Observation of Masturbation After Visual Sexual Stimuli From Conspecifics in a Captive Male Bearded Capuchin (Sapajus libidinosus).

Masturbation is part of the natural behavioral repertoire of primates, with visual sexual stimuli known to trigger this behavior. Here, we report masturbation events triggered by visual sexual stimulus (VSS) in the South American primate Sapajus libidinosus. We observed a multi-male multi-female captive colony of 17 bearded capuchins between January and October 2014. Over this period, we registered 11 copulation events, 68 attempt copulations, and five masturbation events. The same low-ranking male (named Fu) performed all masturbation events. Fu directly looked at other individuals engaged in sexual displays while he masturbated in three events. The masturbation events associated with VSS lasted up to 2 min and 40 s. Our observations show that VSS can trigger masturbation in capuchin monkeys. The low hierarchy rank of the male, and the consequent lack of mating opportunities in the multi-male multi-female recently formed group in captivity, may have prompted the masturbation events.

Chemical composition, antioxidant, and antimicrobial activities of six commercial essential oils.

Essential oils (EOs) and their components extracted from medicinal and aromatic plants are used in several areas, such as perfumery and chemical, cosmetic, food, and pharmaceutical industries. Considering the different applications of EOs, this work aimed to screen the composition and the bioactivities properties of the EOs of Foeniculum vulgare, Helichrysum stoechas, Mentha pulegium, Pinus pinaster, Ruta graveolens, and Thymus mastichina. Gas chromatography-mass spectrometry revealed the presence of different compounds in EOs F. vulgare (12), H. stoechas (27), M. pulegium (8), P. pinaster (24), R. graveolens (8), and T. mastichina (16). All the EOs showed antioxidant activity acting through inhibition of lipid peroxidation, while only two EOs (H. stoechas and M. pulegium) scavenged the free radicals of DPPH. Mentha pulegium and T. mastichina EOs showed the strongest antimicrobial activity. Also, the effect on the fibroblast's viability was directly proportional to the EOs concentration, and the highest cytotoxic effect was registered with R. graveolens EO. The present study revealed significant bioactive properties of different EOs, highlighting M. pulegium and T. mastichina EOs to be considered in further studies for potential use in the food and pharmaceutical industries, due to their antioxidant and antimicrobial properties.

Chemical Composition of Macroalgae Polysaccharides from Galician and Portugal Coasts: Seasonal Variations and Biological Properties.

Crude polysaccharides extracted from the Codium sp. and Osmundea sp. macroalgae collected in different seasons (winter, spring and summer) from the Galician and North Portugal coasts were characterised, aiming to support their biomedical application to wound healing. An increase in polysaccharides' sulphate content was registered from winter to summer, and higher values were obtained for Osmundea sp. In turn, the monosaccharide composition constantly changed with a decrease in glucose in Osmundea sp. from spring to winter. For Codium sp., a higher increase was noticed regarding glucose content in the Galician and Portugal coasts. Galactose was the major monosaccharide in all the samples, remaining stable in all seasons and collection sites. These results corroborate the sulphate content and antioxidant activity, since the Osmundea sp.-derived polysaccharides collected in summer exhibited higher scavenging radical ability. The biocompatibility and wound scratch assays revealed that the Osmundea sp. polysaccharide extracted from the Portugal coast in summer possessed more potential for promoting fibroblast migration. This study on seasonal variations of polysaccharides, sulphate content, monosaccharide composition and, consequently, biological properties provides practical guidance for determining the optimal season for algae harvest to standardise preparations of polysaccharides for the biomedical field.

Zimbro (Juniperus communis L.) as a Promising Source of Bioactive Compounds and Biomedical Activities: A Review on Recent Trends.

Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases.

Single-implant mandibular overdentures: Clinical, radiographic, and patient-reported outcomes after a 5-year follow-up.

STATEMENT OF PROBLEM: Previous studies on single-implant mandibular overdentures have reported favorable results for clinical and patient-reported outcomes. However, information from longer term clinical studies is lacking. PURPOSE: The purpose of this clinical study was to assess clinical, radiographic, and patient-reported outcomes of edentulous individuals rehabilitated with single-implant mandibular overdentures after a 5-year follow-up. MATERIAL AND METHODS: A prospective clinical study was performed including completely edentulous individuals who received new conventional complete dentures and then an external hexagon implant in the mandibular midline region, followed by the incorporation of a retention system (O-ring/ball attachment; Neodent). Data collection occurred at baseline and 3, 6, 12, 24, and 60 months after implant loading. Assessed outcomes included implant stability, peri-implant soft tissue condition, peri-implant marginal bone level, satisfaction with the prostheses, and oral health-related quality of life (OHRQoL). Clinical maintenance events were also recorded. Descriptive statistics, incidence rates, Wilcoxon Signed Ranks test, and Generalized Estimating Equation regression were used for data analysis (α=.05). RESULTS: Thirty of 34 eligible participants attended the 5-year follow-up visit, mean ±standard deviation age was 68.1 ±7.8 years, and 70% were women. The overall implant survival rate was 88.9%. After 5 years, the OHRQoL showed statistically significant improvement for all evaluation periods compared with baseline (P<.001). Regarding satisfaction with the mandibular denture, a significant increase was found between all evaluation periods compared with baseline in terms of comfort, stability, and ability to masticate (P<.001). Implant stability significantly increased (P=.003), and a mean bone loss of 1.46 mm was observed compared with baseline measures. The most frequent maintenance event was replacement of the O-ring matrix (n=80). Twenty-one midline fractures of the overdenture occurred in 14 study participants. No significant changes in peri-implant soft tissue conditions were observed. CONCLUSIONS: A single-implant mandibular overdenture effectively maintained the positive effect of the intervention on oral health-related quality of life and patient satisfaction, stable peri-implant condition, and acceptable rates of prosthetic events.

A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia.

Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis. We used genome-wide linkage analysis, NGS, and repeat analysis to identify an (ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region 1p32.2 as the cause of autosomal-dominant SCA; this region has been previously linked to SCA37. The non-pathogenic and pathogenic alleles have the configurations [(ATTTT)7-400] and [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90], respectively. (ATTTC)n insertions are present on a distinct haplotype and show an inverse correlation between size and age of onset. In the DAB1-oriented strand, (ATTTC)n is located in 5' UTR introns of cerebellar-specific transcripts arising mostly during human fetal brain development from the usage of alternative promoters, but it is maintained in the adult cerebellum. Overexpression of the transfected (ATTTC)58 insertion, but not (ATTTT)n, leads to abnormal nuclear RNA accumulation. Zebrafish embryos injected with RNA of the (AUUUC)58 insertion, but not (AUUUU)n, showed lethal developmental malformations. Together, these results establish an unstable repeat insertion in DAB1 as a cause of cerebellar degeneration; on the basis of the genetic and phenotypic evidence, we propose this mutation as the molecular basis for SCA37.

Mutational mechanism for DAB1 (ATTTC)n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution.

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.

Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4.

Hereditary autosomal-recessive cerebellar ataxias are a genetically and clinically heterogeneous group of disorders. We used homozygosity mapping and exome sequencing to study a cohort of nine Portuguese families who were identified during a nationwide, population-based, systematic survey as displaying a consistent phenotype of recessive ataxia with oculomotor apraxia (AOA). The integration of data from these analyses led to the identification of the same homozygous PNKP (polynucleotide kinase 3'-phosphatase) mutation, c.1123G>T (p.Gly375Trp), in three of the studied families. When analyzing this particular gene in the exome sequencing data from the remaining cohort, we identified homozygous or compound-heterozygous mutations in five other families. PNKP is a dual-function enzyme with a key role in different pathways of DNA-damage repair. Mutations in this gene have previously been associated with an autosomal-recessive syndrome characterized by microcephaly; early-onset, intractable seizures; and developmental delay (MCSZ). The finding of PNKP mutations associated with recessive AOA extends the phenotype associated with this gene and identifies a fourth locus that causes AOA. These data confirm that MCSZ and some forms of ataxia share etiological features, most likely reflecting the role of PNKP in DNA-repair mechanisms.

Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurological conditions. Their main pathogenic mechanisms are thought to involve alterations in endomembrane trafficking, mitochondrial function, and lipid metabolism. With a combination of whole-genome mapping and exome sequencing, we identified three mutations in REEP2 in two families with HSP: a missense variant (c.107T>A [p.Val36Glu]) that segregated in the heterozygous state in a family with autosomal-dominant inheritance and a missense change (c.215T>A [p.Phe72Tyr]) that segregated in trans with a splice site mutation (c.105+3G>T) in a family with autosomal-recessive transmission. REEP2 belongs to a family of proteins that shape the endoplasmic reticulum, an organelle that was altered in fibroblasts from an affected subject. In vitro, the p.Val36Glu variant in the autosomal-dominant family had a dominant-negative effect; it inhibited the normal binding of wild-type REEP2 to membranes. The missense substitution p.Phe72Tyr, in the recessive family, decreased the affinity of the mutant protein for membranes that, together with the splice site mutation, is expected to cause complete loss of REEP2 function. Our findings illustrate how dominant and recessive inheritance can be explained by the effects and nature of mutations in the same gene. They have also important implications for genetic diagnosis and counseling in clinical practice because of the association of various modes of inheritance to this new clinico-genetic entity.

Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex.

Tissue-specific transcriptional activators initiate differentiation towards specialized cell types by inducing chromatin modifications permissive for transcription at target loci, through the recruitment of SWItch/Sucrose NonFermentable (SWI/SNF) chromatin-remodelling complex. However, the molecular mechanism that regulates SWI/SNF nuclear distribution in response to differentiation signals is unknown. We show that the muscle determination factor MyoD and the SWI/SNF subunit BAF60c interact on the regulatory elements of MyoD-target genes in myoblasts, prior to activation of transcription. BAF60c facilitates MyoD binding to target genes and marks the chromatin for signal-dependent recruitment of the SWI/SNF core to muscle genes. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38α kinase is the signal that promotes incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model by which pre-assembled BAF60c-MyoD complex directs recruitment of SWI/SNF to muscle loci in response to differentiation cues.

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes ß-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.

Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia.

Hereditary spastic paraplegias are heterogeneous neurological disorders characterized by a pyramidal syndrome with symptoms predominantly affecting the lower limbs. Some limited pyramidal involvement also occurs in patients with an autosomal recessive neurocutaneous syndrome due to ALDH18A1 mutations. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), an enzyme that catalyses the first and common step of proline and ornithine biosynthesis from glutamate. Through exome sequencing and candidate gene screening, we report two families with autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment, without any cutaneous abnormality. More interestingly, we also identified monoallelic ALDH18A1 mutations segregating in three independent families with autosomal dominant pure or complex hereditary spastic paraplegia, as well as in two sporadic patients. Low levels of plasma ornithine, citrulline, arginine and proline in four individuals from two families suggested P5CS deficiency. Glutamine loading tests in two fibroblast cultures from two related affected subjects confirmed a metabolic block at the level of P5CS in vivo. Besides expanding the clinical spectrum of ALDH18A1-related pathology, we describe mutations segregating in an autosomal dominant pattern. The latter are associated with a potential trait biomarker; we therefore suggest including amino acid chromatography in the clinico-genetic work-up of hereditary spastic paraplegia, particularly in dominant cases, as the associated phenotype is not distinct from other causative genes.

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP.

Modifiers of (CAG)(n) instability in Machado-Joseph disease (MJD/SCA3) transmissions: an association study with DNA replication, repair and recombination genes.

Twelve neurological disorders are caused by gene-specific CAG/CTG repeat expansions that are highly unstable upon transmission to offspring. This intergenerational repeat instability is clinically relevant since disease onset, progression and severity are associated with repeat size. Studies of model organisms revealed the involvement of some DNA replication and repair genes in the process of repeat instability, however, little is known about their role in patients. Here, we used an association study to search for genetic modifiers of (CAG)n instability in 137 parent-child transmissions in Machado-Joseph disease (MJD/SCA3). With the hypothesis that variants in genes involved in DNA replication, repair or recombination might alter the MJD CAG instability patterns, we screened 768 SNPs from 93 of these genes. We found a variant in ERCC6 (rs2228528) associated with an expansion bias of MJD alleles. When using a gene-gene interaction model, the allele combination G-A (rs4140804-rs2972388) of RPA3-CDK7 is also associated with MJD instability in a direction-dependent manner. Interestingly, the transcription-coupled repair factor ERCC6 (aka CSB), the single-strand binding protein RPA, and the CDK7 kinase part of the TFIIH transcription repair complex, have all been linked to transcription-coupled repair. This is the first study performed in patient samples to implicate specific modifiers of CAG instability in humans. In summary, we found variants in three transcription-coupled repair genes associated with the MJD mutation that points to distinct mechanisms of (CAG)n instability.

The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies.

BACKGROUND: Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology. SUMMARY: Our objective was to assess the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies. The MEDLINE, ISI Web of Science and Scopus databases were searched (1983-2013) for studies performed in well-defined populations and geographical regions. Two independent reviewers assessed the studies and extracted data and predefined methodological parameters. Overall, 22 studies were included, reporting on 14,539 patients from 16 countries. Multisource population-based studies yielded higher prevalence values than studies based primarily on hospitals or genetic centres. The prevalence range of dominant HCA was 0.0-5.6/10(5), with an average of 2.7/10(5) (1.5-4.0/10(5)). Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease was the most common dominant ataxia, followed by SCA2 and SCA6. The autosomal recessive (AR) HCA (AR-HCA) prevalence range was 0.0-7.2/10(5), the average being 3.3/10(5) (1.8-4.9/10(5)). Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. The prevalence of autosomal dominant (AD) HSP (AD-HSP) ranged from 0.5 to 5.5/10(5) and that of AR-HSP from 0.0 to 5.3/10(5), with pooled averages of 1.8/10(5) (95% CI: 1.0-2.7/10(5)) and 1.8/10(5) (95% CI: 1.0-2.6/10(5)), respectively. The most common AD-HSP form in every population was spastic paraplegia, autosomal dominant, type 4 (SPG4), followed by SPG3A, while SPG11 was the most frequent AR-HSP, followed by SPG15. In population-based studies, the number of families without genetic diagnosis after systematic testing ranged from 33 to 92% in the AD-HCA group, and was 40-46% in the AR-HCA, 45-67% in the AD-HSP and 71-82% in the AR-HSP groups. KEY MESSAGES: Highly variable prevalence values for HCA and HSP are reported across the world. This variation reflects the different genetic make-up of the populations, but also methodological heterogeneity. Large areas of the world remain without prevalence studies. From the available data, we estimated that around 1:10,000 people are affected by HCA or HSP. In spite of advances in genetic research, most families in population-based series remain without identified genetic mutation after extensive testing. © 2014 S. Karger AG, Basel.

Optimization of liquid overlay technique to formulate heterogenic 3D co-cultures models.

Three-dimensional (3D) cell culture models of solid tumors are currently having a tremendous impact in the in vitro screening of candidate anti-tumoral therapies. These 3D models provide more reliable results than those provided by standard 2D in vitro cell cultures. However, 3D manufacturing techniques need to be further optimized in order to increase the robustness of these models and provide data that can be properly correlated with the in vivo situation. Therefore, in the present study the parameters used for producing multicellular tumor spheroids (MCTS) by liquid overlay technique (LOT) were optimized in order to produce heterogeneous cellular agglomerates comprised of cancer cells and stromal cells, during long periods. Spheroids were produced under highly controlled conditions, namely: (i) agarose coatings; (ii) horizontal stirring, and (iii) a known initial cell number. The simultaneous optimization of these parameters promoted the assembly of 3D characteristic cellular organization similar to that found in the in vivo solid tumors. Such improvements in the LOT technique promoted the assembly of highly reproducible, individual 3D spheroids, with a low cost of production and that can be used for future in vitro drug screening assays.

Familial hemiplegic migraine due to L263V SCN1A mutation: discordance for epilepsy between two kindreds from Douro Valley.

BACKGROUND: SCN1A is the most relevant gene in epilepsy. Only seven SCN1A mutations have been identified in 10 familial hemiplegic migraine (FHM) kindreds worldwide. CASES AND KINDREDS: In 2009, we presented a kindred with FHM due to the L263V SCN1A mutation. In the current study, we report a novel FHM3 kindred from the same village. The first family exhibited the co-occurrence of FHM and epilepsy. No case of epilepsy was observed in the new kindred. An L263V mutation was found in all patients, and the haplotype analysis supports a unique mutational event. COMMENTS: Despite its bioelectric activity, the SCN1A L263V mutation most likely requires a combination of several endogenous or environmental induction stimuli to attain an epileptogenic threshold.

Nystagmus as an early ocular alteration in Machado-Joseph disease (MJD/SCA3).

BACKGROUND: Machado-Joseph disease (MJD), also named spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. Although nystagmus is one of the most frequently reported ocular alterations in MJD patients its behaviour during the course of the disease, namely in its early stages, has only recently started to be investigated. The main goal of this work was to characterize the frequency of nystagmus in symptomatic and presymptomatic carriers of the MJD mutation, and investigate its usefulness as an early indicator of the disease. METHODS: We conducted an observational study of Azorean MJD family members, comprising a total of 158 subjects which underwent neurological evaluation. Sixty eight were clinically and molecularly diagnosed with MJD, 48 were confirmed asymptomatic carriers and 42 were confirmed non-carriers of the MJD mutation. The frequency of nystagmus was calculated for the 3 groups. RESULTS: Nystagmus was present in 88% of the MJD patients. Seventeen percent of the at-risk subjects with a carrier result in the molecular test and none of the 42 individuals who received a non-carrier test result displayed nystagmus (p < 0.006). Although not reaching statistical significance, symptomatic subjects showing nystagmus had a tendency for a higher length of the CAG tract in the expanded allele, when compared to individuals who did not have nystagmus. CONCLUSIONS: The frequency of nystagmus in asymptomatic carriers and its absence in non-carriers of the mutation, suggests that nystagmus may appear before gait disturbance and can thus be considered an early sign of MJD.

The prevalence of familial hemiplegic migraine with cerebellar ataxia and spinocerebellar ataxia type 6 in Portugal.

BACKGROUND: CACNA1A gene disorders present a variable familial phenotype of ataxia, migraine with aura, and/or hemiplegic migraine. Prevalence data for these conditions are scarce. OBJECTIVE: The aim of this study is to report a minimal prevalence estimate for familial hemiplegic migraine with cerebellar ataxia and spinocerebellar ataxia type 6 in Portugal. METHODS: This is a multisource population-based prevalence study. Patients and families with spinocerebellar ataxia type 6 and familial hemiplegic migraine and cerebellar ataxia identified through the Portuguese survey of hereditary ataxias and spastic paraplegias were re-evaluated. Prevalent patients were confirmed to be alive and affected at the 1st of January 2013. RESULTS: One family with spinocerebellar ataxia type 6 and 2 families with other CACNA1A gene mutations were identified. From these families, 23 patients were alive and living in Portugal in the prevalence day, for an estimated national prevalence per 100,000 inhabitants of 0.21 for familial hemiplegic migraine with cerebellar ataxia and of 0.01 for spinocerebellar ataxia type 6. CONCLUSION: The prevalence of familial hemiplegic migraine with cerebellar ataxia and spinocerebellar ataxia type 6 are both probably low in Portugal.

Web-based cognitive training: patient adherence and intensity of treatment in an outpatient memory clinic.

BACKGROUND: Cognitive training has been playing an increasing role in the treatment of patients with cognitive deficits. This type of intervention, namely its intensity, can be optimized by incorporating information technology-based systems. OBJECTIVE: The intent of the study was to determine the treatment intensity and patient adherence to home-based cognitive training strategies (Web-based cognitive training). METHODS: A cohort of 45 patients with neurologic and psychiatric diseases attending an outpatient memory clinic (average age 50.7 years, SD 17.0; average education 7.8 years, SD 4.9) was followed over 18 months. Participants were challenged to use a Web-based cognitive training system, "COGWEB", on a daily basis, and fulfilled at least four weeks of training supervised remotely. Additionally, 11 patients attended face-to-face sessions. RESULTS: The average duration of continuous cognitive training was 18.8 weeks (SD 18.9). Each patient performed on average 363.5 minutes/week (SD 136.6). At 6-month follow-up, 82.8% complied with their treatment plan. The average proportion of complete weeks was 0.75 (SD 0.22). Patients with dementia trained more intensively (444.6 minutes/week), followed by patients with static brain lesion (414.5 minutes/week; P=.01). The group that held face-to-face sessions performed more training overall (481.4 vs 366.9 minutes/week), achieving a stronger expression and statistical significance in the last week of training (652.6 versus 354.9 minutes/week, P=.027). CONCLUSIONS: Overall, the weekly training intensity was high. Patients with dementia and static lesions performed more cognitive training. Face-to-face sessions were associated with higher intensities. The combination of classical methods with information technology systems seems to ensure greater training intensity.