Nanocarriers as Active Ingredients Enhancers in the Cosmetic Industry-The European and North America Regulation Challenges.

"Flawless skin is the most universally desired human feature" is an iconic statement by Desmond Morris. Skin indicates one´s health and is so important that it affects a person's emotional and psychological behavior, these facts having propelled the development of the cosmetics industry. It is estimated that in 2023, this industry will achieve more than 800 billion dollars. This boost is due to the development of new cosmetic formulations based on nanotechnology. Nanocarriers have been able to solve problems related to active ingredients regarding their solubility, poor stability, and release. Even though nanocarriers have evident benefits, they also present some problems related to the high cost, low shelf life, and toxicity. Regulation and legislation are two controversial topics regarding the use of nanotechnology in the field of cosmetics. In this area, the U.S. FDA has taken the lead and recommended several biosafety studies and post-market safety evaluations. The lack of a global definition that identifies nanomaterials as a cosmetic ingredient is a hindrance to the development of global legislation. In the EU, the legislation regarding the biosafety of nanomaterials in cosmetics is stricter. "The cost is not the only important issue, safety and the application of alternative testing methods for toxicity are of crucial importance as well".

Remnant oral biofilm and microorganisms after autoclaving sterilization of retrieved healing abutments.

OBJECTIVE: The purpose of this study was to evaluate the sterilization effectiveness against biofilms on retrieved healing abutments used in implant dentistry. BACKGROUND: A large number of clinicians reuse healing abutments to decrease treatment costs although it can promote infection due to the presence of remnant biofilm biomass. METHODS: One hundred and eighty-five titanium healing abutments previously used for 3 months in oral cavity were assessed in this study. Abutments were submitted to cleaning, chemical disinfection, and autoclave sterilization according to clinical guidelines. The abutments were aseptically placed into glass tubes containing specific bacterial growth medium and then incubated for 10 days. From glass tubes with bacterial growth, 100 µl medium was transferred to Schaedler's agar for morphological identification and counting of strict anaerobes and to Columbia blood agar for presumptive identification of facultative anaerobes after incubation. Isolated strains were then identified at species level by enzymatic and biochemical tests within API microorganism detection platform. Also, polymerase chain reaction (PCR) was performed for identification of undefined strains. RESULTS: After the standard cleaning and sterilization procedures, fifty-six (approximately 30%) retrieved abutments showed the presence of remnant biofilm biomass. The bacteria identified into the remnant biofilms covering the abutments were representative of the commensal oral microbiota including Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Enterococcus faecalis. CONCLUSION: Although some healing abutments did not reveal the existence of bacteria, organic components from biofilm biomass are still strongly adhered on the retentive micro-regions and surfaces of abutments and therefore that would support the accumulation of biofilm including pathogenic species leading to patients' cross-infections. Further studies should be performed on the assessment of different materials, design, and connections of the healing abutments associated with clinical disinfection procedures in implant dentistry.

Platelet activation and antimicrobial activity of L-PRF: a preliminary study.

Leukocyte and platelet rich fibrin (L-PRF) is one of the platelet concentrates used to support regeneration and healing process. Many studies showed possible immunological and antibacterial properties of L-PRF. We perform an in vitro study to analyze the effect of L-PRF on platelet activation, platelet-leukocytes interactions and antimicrobial activity, important components in the healing process. Molecular biomarkers related with platelet activation and platelet-leukocyte interactions were analyzed by means of flow cytometry when L-PRF exudate was added to whole blood platelets. L-PRF membrane was used to evaluate antimicrobial activity using Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC 90028). Our experimental design allows to evaluate platelet activation and analyze molecular biomarkers of other immune cells and platelet-leukocyte interactions. From the results obtained we can conclude that L-PRF can be a valuable tool in healing process, efficient in activating platelets of whole blood and inhibiting microbial growth. In our opinion, the use of L-PRF exudate, in addition to L-PRF membrane, presents some advantages that have to be considered in clinical trials. Additional research on the characterization and quantification of cells and its products present in the L-PRF exudate, as well as on the temporal factor released. Also, further studies using strains isolated from clinical cases are needed.

Spasmodic cough preceding CANVAS phenotype in a family with biallelic repeat expansions in RFC1.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, multisystem ataxia that remained only clinically defined, until recently, when the discovery of biallelic repeat expansion in the RFC1 gene allowed the genetic link. We describe the first Portuguese familial CANVAS harboring the pathogenic RFC1 expansion. Detail clinical features and course of four affected members are provided. Phenotype characterizations are important as the novel RFC1 mutation is expected to be a major cause of idiopathic late-onset ataxia.

Objectively measured daily-life physical activity of moderate-to-severe Brazilian asthmatic women in comparison to healthy controls: A cross-sectional study.

Considering the complex relationship between asthma symptoms and exercise, asthmatics are usually believed to be less active in daily life than healthy subjects. However, few studies have objectively assessed daily-life physical activity (DLPA) of asthmatic adults. OBJECTIVE: To objectively assess DLPA of a sample of Brazilian asthmatic women in comparison to healthy controls, and to investigate the associations between DLPA and asthma control, health-related quality of life, anxiety and depression levels, and the Six-minute walk test (6MWT) in this population. METHODS: Sixty-six women were included, 36 in the asthma group (AG) and 30 in the control group (CG). The AG was composed by clinically stable moderate-to-severe asthmatics. The CG was composed by apparently healthy volunteers. All subjects underwent DLPA assessment (considered as the average of steps taken during six consecutive days measured by a pedometer) and performed the 6MWT. Additionally, participants in the AG were assessed using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire (AQLQ), and the Hospital Anxiety and Depression Scale. RESULTS: There was no difference between the AG and the CG regarding DLPA (7490.3 ± 3330.2 vs 6876.4 ± 3242.1 steps respectively, p = 0.45), even after adjustment for covariates. DLPA was significantly correlated to the activity limitation domain of the AQLQ among asthmatics (r = 0.43, p < 0.01). CONCLUSION: Despite the association between self-perceived activity limitation and DLPA among asthmatics, there were no differences regarding DLPA between a sample of moderate-to-severe Brazilian asthmatic women and apparently healthy controls.

Effects of an unsupervised pedometer-based physical activity program on daily steps of adults with moderate to severe asthma: a randomized controlled trial.

Supervised exercise has shown benefits for subjects with asthma, but little is known about the effectiveness of unsupervised physical activity on this population. We investigated the effects of a 12-week unsupervised pedometer-based physical activity program on daily steps and on clinical and psychological parameters of adults with asthma. Clinically stable adults with moderate to severe asthma were encouraged to take daily 30-minute walks and were randomized to pedometer and control groups. The pedometer group received pedometers and individualized daily step targets. Changes in daily steps (average of steps taken during six consecutive days), six-minute walk test (6MWT), health-related quality of life, asthma control and anxiety and depression levels were assessed 12 weeks after intervention and 24-28 weeks after randomization. Thirty-seven participants were recruited and 30 completed the intervention. At 12 weeks, the groups differed significantly in daily steps (adjusted average difference, 2488 steps; 95% confidence interval [CI], 803 to 4172; p = 0.005) and in the 6MWT (adjusted average difference, 21.9 m; 95% CI, 6.6 to 37.3; p = 0.006). These differences were not significant 24-28 weeks after randomization. The program was effective in increasing daily steps of adults with moderate to severe asthma 12 weeks after intervention.

Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parameters.

We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation.

Water-mediated structuring of bone apatite.

It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization.

Exploring the molecular structure of imidazolium-silica-based nanoparticle networks by combining solid-state NMR spectroscopy and first-principles calculations.

A DFT-based molecular model for imidazolium-silica-based nanoparticle networks (INNs) is presented. The INNs were synthesized and characterized by using small-angle X-ray scattering (SAXS), NMR spectroscopy, and theoretical ab initio calculations. (11)B and (31)P HETCOR CP MAS experiments were recorded. Calculated (19)F NMR spectroscopy results, combined with the calculated anion-imidazolium (IM) distances, predicted the IM chain density in the INN, which was also confirmed from thermogravimetric analysis/mass spectrometry results. The presence of water molecules trapped between the nanoparticles is also suggested. First considerations on possible π-π stacking between the IM rings are presented. The predicted electronic properties confirm the photoluminescence emissions in the correct spectral domain.

Ivacaftor: Five-year outcomes in the West of Scotland cystic fibrosis population.

INTRODUCTION: Ivacaftor has shown to be effective in patients with cystic fibrosis (CF) with a G551D mutation. OBJECTIVES: This work aims to evaluate ivacaftor's effectiveness and safety in the real world, over 5 years, in the West of Scotland CF population. METHODS: We evaluated ivacaftor's effect on pulmonary function, body mass index (BMI), hospital bed occupancy, and adverse effects in patients ≥6 years with at least one G551D mutation. RESULTS: Statistically significant increases from baseline were observed in mean per cent predicted forced expiratory volume in 1 s (FEV1 ) at year 1 (which was maintained at years 2 and 5) and BMI over 5 years in our adolescent/adult cohort. Improvements were observed in per cent predicted FEV1 within the paediatric cohort with a suggestion of a plateau effect. The increase in paediatric BMI z-score was nonstatistically significant. There was a reduction in the number of pulmonary exacerbations requiring intravenous antibiotics and hospital bed occupancy. Ivacaftor was well tolerated. CONCLUSION: Ivacaftor was effective in our population.

Brazilian Portuguese version and content validity of the Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH).

INTRODUCTION: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) program is a personalized, progressive 12-week exercise program for people with hand problems due to rheumatoid arthritis (RA). Patients are provided with two guidance documents, the 'Patient Exercise Booklet' and the 'Personal Exercise Guide', to continue the exercises independently at home. OBJECTIVE: This study aimed to translate and culturally adapt the SARAH protocol into Brazilian Portuguese and validate its content. METHODS: The guidance documents 'Patient Exercise Booklet' and 'Personal Exercise Guide' of the SARAH program were translated and culturally adapted to Brazilian Portuguese. The content validity was obtained by calculating the content validity index (CVI). RESULTS: The Brazilian version of the SARAH protocol reached semantic, idiomatic, conceptual, and cultural equivalences. The CVI was greater than 0.8, corresponding to a satisfactory index. The verbal comprehension was 4.9, showing good verbal comprehension of the target population. CONCLUSION: The Brazilian Portuguese version of the SARAH protocol is available to Brazilian people with compromised hands due to RA with satisfactory content validity.

New perspectives in the PAW/GIPAW approach: J(P-O-Si) coupling constants, antisymmetric parts of shift tensors and NQR predictions.

In 2001, Pickard and Mauri implemented the gauge including projected augmented wave (GIPAW) protocol for first-principles calculations of NMR parameters using periodic boundary conditions (chemical shift anisotropy and electric field gradient tensors). In this paper, three potentially interesting perspectives in connection with PAW/GIPAW in solid-state NMR and pure nuclear quadrupole resonance (NQR) are presented: (i) the calculation of J coupling tensors in inorganic solids; (ii) the calculation of the antisymmetric part of chemical shift tensors and (iii) the prediction of (14)N and (35)Cl pure NQR resonances including dynamics. We believe that these topics should open new insights in the combination of GIPAW, NMR/NQR crystallography, temperature effects and dynamics. Points (i), (ii) and (iii) will be illustrated by selected examples: (i) chemical shift tensors and heteronuclear (2)J(P-O-Si) coupling constants in the case of silicophosphates and calcium phosphates [Si(5)O(PO(4))(6), SiP(2)O(7) polymorphs and α-Ca(PO(3))(2)]; (ii) antisymmetric chemical shift tensors in cyclopropene derivatives, C(3)X(4) (X = H, Cl, F) and (iii) (14)N and (35)Cl NQR predictions in the case of RDX (C(3)H(6)N(6)O(6)), ß-HMX (C(4)H(8)N(8)O(8)), α-NTO (C(2)H(2)N(4)O(3)) and AlOPCl(6). RDX, ß-HMX and α-NTO are explosive compounds.

A soft-chemistry approach to the synthesis of amorphous calcium ortho/pyrophosphate biomaterials of tunable composition.

The development of amorphous phosphate-based materials is of major interest in the field of biomaterials science, and especially for bone substitution applications. In this context, we herein report the synthesis of gel-derived hydrated amorphous calcium/sodium ortho/pyrophosphate materials at ambient temperature and in water. For the first time, such materials have been obtained in a large range of tunable orthophosphate/pyrophosphate molar ratios. Multi-scale characterization was carried out thanks to various techniques, including advanced multinuclear solid state NMR. It allowed the quantification of each ionic/molecular species leading to a general formula for these materials: [(Ca2+y Na+z H+3+x-2y-z)(PO43-)1-x(P2O74-)x](H2O)u. Beyond this formula, the analyses suggest that these amorphous solids are formed by the aggregation of colloids and that surface water and sodium could play a role in the cohesion of the whole material. Although the full comprehension of mechanisms of formation and structure is still to be investigated in detail, the straightforward synthesis of these new amorphous materials opens up many perspectives in the field of materials for bone substitution and regeneration. STATEMENT OF SIGNIFICANCE: The metastability of amorphous phosphate-based materials with various chain length often improves their (bio)chemical reactivity. However, the control of the ratio of the different phosphate entities has not been yet described especially for small ions (pyrophosphate/orthophosphate) and using soft chemistry, whereas it opens the way for the tuning of enzyme- and/or pH-driven degradation and biological properties. Our study focuses on elaboration of amorphous gel-derived hydrated calcium/sodium ortho/pyrophosphate solids at 70 °C with a large range of orthophosphate/pyrophosphate ratios. Multi-scale characterization was carried out using various techniques such as advanced multinuclear SSNMR (31P, 23Na, 1H, 43Ca). Analyses suggest that these solids are formed by colloids aggregation and that the location of mobile water and sodium could play a role in the material cohesion.

Redox-Oligomeric State of Peroxiredoxin-2 and Glyceraldehyde-3-Phosphate Dehydrogenase in Obstructive Sleep Apnea Red Blood Cells under Positive Airway Pressure Therapy.

In this study, we examined the effect of six months of positive airway pressure (PAP) therapy on Obstructive Sleep Apnea (OSA) red blood cell (RBC) proteome by two dimensional difference gel electrophoresis (2D-DIGE) - based proteomics followed by Western blotting (WB) validation. The discovered dysregulated proteins/proteoforms are associated with cell death, H2O2 catabolic/metabolic process, stress response, and protein oligomerization. Validation by nonreducing WB was performed for peroxiredoxin-2 (PRDX2) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using antibodies against the sulfinylated/sulfonylated cysteine of these proteins to better evaluate their redox-oligomeric states under OSA and/or in response to PAP therapy. The results indicated that the redox-oligomeric state of GAPDH and PRDX2 involving overoxidation by sulfinic/sulfonic acids were differentially modulated in OSA RBC, which might be compromising RBC homeostasis. PAP therapy by restoring this modulation induced a higher oligomerization of overoxidized GAPDH and PRDX2 in some patients that could be associated with eryptosis and the chaperone "gain" of function, respectively. This varied response following PAP may result from the complex interplay between OSA and OSA metabolic comorbidity. Hence, information on the redox status of PRDX2 and GAPDH in RBC will help to better recognize OSA subtypes and predict the therapeutic response in these patients. GAPDH monomer combined with body mass index (BMI) and PRDX2 S-S dimer combined with homeostatic model assessment for insulin resistance (HOMA-IR) showed to be very promising biomarkers to predict OSA and OSA severity, respectively.

Implementation of high resolution 43Ca solid state NMR spectroscopy: toward the elucidation of calcium sites in biological materials.

Calcium is one of the most abundant cations in living organisms. It is found in the mineral phase of bone and in proteins like calmodulin. However, its exact environment beyond the first coordination sphere is often unknown, thus hampering the understanding of many biological processes. Here, calcium benzoate trihydrate (Ca(C(6)H(5)COO)(2) x 3 H(2)O) was used as a model for the NMR analysis of calcium sites in biological materials, because of the similarity of its calcium coordination, to water and carboxylate ligands, to that in several calcium-proteins. First, calcium-43 magic angle spinning (MAS) and static NMR spectra of a (43)Ca enriched sample were recorded at different magnetic fields, to investigate the electronic environment of calcium. Complex static lineshapes were obtained because of the presence of anisotropic NMR interactions of similar magnitude (chemical shift anisotropy and quadrupolar interaction), and the full interpretation of the spectra required simulations and gauge-including projector augmented wave (GIPAW) DFT calculations. An NMR investigation of the coordination environment of Ca(2+) was carried out, using high resolution (13)C-(43)Ca MAS NMR experiments such as TRAPDOR (transfer of population double resonance) and heteronuclear J-spin-echoes. It was shown that despite the weakness of (13)C-(43)Ca interactions, it is possible to discriminate carbon atoms according to their calcium environment. Long-range calcium-carbon correlations were even evidenced by TRAPDOR, reaching distances >5.6 A. This work demonstrates that by combining solid state NMR experiments, DFT calculations, and simulations, it will be possible to elucidate the electronic and coordination environment of calcium in many important and complex materials.

New crystalline layered zinc phosphate with 10-membered-ring channels perpendicular to layers.

A novel layered zinc phosphate, [N(2)C(6)H(12)](2)[Zn(7)H(3)(HPO(4-x))(5)(PO(4))(3)]H(2)O, with unique 10-membered-ring ellipsoidal channels running perpendicularly to ladder-shaped tetrahedral layers, has been synthesized ionothermally via in situ generation of 1,4-diazabicyclo[2.2.2]octane.

Effects of the implementation of a hand hygiene education program among ICU professionals: an interrupted time-series analysis.

OBJECTIVE: To evaluate the effects that a hand hygiene education program has on the compliance of health professionals in an ICU. METHODS: This was a quasi-experimental study with an interrupted time-series design, conducted over a 12-month period: the 5 months preceding the implementation of a hand hygiene education program (baseline period); the 2 months of the intensive (intervention) phase of the program; and the first 5 months thereafter (post-intervention phase). Hand hygiene compliance was monitored by one of the researchers, unbeknownst to the ICU team. The primary outcome measure was the variation in the rate of hand hygiene compliance. We also evaluated the duration of mechanical ventilation (MV), as well as the incidence of ventilator-associated pneumonia (VAP) at 28 days and 60 days, together with mortality at 28 days and 60 days. RESULTS: On the basis of 959 observations, we found a significant increase in hand hygiene compliance rates-from 31.5% at baseline to 65.8% during the intervention phase and 83.8% during the post-intervention phase, corresponding to prevalence ratios of 2.09 and 2.66, respectively, in comparison with the baseline rate (p < 0.001). Despite that improvement, there were no significant changes in duration of MV, VAP incidence (at 28 or 60 days), or mortality (at 28 or 60 days). CONCLUSIONS: Our findings indicate that a hand hygiene education program can increase hand hygiene compliance among ICU professionals, although it appears to have no impact on VAP incidence, duration of MV, or mortality.

Electrooculogram and submandibular montage to distinguish different eye, eyelid, and tongue movements in electroencephalographic studies.

OBJECTIVE: We propose an electrooculogram and submandibular montage that helps to discriminate eye/eyelid/tongue movements and to differentiate them from epileptiform activity or slowing on electroencephalography (EEG). METHODS: We analyzed different eye/eyelid and tongue movements in 6 and 4 patients, respectively. Six peri-orbitally and one submandibular electrodes were placed. We referred these electrodes to an indifferent reference (Cz/Pz) and we recorded eye/eyelid and tongue movements simultaneously with the 10-20 system EEG. Additionally, we analyzed 2 seizures with the electrooculogram montage. RESULTS: The electrooculogram deflections always showed an opposite phase direction when eye/eyelid movements occurred. Conversely, epileptiform activity produced deflections in the same phase direction in all electrooculogram electrodes. The electrooculogram montage was able to distinguish eye ictal semiology. Vertical tongue movements showed opposite phase deflections between the submandibular and the inferior ocular electrodes. Horizontal tongue movements revealed opposite phase reversal deflections between both inferior ocular electrodes. CONCLUSIONS: The proposed montage accurately defines different eye/eyelid and tongue movements from brainwave activity. Additionally, it is useful to differentiate eye/eyelid movements from epileptiform activity and to characterize ictal ocular semiology, which can help localize or lateralize the epileptogenic zone. SIGNIFICANCE: We propose this new montage to provide added value to prolonged video-EEG studies.