Oxidative stress in the ovaries of mice chronically exposed to a low lead concentration: A generational approach.

Lead (Pb) is a heavy metal that alters the oxidation-reduction balance, affecting reproductive health and transfer during pregnancy and lactation. However, the multigenerational impact of exposure to low concentrations of Pb on mammalian ovaries has not been assessed. This study evaluated general parameters, histology, redox state (RS), protein carbonylation (PC), lipid peroxidation (LP), and hormone concentrations in the ovaries of mice (CD1® ICR) of three successive generations with both unigenerational (E1) and multigenerational (E2) exposure to 0.2 ppm lead acetate through the drinking water and a control group. Body weight, food consumption, the number of born pups, and their weight after weaning were not significantly affected by Pb exposure in E1 and E2. However, the ovaries of three successive generations of the E1 group, in which only the F0 was exposed, showed alterations in the ovarian histoarchitecture, increase in follicular atresia, decrease in the number of available follicles, and a significant RS and PC elevation that were surprisingly similar to those observed in the E2 group. LP increased in the second generation of E1 and E2, while hormone concentration was not altered. This is the first demonstration that exposure to low concentration of Pb induces multigenerational histological alterations and oxidative stress in mouse ovaries, that the termination of this exposure does not ensure the safety of later generations and that the lack of modifications in general parameters may facilitate the silent development of pathologies that affect ovarian health.

Caregiver knowledge of obstructive sleep apnoea in Down syndrome.

BACKGROUND: Down syndrome (DS) population has a very high prevalence of obstructive sleep apnoea (OSA), but this remains underdiagnosed. Hence, we aimed to evaluate caregiver's knowledge of OSA and related sociodemographic factors that could contribute to OSA screening patterns in this population. METHODS: An online survey though the LuMind IDSC Foundation focused on OSA diagnosis, treatments and the number of sleep studies performed. Data were compared between subjects born before and after the American Academy of Pediatrics (AAP) recommendations for OSA screening. RESULTS: Of the caregivers, 724 (parents 96.3%), responded to the survey. The median [interquartile (IQR)] age of the subjects with DS was 12 [20;7] years. The majority (84.3%) had sleep apnoea diagnosis, and half of them were initially referred for a sleep study due to disturbed sleep symptoms. Only 58.7% of the responders were aware of the AAP recommendations. This was linked to higher socioeconomic and/or educational level and to an earlier OSA diagnosis. The median (IQR) age of OSA diagnosis was lowered after the AAP guidelines publication compared with before its publication (3 [4;2] years vs. 10 [18;5] years, P < 0.000). Adenotonsillectomy (81.9%) and continuous positive airway pressure (61.5%) were the most commonly prescribed treatments. Few had discussed other new therapies such as hypoglossal nerve stimulation (16.0%). Only 16.0% of the subjects repeated the sleep study to monitor OSA with ageing, and 30.2% had to wait more than 4 years between studies. CONCLUSIONS: This study reinforces the need to improve OSA knowledge of caregivers and clinicians of individuals with DS to promote an earlier diagnosis and optimal treatment of OSA in this population.

Making thirsty cities sustainable: A nexus approach for water provisioning in Quito, Ecuador.

In view of accelerated climate change and urban demographics, balancing human and ecosystem needs for water resources is a critical environmental challenge of global significance. Since water, agriculture, health, and energy are inextricably linked, sustainable development goals (SDGs) actions in one policy area commonly have impacts on the others, as well as on the ecosystems that natural resources and human activities ultimately depend upon. Managing urban water supply systems therefore requires a nexus approach that integrates goals across sectors, reduces the risk that SDG actions will undermine one another, and ensures sustainable resource use. We developed a transdisciplinary methodological framework based on a Pareto frontier analysis to define the sustainable solutions of a multi-objective optimization among four competing criteria, water provision, water quality, energy cost, and biodiversity conservation. The study was applied to three mountainous headwater basins in the Ecuadorian Andes, which provide around 30% of Quito's total water supply. We found that an optimized management of water intake structures would meet current consumption needs while reducing the probability of emergence of water pathogens and limiting the impact on aquatic biodiversity by 30% and 9% respectively, without any increase in energy costs for pumping water from other sources. Nonetheless, under future scenarios of climate change and water demand, higher energy consumption, and therefore an increase in operating costs, would be needed to meet urban demand and preserve environmental conditions. Overall, the range of Pareto optimal water supply strategies across the water-health-energy-biodiversity nexus provides valuable information for decision makers and offers support for achieving sustainable management of water resources.

Doxycycline-functionalized polymeric nanoparticles inhibit Enterococcus faecalis biofilm formation on dentine.

AIM: To evaluate in a laboratory setting the antimicrobial properties and the potential to inhibit biofilm formation of novel remineralizing polymeric nanoparticles (NPs) when applied to dentine surfaces and to ascertain the effect of the functionalization of these NPs with zinc, calcium or doxycycline. METHODOLOGY: The antimicrobial activity and inhibition of biofilm formation of polymeric NPs were analysed on human dentine blocks that were infected with Enterococcus faecalis before or after application of NPs. LIVE/DEAD ® testing under Confocal Laser Scanning Microscopy and bacterial culturing were employed to analyse biofilm biovolume and bacterial viability. Field Emission Scanning Electron Microscopy was also employed to assess biofilm morphology. One-way anova with Welch's correction and post hoc comparison by the Games-Howell test were performed for comparisons between groups. RESULTS: The un-functionalized NPs displayed the greatest antimicrobial activity against E. faecalis biofilms as they provided the lowest biovolume (3865.7 ± 2926.97 µm3 ; P < 0.001) and the highest dead/injured cells percentage (79.93 ± 18.40%; P < 0.001), followed by Dox-NPs (biovolume: 19,041.55 ± 17,638.23 µm3 , dead/injured cells: 45.53 ± 26.50%; P < 0.001). Doxycycline-loaded NPs had the largest values of inhibition of biofilm formation with the lowest biofilm biovolume (8517.65 ± 7055.81 µm3 ; P < 0.001) and a high dead/injured bacterial percentage (68.68 ± 12.50%; P < 0.001). Un-functionalized NPs did not reduce biomass growth (P > 0.05), but attained the largest percentage of compromised cells (93 ± 8.23%; P < 0.001), being able to disrupt biofilm formation. It also produced occlusion of dentinal tubules, potentially interfering with bacterial tubule penetration. CONCLUSIONS: A new generation of bioactive nano-fillers (doxycycline-functionalized polymeric NPs) had antibacterial activity and occluded dentinal tubules. Incorporating these NPs into endodontic sealers may have the potential to enhance the outcome of root canal treatment.

Antimicrobial effect of nanostructured membranes for guided tissue regeneration: an in vitro study.

OBJECTIVE: The purpose of this in vitro study was to evaluate the antibacterial effect of a novel non-resorbable, bioactive polymeric nanostructured membrane (NMs), when doped with zinc, calcium and doxycycline. METHODS: A validated in vitro subgingival biofilm model with six bacterial species (Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) was used. The experimental NMs, with and without being doped with doxycycline, calcium and zinc, were placed on hydroxyapatite (HA) discs. As positive control membranes, commercially available dense polytetrafluoroethylene (d-PTFE) membranes were used and, as negative controls, the HA discs without any membrane. The experimental, positive and negative control discs were exposed to a mixed bacterial suspension, at 37 °C under anaerobic conditions, during 12, 24, 48 and 72 h. The resulting biofilms were analyzed through scanning electron microscopy (SEM), to study their structure, and by quantitative polymerase chain reaction (qPCR), to assess the bacterial load, expressed as colony forming units (CFU) per mL. Differences between experimental and control groups were evaluated with the general linear model and the Bonferroni adjustment. RESULTS: As shown by SEM, all membrane groups, except the NMs with doxycycline, resulted in structured biofilms from 12-72 hours. Similarly, only the membranes loaded with doxycycline demonstrated a significant reduction in bacterial load during biofilm development, when compared with the control groups (p < 0.001). SIGNIFICANCE: Doxycycline-doped nanostructured membranes have an impact on biofilm growth dynamics by significant reducing the bacterial load.

Statin Short-term Inhibition of Insulin Sensitivity and Secretion During Acute Phase of ST-Elevation Myocardial Infarction.

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.

Silver-loaded nanoparticles affect ex-vivo mechanical behavior and mineralization of dentin.

BACKGROUND: The aim was to evaluate the effect of silver loaded nanoparticles (NPs) application on the triboscopic, crystallographic and viscoelastic properties of demineralized dentin. Polymethylmetacrylate-based NPs and Ag loaded NPs were applied on demineralized dentin. MATERIAL AND METHODS: Treated and untreated surfaces were probed by a nanoindenter to test viscoelasticity, and by atomic force microscopy to test nanoroughness and collagen fibril diameter. X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging were also used. RESULTS: Dentin treated with Ag-NPs attained the lowest complex modulus, and the highest tan delta values after 7 days of storage. Dentin treated with undoped-NPs achieved the lowest nanoroughness and the greatest collagen bandwidths among groups. Crystals were identified as hydroxyapatite with the highest crystallographic maturity and crystallite size in dentin treated with undoped-NPs. Texture increased in all samples from 24 h to 7 d, except in dentin surfaces treated with Ag-NPs at 310 plane. Polyhedral, block-like, hexagonal or plate-like shaped apatite crystals constituted the bulk of minerals in dentin treated with Ag-NPs, after 7 d. Polyhedral or rounded/drop-like, and polymorphic in strata crystal apatite characterized the minerals when undoped-NPs were used, with more crystalline characteristics after 7 d than that found when Ag-NPs were applied. Ag-NPs application did not improve the mechanical performance of dentin and did not produce dentin remineralization. However, energy was dissipated through the dentin without showing stress concentration; contrary was occurring at dentin treated with undoped-NPs, that provoked bridge-like mineral deposits at the dentin surface. CONCLUSIONS: Ag-NPs application did not enhance the mechanical properties of cervical dentin, though the energy dissipation did not damage the dentin structure. Remineralization at dentin was not produced after Ag-NPs application, though improved crystallinity may lead to increase stability of the apatite that was generated at the dentin surface.

Antibacterial effects of polymeric PolymP-n Active nanoparticles. An in vitro biofilm study.

OBJECTIVE: to study the antibacterial effect of polymeric PolymP-n Active nanoparticles using an in vitro subgingival biofilm model. METHODS: Hydroxyapatite discs coated with five modalities of nanoparticles (NPs): NPs, NPs doped with zinc, calcium, silver and doxycycline, PBS as control, and Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied in a static in vitro biofilm model (12, 24, 48, and 72h). Nano-roughness of the different disc surfaces (SRa, in nm) and morphological characteristic of the biofilms (thickness (µm) and bacterial viability) were studied by different microscopy modalities. Quantitative Polymerase Chain Reaction was used to assess the effect of the nanoparticles on the bacterial load (colony forming unit per milliliter) (CFUmL-1). Analysis of variance and post-hoc testing with T3 Dunnett́s, and Student Newman Keuls correction was used. Results were considered statistically significant at p<0.05. RESULTS: Surfaces containing the different nanoparticles showed significant increments in roughness when compared to controls (p<0.05). A similar biofilm formation and dynamics was observed, although reductions in bacterial viability were detected in biofilms in contact with the different nanoparticles, more pronounced with silver and doxycycline NPs. Doxycycline-NPs biofilms resulted in unstructured biofilm formation and significantly lower number of the six species when compared with the other nanoparticles specimens and controls (p<0.001 in all cases). SIGNIFICANCE: Polymeric PolymP-n Active nanoparticles when combined with silver and doxycycline showed a significant antibacterial effect when tested in an in vitro subgingival biofilm model.

A zinc-doped endodontic cement facilitates functional mineralization and stress dissipation at the dentin surface.

BACKGROUND: The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. MATERIAL AND METHODS: Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (δ). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. RESULTS: After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan δ values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. CONCLUSIONS: Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan δ after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface.

Ion-modified nanoparticles induce different apatite formation in cervical dentine.

AIM: To investigate if crystallinity and ultrastructure are modified when cervical dentine is treated with four different nanogels-based solutions for remineralizing purposes. METHODOLOGY: Experimental nanogels based on polymeric nanoparticles (NPs) and zinc, calcium or doxycycline-loaded NPs were applied to citric acid etched dentine to facilitate the occlusion of tubules and the mineralization of the dentine surface. Dentine surfaces were studied by X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging. RESULTS: Crystals at the dentine surface were identified as hydroxyapatite with the highest crystallographic maturity and crystallite size in dentine treated with Zn-NPs-based gel. Texture increased in all samples from 24 h to 7 days, except in dentine surfaces treated with Zn-NPs gel. Polyhedral, plate-like and drop-like shaped apatite crystals constituted the bulk of minerals in dentine treated with Zn-NPs gel, after 7 days. Polymorphic, cubic and needle-like shaped crystals distinguished minerals, with more amorphous characteristics in dentine treated with Ca-NPs gel after 7 days than that found when Zn-NPs were applied. Doxycycline-NPs produced the smallest crystallites with poor crystallinity, maturity and chemical stability. CONCLUSIONS: Crystalline and amorphous phases of newly formed hydroxyapatite were described in both types of dentine treated with Zn-NPs as well as Ca-NPs gels with multiple shapes of crystallites. Crystal shapes ranged from rounded/drop-like or plate-like crystals to needle-like or polyhedral and cubic apatite appearance.

Aneuploidy identification in pre-B acute lymphoblastic leukemia patients at diagnosis by Multiplex Ligation-dependent Probe Amplification (MLPA).

Three-quarters of the patients with acute lymphoblastic leukemia (ALL), show numerical or structural chromosomal alterations, which are important factors in leukemogenesis. The use of Multiplex Ligation-dependent Probes Amplification (MLPA) has been mainly limited for searching copy number alterations of genes, suggesting that MLPA could detect numerical alterations in cancer. However, the use of MLPA in pediatrics to analyze subtelomeric sequences for aneuploidy detection has not been considered in previous studies. The aim of this study was to identify aneuploidy for the first time using MLPA and correlate the results with karyotype and DNA-index (DI), from preB ALL patients. Forty-two bone marrow samples were analyzed by cytogenetics and flow cytometry to determine the DI. The chromosomal gains and/or losses were detected by the SALSA MLPA P036 Subtelomere Mix 1 probemix®. The chromosomal number matched in 36 out of 42 samples between MLPA and karyotype (R2=0.7829, p=3.7×10-10), 18/42 between MLPA and DI (R2=0.1556, p=0.023), and 20/42 between karyotype and DI (R2=0.1509, p=0.015). MLPA results correlated with karyotype and DI. The use of MLPA led us to identify a gained marker chromosome. Our results indicate that MLPA could be a useful and fast alternative tool for aneuploidy identification in pediatric leukemia.

A zinc oxide-modified hydroxyapatite-based cement facilitated new crystalline-stoichiometric and amorphous apatite precipitation on dentine.

AIM: To evaluate the remineralization ability of two endodontic sealer cements. METHODOLOGY: Mid-coronal dentine surfaces were subjected to: (i) 37% phosphoric acid (PA) or (ii) 0.5 mol L-1 ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide oxiapatite respectively. Samples were stored in simulated body fluid for 24 h or 21 days. Remineralization of the dentine surfaces were studied by Raman spectroscopy (mapping with K-means cluster and hierarchical cluster analysis) was undertaken. Nanoroughness and collagen fibril width measurements were performed with an atomic force microscopy. ANOVA and Student-Newman-Keuls test were performed (α=0.05). RESULTS: Phosphoric acid+oxiapatite promoted both the highest dentine mineralization (P < 0.05) and crystallographic maturity at the dentine surface. Noncrystalline amorphous-like apatites were also formed. Dentine treated with PA+calcypatite attained the roughest surface (P < 0.05) with minimal fibril width (P < 0.05). Cross-linking of collagen only became greater in the group PA+oxiapatite after 21 days. The maximum relative mineral concentration and structure of collagen linked to the amide I and ratio amide III/AGEs was obtained after using PA+calcypatite at 21-days time-point (P < 0.05). EDTA produced a lower stoichiometric hydroxyapatite (P < 0.05) with decreased maturity, at the expense of carbonate band widening, although it favoured the nucleation of carbonated calcium phosphate. CONCLUSIONS: Dentine surfaces treated with PA+oxiapatite attained the highest dentine remineralization with both crystalline-stoichiometric and amorphous apatites, at 21 days. EDTA conditioning facilitated amorphous-bulk mineral precipitation. The amorphization was more intense after using oxiapatite and provided an ion-rich environment favouring in situ dentine remineralization.

Polyaspartic acid enhances dentine remineralization bonded with a zinc-doped Portland-based resin cement.

AIM: To ascertain whether biomimetic phosphoprotein analogues (polyaspartic acid (PAS) and sodium trimetaphosphate (TMP)) improve bonding efficacy and dentine remineralization ability of a novel zinc-doped Portland-based resinous sealing cement. METHODOLOGY: Bonding procedures were performed on phosphoric acid-etched dentine, and several groups were established regarding biomimetic analogue application: (1) no application, (2) PAS-treated dentine and (3) dentine treated with a mixture of PAS and TMP. Raman spectroscopy and microtensile bond strength (MTBS) with fracture analysis by scanning electron microscopy were carried out. MTBS values were compared by anova, Student-Newman-Keuls and Student's t-tests (P < 0.05 and P < 0.01, respectively). RESULTS: Twenty-four hour MTBS values were not affected by the different bonding procedures. After 6 months, MTBS decreased in those groups in which the phosphoproteins analogues were not applied (P < 0.05). When PAS was applied, MTBS was maintained after 6 months (P > 0.05). The novel material bonded without primer application induced bioactive crystal (calcium carbonate and Ettringite) precipitation onto the etched dentine and augmented the degree of crystallinity at the hybrid layer. Mineral-to-matrix ratio was increased at the hybrid layer of the PAS-treated specimens; this primer was also able to catalyse dentine remineralization, without an increase in crystallinity. CONCLUSIONS: PAS application onto demineralized dentine produced an inhibition or delay of mineral phase crystallization, enhancing the remineralization potential of the Portland microfillers at the resin-dentine bonded interface.

¿De qué color vemos cuando nos enfadamos? / What color do we see when get angry?

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Guía fármacoterapeutica de amenaza de parto pretérmino / Pharmacotherapeutic guide of the risk of premature birth / Guia farmacoterapêutico do risco de parto prematuro

El parto pretérmino representa un reto terapéutico ya que su tratamiento oportuno disminuye la morbilidad y mortalidad \r\nneonatal. Afecta de 5 a 11% de todos los partos en el mundo, entre 9 y 10% en países de bajos ingresos y de 6 a 11,9% en países \r\ncon altos ingresos. Es el responsable de 70% de las muertes neonatales y 37% de las muertes en infantes así como el causante de \r\n25 a 50% de los casos de falla en el desarrollo neurológico en niños. Por lo anterior, es importante realizar un adecuado tamizaje \r\ny tratamiento de las pacientes que se encuentran en riesgo de parto pretérmino. Para ello, se realizó una guía fármacoterapeutica \r\nbasada en la mejor evidencia para su manejo.

preterm labor represents a therapeutic challenge because \r\nopportune treatment decreases neonatal morbidity and \r\nmortality. It affects 5-11% of all worldwide births. Of these \r\nbirths 9-10% occurred in low-income countries and 6-11.9% in \r\nhigh-income countries. Preterm labor is responsible for 70% \r\nof neonatal deaths and 37% of infant deaths; it causes 25-50% \r\nof the cases of neurological development failure in children. \r\nBecause of this, it is important to perform adequate screening \r\nand treatment of patients at risk for preterm delivery. A pharma\r\n-\r\nceutical guide based on the best evidence for its management \r\nwas performed.

O parto prematuro representa um desafio terapêutico, uma vez \r\nque seu tratamento oportuno diminui a morbidez e mortali\r\n-\r\ndade neonatal. Afeta de 5 a 11% de todos os partos no mundo, \r\nsendo que, entre 9 e 10% ocorrem em países de baixa renda, \r\ne de 6 a 11,9%, em países de alta renda. É responsável por 70% \r\ndas mortes neonatais e 37% das mortes em recém-nascidos, \r\nassim como é o causador de 25 a 50% dos casos de falha no \r\ndesenvolvimento neurológico em crianças. Por este motivo, \r\né importante realizar uma triagem e tratamento adequados \r\ndas pacientes que se encontram em risco de parto prematuro. \r\nPortanto, foi elaborado um guia farmacoterapêutico com base \r\nna melhor evidência para seu manuseio.

Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.

Polymer nanocarriers for dentin adhesion.

To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP- N : Active nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days' immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p < .05). Nanoparticles were effectively zinc-loaded and were shown to have a chelating effect, retaining calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be incorporated into dental adhesive systems to provide the appropriate environment in which dentin MMP collagen degradation is inhibited and mineral growth can occur.

Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease.

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer's disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined. MEASUREMENTS: Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures. RESULTS: Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk's Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship. CONCLUSION: NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD.

[A diagnostic predictive scale for urinary tract infection in febrile infants without an apparent focus]. / Escala predictiva diagnóstica de infección urinaria en neonatos febriles sin foco aparente.

INTRODUCTION: Urinary tract infection (UTI) is the most frequent bacterial infection in infants with nonspecific clinical manifestations. OBJECTIVE: To validate a predictive scale for UTI in febrile infants without apparent source and hospitalized in a neonatal unit. PATIENTS AND METHOD: A nested case-control study was conducted on 158 infants with febrile UTI, culture-confirmed, and on 346 febrile infants without apparent focus in whom UTI was ruled out, and also, hospitalized in a neonatal unit. The analysis was performed using Stata® 11. Associations were determined using odds ratio (OR) with 95% confidence interval. To find the predictive scale, multivariate analysis was performed using logistic regression and establishing major and minor criteria according to regression coefficient. Yield was calculated by sensitivity, specificity and area under ROC curve. The new predictive scale was validated by 108 new febrile neonates. RESULTS: The major criteria to predict UTI were abnormal urinalysis and Gram positive cells without centrifugation, and among the minor criteria, male, age at time of fever, previous neonatal hospitalization, abnormal temperature (38.5°C or more, persistent fever, hypothermia) and 1.7 mg/dL C reactive protein or higher, resulting positive with the presence of one mayor or three minor criteria. It showed good performance with 100% sensitivity (CI 95%:98.3-100%), 92.3% specificity (CI 95%: 85.8-98.9%) and 0.962 area under ROC (95% CI: 0.932-0.991) when validated on 108 new febrile neonates without focus. CONCLUSIONS: The new predictive scale allows predicting UTI with good yield in infants with fever without an identified source.