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.

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.

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.

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.

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.

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.

Reduced glucose uptake and Aß in brain regions with hyperintensities in connected white matter.

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (ß = 0.045) and FDG-PET (ß = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.

Zinc induces apatite and scholzite formation during dentin remineralization.

The aim of this study was to ascertain whether zinc may improve the repair ability of demineralized dentin. Dentin disks were demineralized by phosphoric acid during 15 s and immersed in artificial saliva, remineralizing solution, a zinc chloride solution and a zinc oxide solution. Dentin specimens were analyzed after 24 h and 1 month of storage. Surface morphology was assessed by atomic force and scanning electron microscopy, mechanical properties were analyzed by nanohardness testing in a TriboIndenter, and chemical changes at the surfaces were determined by X-ray diffraction, Raman and energy-dispersive elemental analyses. After phosphoric acid application, dentin was only partially demineralized. Demineralized dentin was remineralized after 24 h of storage in any of the tested solutions (nanohardness increased and hydroxylapatite formation was detected by Raman). Remineralization was maintained up to 1 month in dentin stored in remineralizing solution, zinc chloride and zinc oxide. Zinc and phosphate were important for hydroxylapatite homeostasis. Scholzite formation was encountered in dentin stored in zinc-containing solutions. Zinc might allow to reach the balance between dentin demineralization and remineralization processes.

Magnesium phosphate cements for endodontic applications with improved long-term sealing ability.

AIM: To characterize three radiopaque Magnesium Phosphate Cements (MPCs) developed for endodontic purposes. METHODOLOGY: Three experimental MPCs containing Bi2 O3 were formulated. The experimental cements, which consisted of mixtures of magnesium oxide with different phosphate salts, were characterized for setting time, injectability, porosity, compressive strength and phase composition. The long-term sealing ability of the experimental MPCs applied in single-rooted teeth as root canal filling material or as sealer in combination with gutta-percha was also assessed using a highly sensitive fluid filtration system. A mineral trioxide aggregate (MTA) cement was used as control. Statistical analysis was performed with two- or three-way analysis of variance (anova) and Tukey's test was used for comparisons. RESULTS: The addition of 10 wt% Bi2 O3 within the composition of the MPCs provided an adequate radiopacity for endodontic applications according to ISO 6876 standard. The reaction products resulting from the MPCs were either struvite (MgNH4 PO4 ·6H2 O) or an amorphous sodium magnesium phosphate. The porosity of the three MPCs ranged between 4% and 11%. The initial setting time of the experimental cements was between 6 and 9 min, attaining high early compressive strength values (17-34 MPa within 2 h). All MPC formulations achieved greater sealing ability than MTA (P < 0.05) after 3 months, which was maintained after 6 months for two of the experimental cements (P < 0.05). CONCLUSIONS: These MPCs had adequate handling and mechanical properties and low degradation rates. Furthermore, a stable sealing ability was demonstrated up to 6 months when using the cement both as root filling material and as sealer in conjunction with gutta-percha.

Imaging and cerebrospinal fluid biomarkers in the search for Alzheimer's disease mechanisms.

BACKGROUND: The pathophysiological process of Alzheimer's disease (AD) begins many years before the emergence of clinical symptoms (preclinical AD). A hypothetical biomarker progression in the pathogenesis of AD has been suggested, beginning with the deposition of amyloid-ß (Aß) and followed by increases in neurofibrillary tangles, synaptic loss, hippocampal atrophy, and lastly, cognitive impairment. OBJECTIVE: We explored the effect of several risk factors for AD on the pattern of AD biomarker expression in normal subjects. METHODS: AD biomarker evidence was examined at baseline in 96 cognitively normal elderly subjects with none or at least one of the following: ApoE4+ allele, a maternal history of AD (mFHx), sleep-disordered breathing (SDB), and longitudinal evidence of decline to mild cognitive impairment or AD (decliners) at follow-up. RESULTS: Decliners and ApoE4+ subjects presented with expected reduced cerebrospinal fluid Aß42, elevated P-tau and T-tau. In addition, decliners had fluorodeoxyglucose positron emission tomography hypometabolism in the medial temporal lobe. Individuals with mFHx demonstrated no Aß42 effect, but had elevations in P-tau and T-tau. SDB was found to be associated with elevated Aß42, P-tau and T-tau, as well as with reduced medial temporal lobe glucose metabolic rates. CONCLUSION: Our results indicate a heterogeneous biomarker expression, suggesting diversity of AD pathways in at-risk presymptomatic subjects.

[Factors associated with prolonged hospital stay in infants]. / Factores asociados a estancia hospitalaria prolongada en neonatos.

OBJECTIVE: To evaluate factors present on newborn admission to a neonatal intensive care and associated with a prolonged hospital stay. PATIENTS AND METHOD: Non-matched case-control study, with 555 infants, 111 with more than 7 days of hospital stay and 444 who stayed hospitalized between 1 and 7 days, between 2005 and 2010. Pre hospitalization maternal factors (age, pregnancy, health insurance, education, prenatal care, marital status, history of preeclampsia, prolonged rupture of membranes, chorioamnionitis infection) and neonatal ones (age at admission, gestational age, birth weight, gender, delivery practice, route of admission, Apgar and type of resuscitation) that were associated with prolonged hospital stay were analyzed. Analyses were conducted using STATA 11.0 and logistic regression in the multivariate analysis. RESULTS: Maternal factors such as prenatal care with less than 5 doctor visits (AOR 2.7, 95% CI 1.3-5.5), lack of social health insurance (AOR 1.9, 95% CI 1.4-29), pregnant three or more times (AOR 1.7, 95% CI 1.1-2.7), neonatal birth weight under 2,000 g (AOR 4.2, 95% CI 1.9-9.5), need for cardiopulmonary resuscitation (AOR 4.2, 95% CI 2-9.1), gestational age less than 36 weeks (AOR 3.9, 95% CI 2-7.7) and admission to the neonatal unit through emergency room or referral from another hospital (AOR 2.8, 95% CI 1.7-4.6) were associated with hospital stays longer than 7 days. CONCLUSIONS: In-hospital complications that affect a prolonged stay at the health center were social health insurance, maternal education and prenatal care, and these should be considered in the evaluation of the hospital care quality indicators.

[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.

Calcium-activated chloride channels do not contribute to the odorant transduction current in the marine teleost Isacia conceptionis.

This study compared the contribution of the Ca²âº-activated Cl⁻ conductance to the electroolfactogram (EOG) evoked by different odorant classes between the marine Cabinza grunt Isacia conceptionis and rainbow trout Oncorhynchus mykiss. The Ca²âº-activated Cl⁻ channel blocker niflumic acid significantly diminished odorant responses in O. mykiss, but had no effect on the EOG in I. conceptionis, supporting the notion that Ca²âº-activated Cl⁻ channels may not operate as odorant transduction current amplifiers in this marine teleost.

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.

Zinc-inhibited MMP-mediated collagen degradation after different dentine demineralization procedures.

BACKGROUND: Dentine matrix metalloproteinases (MMPs) play an important role in the dentine caries process. AIMS: To determine if MMP-mediated collagen degradation of acid-demineralized dentine may be inhibited by zinc or zinc chelators. METHODS: Human dentine specimens were demineralized by phosphoric acid (PA), ethylenediaminetetraacetic acid (EDTA), Clearfil SE Bond primer (SE), or Xeno V (XE) and stored in artificial saliva. Chlorhexidine digluconate (CHX), doxycycline, EDTA, or ZnCl(2) was added. C-terminal telopeptide determinations (ICTP) were performed by radioimmunoassay after 24 h and 4 weeks. RESULTS: Collagen degradation was prominent in PA-demineralized (ICTP values from 74.01 µg/l at 24 h to 202.46 µg/l after 4 weeks) and EDTA-demineralized dentine (ICTP values from 83.93 µg/l at 24 h to 158.82 µg/l after 4 weeks) stored in artificial saliva. Doxycycline fully blocked proteolysis. CHX and EDTA reduced collagen degradation only at 24 h. Zinc in excess strongly inhibited hydrolysis of collagen in all tested groups (ICTP values were: PA, 13.56 µg/l; EDTA, 11.21 µg/l; SE, 1.52 µg/l, and XE, 2.37 µg/l) and its effect was maintained for up to 4 weeks, except for EDTA-treated dentine (ICTP values were: PA, 40.76 µg/l; EDTA, 79.15 µg/l; SE, 5.29 µg/l, and XE, 6.38 µg/l). CONCLUSION: EDTA and CHX exerted time-limited MMP inhibition, and excess zinc served as an effective inhibitor of MMP-mediated collagen degradation in strong or mildly demineralized dentine. MMP degradation of collagen was reduced in resin-infiltrated dentine; the presence of excess zinc chloride exerted an additional protective effect.

Diagnostic criteria for apathy in clinical practice.

BACKGROUND: Apathy is an important and distressing behavioural symptom in Alzheimer's disease and in various neuropsychiatric disorders. Recently, diagnostic criteria for apathy have been proposed. OBJECTIVES: In groups of patients suffering from different neuropsychiatric diseases, (i) to estimate the prevalence of patients meeting the proposed diagnostic criteria; (ii) to estimate the concurrent validity of the criteria with the neuropsychiatric inventory (NPI) apathy item; (iii) to identify the most frequently met criteria or sub-criteria in each specific neuropsychiatric disease and (iv) to estimate the inter-observer reliability of the diagnostic criteria for apathy. METHODS: This cross-sectional, multicentric, observational study was performed on 306 patients. Each of the participating centres had to check the presence of apathy according to the diagnostic criteria for apathy in consecutive patients belonging to the following diagnoses list: Alzheimer disease (AD), mixed dementia, mild cognitive impairment (MCI), Parkinson's disease (PD), Schizophrenia (DSM-IV) and major depressive episode. In addition to the clinical interview, the assessment included the Mini Mental Score Examination (MMSE) and the NPI. At the end of the visit, clinicians were required to check the diagnostic criteria for apathy. RESULTS: Using the diagnostic criteria for apathy, the frequency of apathy was of 53% in the whole population, 55% in AD, 70% in mixed dementia, 43% in MCI, 27% in PD, 53% in schizophrenia and 94% in major depressive episode. In AD, mixed dementia, MCI and PD, the NPI apathy score was significantly higher for patient fulfilling the apathy criteria. Goal-directed cognitive activity (criteria B2-Cognition) was the most frequently observed domain followed by goal-directed behaviour (criteria B1-Behaviour) and emotion (criteria B3), respectively. Inter-rater reliability was high for the overall diagnostic (κ coefficient = 0.93; p = 0.0001) and for each criteria. CONCLUSION: This study is the first one to test the diagnostic criteria for apathy in clinical practice. Results make the diagnostic criteria useful for clinical practice and research.

The concept of FDG-PET endophenotype in Alzheimer's disease.

Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term "endophenotype" has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term "endophenotype" should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD.