Generation of two gene edited iPSC-lines carrying a DOX-inducible NGN2 expression cassette with and without GFP in the AAVS1 locus.

Neurog2 is the gene encoding the neuronal transcription factor NGN2, which can convert stem cells into functional neurons in a fast and efficient way. Here we report the generation of two iPS cell lines, where DOX inducible constructs of neurog2 either without or with T2A-eGFP were inserted into the safe-site locus AAVS1. These iPS cell lines, BIONi010-C-13 and BIONi010-C-15, respectively, stay pluripotent without DOX but differentiate to (GFP positive) neurons when DOX is added without the need of differentiation factors.

Chaotic motion of localized structures.

Mobility properties of spatially localized structures arising from chaotic but deterministic forcing of the bistable Swift-Hohenberg equation are studied and compared with the corresponding results when the chaotic forcing is replaced by white noise. Short structures are shown to possess greater mobility, resulting in larger root-mean-square speeds but shorter displacements than longer structures. Averaged over realizations, the displacement of the structure is ballistic at short times but diffusive at larger times. Similar results hold in two spatial dimensions. The effects of chaotic forcing on the stability of these structures is also quantified. Shorter structures are found to be more fragile than longer ones, and their stability region can be displaced outside the pinning region for constant forcing. Outside the stability region the deterministic fluctuations lead either to the destruction of the structure or to its gradual growth.

Ecological study on needs and cost of treatment for dental caries in schoolchildren aged 6, 12, and 15 years: Data from a national survey in Mexico.

To determine the treatment needs and the care index for dental caries in the primary dentition and permanent dentition of schoolchildren and to quantify the cost of care that would represent the treatment of dental caries in Mexico.A secondary analysis of data from the First National Caries Survey was conducted, which was a cross-sectional study conducted in the 32 states of Mexico. Based on dmft (average number of decayed, extracted, and filled teeth in the primary dentition) and DMFT (average number of decayed, extracted, and filled teeth in permanent dentition) information, a treatment needs index (TNI) and a caries care index (CI) were calculated.At age 6, the TNI for the primary dentition ranged from 81.7% to 99.5% and the CI ranged from 0.5% to 17.6%. In the permanent dentition, the TNI ranged from 58.8% to 100%, and the CI ranged from 0.0% to 41.2%. At age 12, the TNI ranged from 55.4% to 93.4%, and the CI ranged from 6.5% to 43.4%. At age 15, the TNI ranged from 50.4% to 98.4%, and the CI ranged from 1.4% to 48.3%. The total cost of treatment at 6 years of age was estimated to range from a purchasing power parity (PPP) of USD $49.1 to 287.7 million in the primary dentition, and from a PPP of USD $3.7 to 24 million in the permanent dentition. For the treatment of the permanent dentition of 12-year-olds, the PPP ranged from USD $13.3 to 85.4 million. The estimated cost of treatment of the permanent dentition of the 15-year-olds ranged from a PPP of USD $10.9 to 70.3 million. The total estimated cost of caries treatment ranged from a PPP of USD $77.1 to 499.6 million, depending on the type of treatment and provider (public or private).High percentages of TNI for dental caries and low CI values were observed. The estimated costs associated with the treatment for caries have an impact because they represent a considerable percentage of the total health expenditure in Mexico.

Front depinning by deterministic and stochastic fluctuations: A comparison.

Driven dissipative many-body systems are described by differential equations for macroscopic variables which include fluctuations that account for ignored microscopic variables. Here, we investigate the effect of deterministic fluctuations, drawn from a system in a state of phase turbulence, on front dynamics. We show that despite these fluctuations a front may remain pinned, in contrast to fronts in systems with Gaussian white noise fluctuations, and explore the pinning-depinning transition. In the deterministic case, this transition is found to be robust but its location in parameter space is complex, generating a fractal-like structure. We describe this transition by deriving an equation for the front position, which takes the form of an overdamped system with a ratchet potential and chaotic forcing; this equation can, in turn, be transformed into a linear parametrically driven oscillator with a chaotically oscillating frequency. The resulting description provides an unambiguous characterization of the pinning-depinning transition in parameter space. A similar calculation for noise-driven front propagation shows that the pinning-depinning transition is washed out.

Second update of the International Registry of HLA Epitopes. I. The HLA-ABC Epitope Database.

The International Registry of HLA Epitopes (http://www.epregistry.com.br) is a website-based resource for HLA epitopes important in transplant rejection and platelet transfusion refractoriness. Its primary goal is to document epitopes that are verified experimentally with specific antibodies. Such epitopes can be defined by single eplets and by eplets paired with certain polymorphic residues within a 15-Å radius, the dimension of the corresponding structural epitope. This report is an update of the HLA-ABC repertoire including descriptions of 72 antibody-verifications of epitopes defined by eplets and/or eplet pairs. The newly updated version 2.0 EpRegistry shows also the polymorphic residue compositions of structural epitopes corresponding to eplets shared between groups of alleles. At present, 151 eplets have not been antibody-verified, and we ranked them with a so-called ElliPro score as a potential predictor of immunogenicity. Sixty eplets with low ElliPro scores might be considered non-epitopes incapable of inducing specific antibodies.

Spontaneous motion of localized structures induced by parity symmetry breaking transition.

We consider a paradigmatic nonvariational scalar Swift-Hohenberg equation that describes short wavenumber or large wavelength pattern forming systems. This work unveils evidence of the transition from stable stationary to moving localized structures in one spatial dimension as a result of a parity breaking instability. This behavior is attributed to the nonvariational character of the model. We show that the nature of this transition is supercritical. We characterize analytically and numerically this bifurcation scenario from which emerges asymmetric moving localized structures. A generalization for two-dimensional settings is discussed.

Nonvariational mechanism of front propagation: Theory and experiments.

Multistable systems exhibit a rich front dynamics between equilibria. In one-dimensional scalar gradient systems, the spread of the fronts is proportional to the energy difference between equilibria. Fronts spreading proportionally to the energetic difference between equilibria is a characteristic of one-dimensional scalar gradient systems. Based on a simple nonvariational bistable model, we show analytically and numerically that the direction and speed of front propagation is led by nonvariational dynamics. We provide experimental evidence of nonvariational front propagation between different molecular orientations in a quasi-one-dimensional liquid-crystal light valve subjected to optical feedback. Free diffraction length allows us to control the variational or nonvariational nature of this system. Numerical simulations of the phenomenological model have quite good agreement with experimental observations.

p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: A study of 208 cases.

BACKGROUND: The use of p16 and p53 as biomarkers of malignant transformation of oral epithelial dysplasia (OED) and biological behavior of oral squamous cell carcinoma (OSCC) is controversial. AIM: To determine the immunoexpression of p16 and p53 in OED and OSCC and to establish their possible relation to histopathological grading of OED/OSCC. MATERIALS AND METHODS: Ninety-six OEDs (40 mild, 36 moderate, and 20 severe dysplasia); and 112 OSCCs (64 well-differentiated, 38 moderately differentiated, and 10 poorly differentiated) coming from archives of four centers of oral pathology were included. Histological slides from all cases were processed with immunohistochemical technique using anti-p53 and anti-p16 antibodies. The intensity of the immunoreactivity were classified using the ImageLab®MCM systemas follows: <60 mild, >60-<90 moderate, and >90 strong. Forstatistical purposesa χ2 test (P < 0.05) was performed. RESULTS: Severe dysplasia show highest relative frequency of p16-positive (35.5%), whereas p53 is associated with mild dysplasia (P = 0.04). Moderately differentiated OSCC had larger relative frequency of p16-positive and p53-positive cases (47.3% both circumstances) (P > 0.05). Statistical association of p16-positive and p53-positive cells to basal stratum of OED (P = 0.0008; P = 0.0000, respectively) and p16-positive cells and p53-positive cells to perivascular zone of OSCC (P = 0.001; P = 0.0000, respectively) was found. CONCLUSIONS: p16 and p53 could be not specific enough to identify patients suffering OED with high risk to malignancy; however, the evaluation of the presence of p16 and p53 in the tumoral invasive front of OSCC could contribute to establish the tumor progression.

Development of a Scalable, High-Throughput-Compatible Assay to Detect Tau Aggregates Using iPSC-Derived Cortical Neurons Maintained in a Three-Dimensional Culture Format.

Tau aggregation is the pathological hallmark that best correlates with the progression of Alzheimer's disease (AD). The presence of neurofibrillary tangles (NFTs), formed of hyperphosphorylated tau, leads to neuronal dysfunction and loss, and is directly associated with the cognitive decline observed in AD patients. The limited success in targeting ß-amyloid pathologies has reinforced the hypothesis of blocking tau phosphorylation, aggregation, and/or spreading as alternative therapeutic entry points to treat AD. Identification of novel therapies requires disease-relevant and scalable assays capable of reproducing key features of the pathology in an in vitro setting. Here we use induced pluripotent stem cells (iPSCs) as a virtually unlimited source of human cortical neurons to develop a robust and scalable tau aggregation model compatible with high-throughput screening (HTS). We downscaled cell culture conditions to 384-well plate format and used Matrigel to introduce an extra physical protection against cell detachment that reduces shearing stress and better recapitulates pathological conditions. We complemented the assay with AlphaLISA technology for the detection of tau aggregates in a high-throughput-compatible format. The assay is reproducible across users and works with different commercially available iPSC lines, representing a highly translational tool for the identification of novel treatments against tauopathies, including AD.

Eigencentrality based on dissimilarity measures reveals central nodes in complex networks.

One of the most important problems in complex network's theory is the location of the entities that are essential or have a main role within the network. For this purpose, the use of dissimilarity measures (specific to theory of classification and data mining) to enrich the centrality measures in complex networks is proposed. The centrality method used is the eigencentrality which is based on the heuristic that the centrality of a node depends on how central are the nodes in the immediate neighbourhood (like rich get richer phenomenon). This can be described by an eigenvalues problem, however the information of the neighbourhood and the connections between neighbours is not taken in account, neglecting their relevance when is one evaluates the centrality/importance/influence of a node. The contribution calculated by the dissimilarity measure is parameter independent, making the proposed method is also parameter independent. Finally, we perform a comparative study of our method versus other methods reported in the literature, obtaining more accurate and less expensive computational results in most cases.

Characterization of Aspergillus species on Brazil nut from the Brazilian Amazonian region and development of a PCR assay for identification at the genus level.

BACKGROUND: Brazil nut is a protein-rich extractivist tree crop in the Amazon region. Fungal contamination of shells and kernel material frequently includes the presence of aflatoxigenic Aspergillus species from the section Flavi. Aflatoxins are polyketide secondary metabolites, which are hepatotoxic carcinogens in mammals. The objectives of this study were to identify Aspergillus species occurring on Brazil nut grown in different states in the Brazilian Amazon region and develop a specific PCR method for collective identification of member species of the genus Aspergillus. RESULTS: Polyphasic identification of 137 Aspergillus strains isolated from Brazil nut shell material from cooperatives across the Brazilian Amazon states of Acre, Amapá and Amazonas revealed five species, with Aspergillus section Flavi species A. nomius and A. flavus the most abundant. PCR primers ASP_GEN_MTSSU_F1 and ASP_GEN_MTSSU_R1 were designed for the genus Aspergillus, targeting a portion of the mitochondrial small subunit ribosomal RNA gene. Primer specificity was validated through both electronic PCR against target gene sequences at Genbank and in PCR reactions against DNA from Aspergillus species and other fungal genera common on Brazil nut. Collective differentiation of the observed section Flavi species A. flavus, A. nomius and A. tamarii from other Aspergillus species was possible on the basis of RFLP polymorphism. CONCLUSIONS: Given the abundance of Aspergillus section Flavi species A. nomius and A. flavus observed on Brazil nut, and associated risk of mycotoxin accumulation, simple identification methods for such mycotoxigenic species are of importance for Hazard Analysis Critical Control Point system implementation. The assay for the genus Aspergillus represents progress towards specific PCR identification and detection of mycotoxigenic species.

Gendered differences in the predictors of sexual initiation among young adults in Cebu, Philippines.

PURPOSE: Social environment and family context exert substantial influence on adolescent sexual behaviors. These influences are especially important to examine in countries undergoing rapid demographic and social change. This study employs unique, intergenerational and longitudinal data (1998-2009) to examine the effects of parental, peer, and household influences on sexual initiation among young adults in Cebu, Philippines. METHODS: Intergenerational and longitudinal cohort data from the 1998 Cebu Longitudinal Health and Nutrition Survey (CLHNS) are analyzed to examine the effects of household, peer, family, and young adults' sexual attitudes on age at first sex by 2009 among young men and women. Gender-stratified Cox proportional hazards models and Cox regression models are used to model time to first sex. RESULTS: Household, family, peer, and individual characteristics have disparate influences on sexual initiation among Filipino boys and girls. Boys' sexual initiation was positively associated with urbanicity, household wealth, and the presence of a family member working abroad, whereas for girls, these variables had no significant effects. Unique effects were also found for girls-mother's education was negatively associated, and girls' number of siblings was positively associated, with higher hazards of sex. Additionally, the effects of some variables on the occurrence of first sex differed across time, indicating that boys and girls may be differentially influenced by contextual characteristics across adolescence. CONCLUSIONS: Amid substantial sociodemographic changes and persistence of traditional gender norms, this study highlights the importance of examining the unique influences and intersections of gender and context on sexual initiation in the Philippines.

Waist circumference and the risk of hypertension and prediabetes among Filipino women.

OBJECTIVES: To examine waist circumference as a risk factor for having hypertension only, impaired fasting glucose only, or both hypertension and impaired fasting glucose, and assess whether the associations vary according to overweight status. Furthermore, optimal cut-offs for waist circumference in overweight women and non-overweight women were explored. DATA AND METHODS: Data from 1,871 women aged 35-68 years in the 2005 Cebu Longitudinal Health and Nutrition Survey were used. Multinomial logistic regressions were used to model how waist circumference influenced the likelihood of having the three illness categories compared to having neither condition. Waist circumference cut-offs were explored using receiver operating characteristic analysis. RESULTS: Adjusted for age and other confounders, each cm increase in waist circumference increased the odds of hypertension by 5 % for non-overweight women and 3 % for overweight women; impaired fasting glucose by 9 and 3 % for non-overweight and overweight women, respectively; and hypertension and impaired fasting glucose by 17 % among non-overweight versus 9 % for overweight women. Waist circumference cut-offs for non-overweight women were lower than overweight women. CONCLUSION: Waist circumference was significantly associated with impaired fasting glucose and both hypertension and impaired fasting glucose, and the associations vary by overweight status.

White matter loss in a mouse model of periventricular leukomalacia is rescued by trophic factors.

Periventricular leukomalacia (PVL) is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME) leads to abnormal oligodendrocytes (OLs), myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1) promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA). Comparing lesions produced by NMDA alone and those produced by NMDA + TSC1 we found that: NMDA affected survival and reduced migration of OL progenitors (OLPs). In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult. Olig2-mRNA expression showed 52% OLP survival in mice receiving a NMDA injection and increased to 78% when TSC1 + NMDA were injected simultaneously and ventricular size was reduced by TSC1. Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection. Thus, white matter loss after excitotoxicity can be partially rescued as TSC1 conferred neuroprotection to preexisting OLP and regeneration via OLP proliferation. Furthermore, we showed that early TSC1 administration maximizes neuroprotection.

Old ideals and new realities: the changing context of young people's partnerships in Cebu, Philippines.

The Philippines has experienced rapid sociodemographic changes in recent years, with implications for young people. This study combines quantitative and qualitative data from Metro Cebu to assess the timing and predictors of young people's partnerships, as well as the context in which these partnerships are occurring. The majority of young people (54%) had premarital sex, though this pattern varied by gender. Wealthier, urban young men, and women with less education and lower reported religiosity, were more likely to have premarital sex. Engagement in risk behaviours was predictive of premarital sex for both males and females. The qualitative data contextualise the circumstances under which young people engage in sex and form partnerships and illustrate how sociocultural norms contribute to gender differences in partnership patterns. Given the 'new' realities of young Filipinos' lives, targeted efforts to support the transition to adulthood are needed to avert potentially adverse life events.

Socioeconomic, sociodemographic, and clinical variables associated with root caries in a group of persons age 60 years and older in Mexico.

AIM: To determine the prevalence of root caries and the root caries index in a population of older Mexicans, and its relationship to socioeconomic, sociodemographic and dental factors. METHODS: We carried out a cross-sectional study in 85 persons 60 years and older living either in long-term care facilities, or independently and attending an elder day-care group. Each subject underwent an oral examination, performed by a trained and standardized dentist, to determine the root caries index and other clinical variables. Questionnaires were administered to collect socioeconomic, sociodemographic and hygiene data. Statistical analyses were performed using non-parametric tests. RESULTS: The prevalence of root caries was 96.5%. The root caries index was 37.7% ± 21.7%. Statistically significant differences (P < 0.05) of root caries index were observed across residential arrangements and marital statuses, and were higher in publicly funded long-term care and among single subjects (P < 0.05). Those who had poor hygiene had more root caries (P < 0.05); persons with a low level of schooling and who brushed their teeth less frequently also showed a difference (P < 0.05). CONCLUSIONS: The prevalence of root caries was very high. The type of long-term care, marital status, schooling and oral hygiene were associated with a higher root caries index. Oral health programs and preventive caries interventions are needed for this age group in general; targeted strategies may be better focused if sociodemographic profiles are used to characterize high need groups.

Alteration of the nuclear pore complex in Ca(2+)-mediated cell death.

Cell death requires coordinated intracellular signalling before disassembly of cell architecture by degradative enzymes. Although the death signalling cascades that involve the mitochondria, the ER and the plasma membrane have been extensively characterized, only a handful of studies have examined the functional and structural alterations of the nuclear pore complex (NPC) during neuronal death. Here, we show that during excitotoxic neuronal degeneration calpains redistributed across the nuclear envelope and mediated the degradation of NPC components causing altered permeability of the nuclear membrane. In primary dissociated neurons, simultaneous recording of cytosolic [Ca(2+)] and localization of fluorescent proteins showed that the onset of Ca(2+) overload signalled a progressive increase in the diffusion of small reporter molecules across the nuclear envelope. Later, calpain-mediated changes in nuclear pore permeability allowed accumulation of large proteins in the nucleus. Further, in a model of excitotoxic neuronal degeneration in Caenorhabditis elegans, we found similar nuclear changes and redistribution of fluorescent probes across the nuclear membrane in dying neurons. Our findings strongly suggest that increased leakiness of the nuclear barrier affects nucleocytoplasmic transport, alters the localization of proteins across the nuclear envelope and it is likely to be involved in Ca(2+)-dependent cell death, including ischemic neuronal demise.

The impact of orthodontic treatment on normative need. A case-control study in Peru.

OBJECTIVE: To assess the impact of previously provided orthodontic treatment on the normative need in a sample of young adult Peruvians. METHODS: Six hundred and thirty five freshmen, representative of all first year students registering in 2002 at a private university in Lima, were randomly screened to obtain 63 cases and 126 controls. A case was defined as having a definite orthodontic treatment need determined by the DAI and IOTN indices simultaneously. A control was defined as having no need of orthodontic treatment based on both indices. Students were also asked if they had previously undergone any orthodontic treatment. Binary logistic regression was used for the statistical analysis. RESULTS: Sex, age and socioeconomic status of the students were not statistically associated with normative orthodontic treatment need (p = 0.258, 0.556 and > or = 0.272 respectively). The percentage of students with a previous history of orthodontic treatment was similar between the cases and the controls (14.3 per cent and 11 .9 per cent respectively). There were no statistically significant associations between the variables. CONCLUSIONS: The impact of previously provided orthodontic treatment on the current normative need of young adults was limited. Properly designed studies are required to assess the reasons for these findings.

Síndrome REM associada a lúpus eritematoso sistêmico e hipotireoidismo / REM syndrome associated with systemic lupus erythematosus and hypotiroidism

A mucinose eritematosa reticulada é síndrome crônica e rara de etiologia desconhecida que afeta adultos jovens e de meia idade, principalmente do sexo feminino. Clinicamente é caracterizada por máculas eritematosas reticulares, pápulas e placas localizadas de forma simétrica em área central do tórax e dorso. Em aproximadamente 20 por cento dos casos pode estar associada com várias doenças, especialmente auto-imunes. Os autores apresentam um caso de mucinose eritematosa reticulada associada a lúpus eritematoso sistêmico e hipotireoidismo.

Reticular erythematous mucinosis is a chronic and rare syndrome of unknow aetiology that affects young adult and midle-aged women. Clinical presentation is characterized by macular and reticulated erythema, papula and plaques on the central chest and upper back of simmetrical form. In approximately 20 percent of the cases may be associated with a variety of disorders, especially auto-immune diseases. The authors present a case of reticular erythematous mucinoses associated with systemic lupus erythematosus and hypothiroidism.

[Evaluation of the diagnostic value of a Spanish adaptation of the Buschke Memory Impairment Screen in the detection of dementia and cognitive impairment]. / Evaluacion de la utilidad diagnostica de una adaptacion espanola del Memory Impairment Screen de Buschke para detectar demencia y deterioro cognitivo.

INTRODUCTION: Screening tests for dementia are a fundamental tool in specialist consultation and primary care. The instruments currently used are time-consuming and the diagnostic performance they offer is rather poor. The original version of the Buschke Memory Impairment Screen (MIS) is a quick simple test with high discriminatory power. AIMS: Our aim was to validate a Spanish version of the MIS in specialist consultation. PATIENTS AND METHODS: We conducted a prospective study in 91 subjects aged over 60 who visited the outpatient department for cognitive evaluation. All the patients received a similar diagnostic evaluation and the MIS was administered as a blind test. This Spanish version of the MIS was produced by means of a cross-cultural adaptation. RESULTS: The area below the ROC curve for dementia on the MIS was 0.92, with a similar result for cognitive deterioration (CD). A cut-off score of 4 or less offered a sensitivity rate of 91.9% (CI 95%: 83.4-96.4%) and a specificity level of 81.0% (CI 95%; 70.3-88.6%) for the detection of CD. Likewise, a cut-off score of 3 or below presented a sensitivity rate of 96.1% (CI 95%: 85.7-99.3%) and a degree of specificity of 72.6% (CI 95%: 63.2-80.3%) for the detection of dementia. Interobserver and test-retest reliability (0.85 and 0.81, respectively) were adequate. CONCLUSIONS: This version of the Buschke MIS offers a high level of discriminatory power both for dementia and for CD, as well as an adequate degree of inter and intraobserver reliability within the context of a specialist consultation. Because it is quick (less than 4 minutes) and simple to administer, MIS represents a reasonable alternative to other screening methods.