) was higher than in goats (4.7%; 95% CI: -10.9 to 20.4%). Neither Babesia nor mixed infections were detected. Only two Ixodid tick species (Rhipicephalus turanicus and Rhipicephalus bursa) were collected from the examined sheep and goats in 5 localities. R. turanicus was the dominant species (95.5%) collected mainly in the humid zone, while apparently rare in the sub-humid zone. R. bursa was the only species collected in the semi-arid area. RLB analysis identified six different piroplasms in ticks, with an overall prevalence of 31.5% (95% CI: 28.1-34.9%). Twenty percent (95% CI: 14.4-25.5%) of the collected ticks tested positive for Theileria spp., 3% (95% CI: -5.6 to 11.6%) for Babesia spp. and 0.9% (95% CI: -8.1 to 9.9%) of the ticks harbored both genera; several of these species are not known to occur in small ruminants. This is the first report on the detection of Theileria and Babesia species DNA in small ruminants and ticks in Tunisia.

Prevalence and genetic diversity of piroplasm species in horses and ticks from Tunisia.

The genetic diversity and prevalence of Babesia and Theileria species in the equine population of Tunisia were studied using reverse line blot (RLB) hybridization on blood samples and unfed adult ticks collected from apparently healthy horses from three bioclimatic zones in Tunisia. Piroplasms were identified in 13 of 104 of the horse blood samples analyzed (12.5%) and five genotype groups were identified: Theileria equi group A (nine animals, 8.7%), group C (one animal, 1.0%) and group D (three animals, 2.9%), and Babesia caballi groups A and B (one animal each). All horses from the semi-arid zone were negative and prevalence in the humid and sub-humid zones were 12.9% and 20.0%, respectively. Three Ixodid tick species (Hyalomma marginatum, Hyalomma excavatum and Rhipicephalus bursa) were collected from examined horses and equine piroplasms were detected in 10.8% of them. T. equi groups A and D (9.2%), and B. caballi group B (1.6%) were identified in ticks. This work represents the first epidemiological report of equine piroplasmosis in Tunisia. Results showed a high level of diversity within the 18S rRNA gene of equine piroplasm species, and confirmed the presence in Tunisia of two T. equi genetic groups, C and D, only reported before in South Africa and Sudan.

Assessment of exposure to piroplasms in sheep grazing in communal mountain pastures by using a multiplex DNA bead-based suspension array.

BACKGROUND: Piroplasms are tick-borne hemoprotozoans with a major impact on extensive management systems. Detection of sub-clinical low-level carriers, which can act as source of infection for vector ticks, is key to protect livestock trade and facilitate preventive control programs. The purpose of this study was to develop a method for the detection of ovine piroplasms and to use it in a field study aimed at investigating piroplasms infection in semi-extensive production systems in the Basque Country (northern Spain). METHODS: A DNA bead-based suspension array using the Luminex xMAP technology that included a generic Theileria-Babesia control probe, 6 species-specific probes, and an internal control probe was developed to detect and identify piroplasms that infect sheep. To monitor piroplasm infection in clinically healthy sheep from 4 flocks that share communal mountain pastures, blood samples were collected during 2 grazing seasons. RESULTS: Piroplasms were detected in 48% (214/446) of blood samples, nearly half of them (49.1%, 105/214) as mixed infections. Five different piroplasms were identified: Theileria sp. OT3 in 34.8% of the samples, Theileria ovis in 20.9%, and at lower prevalences Babesia motasi (12.3%), Theileria luwenshuni/OT1 (10.5%) and Babesia ovis (6.3%). Despite differences among flocks associated to differences in management, an increasing trend in the incidence of piroplasm infection with increasing age of animals after increased tick exposure was observed. This increment could be attributed to continued re-infection associated with re-exposure to ticks at grazing. Ticks were collected from animals (4 species) and vegetation (8 species), and associations between tick abundance seasonality and risk of infection with the different piroplasms were established. CONCLUSION: The multiplex Luminex xMAP procedure is a rapid and high throughput technique that provided highly specific and sensitive identification of single and mixed piroplasm infections in blood of sheep carriers. This study confirmed a situation of endemic stability for piroplasm infection in the region, where infection is present in the absence of clinical signs, and mountain grazing allows for sufficient inoculation rates to maintain such situation.

Development and evaluation of a real-time PCR assay for the quantitative detection of Theileria annulata in cattle.

BACKGROUND: The tick-borne apicomplexan bovine parasite Theileria annulata is endemic in many tropical and temperate areas, including Minorca (Balearic Islands, Spain). Real-time PCR is widely used for the detection of piroplasms but quantification is not commonly considered. RESULTS: We developed a real-time quantitative PCR (qPCR) assay for the detection and quantification of T. annulata that included an internal amplification control (IAC) to monitor for the presence of potential inhibitors. Specificity, sensitivity, precision, linear range and PCR efficiency were calculated and different methods for transformation of quantification cycle (Cq) values into quantities (Q) were evaluated. The assay was able to detect (100% probability) and quantify (linear response) 100 gene copies, and clinical sensitivity was set at 10 T. annulata per µl of blood. The assay was then validated on 141 bovine blood samples analyzed in parallel by a Luminex® suspension array, showing the utility of the qPCR assay developed here for the detection and quantification of the parasite in field conditions. Once validated it was used to monitor T. annulata parasitaemia throughout a year in 8 carrier animals from a farm in Minorca. CONCLUSIONS: The developed qPCR assay offers a reliable and simple way to quantify T. annulata infection loads, which could prove crucial in studying the role of carrier animals as a source of the infection, or assessing the efficacy of treatment and control measures.

A highly sensitive DNA bead-based suspension array for the detection and species identification of bovine piroplasms.

Piroplasms are among the most harmful tick-borne pathogens for livestock and sensitive and specific diagnostic methods for rapid detection and identification of the different species are needed for effective control. Reverse Line Blot has been the molecular technique of choice but it is laborious, time-consuming and highly susceptible to subjective variation in the interpretation of the hybridisation signal. Here, an oligonucleotide multiplex suspension microarray (Luminex® microsphere system) was developed for bovine piroplasms. Probes previously used in Reverse Line Blot for Babesia divergens, Babesia bovis, Babesia occultans, Babesia bigemina and Theileria buffeli, and a catch-all Theileria and Babesia control probe, were included in the Luminex assay together with newly designed probes for Theileria annulata and Babesia major. An internal amplification control that was detected with a Luminex probe was included to monitor for inhibition. Serially diluted linearised recombinant plasmids of the different species were used to assess the analytical sensitivity and specificity, and the detection limit of the Luminex assay was determined using serial dilutions of infected blood from an animal with a known level of T. annulata parasitaemia. The assay was then validated on 214 bovine blood samples analysed in parallel by Reverse Line Blot and Luminex. The Luminex assay proved to be highly specific and more sensitive than Reverse Line Blot, detecting 0.05 parasites/µl of blood. Technically, the Luminex procedure was rapid, provided high throughput screening, transformed the subjective interpretation of Reverse Line Blot results into numerical objective values, and allowed more flexibility in array preparation than Reverse Line Blot. The method described herein can substantially improve the detection of piroplasm carriers and thus better protect livestock trade and facilitate preventive control programs.

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells.

Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.