Best Practices for Treating Blind and Visually Impaired Patients in the Emergency Department: A Scoping Review.

Introduction: Blind and visually impaired individuals, an under-represented population of the emergency department (ED), possess comorbidities and have a higher chance of in-hospital sequelae, including falls. This potentially vulnerable population, if not treated mindfully, can be subject to decreased quality of care, recurrent and/or longer hospitalizations, persistence of health issues, increased incidence of falls, and higher healthcare costs. For these reasons, it is crucial to implement holistic practices and train clinicians to treat blind and visually impaired patients in the ED setting. Methods: We identified and used a comprehensive article describing best practices for the care of blind and visually impaired patients to establish the ED-specific recommendations presented in this paper. A scoping review of the literature was then performed using PubMed to identify additional articles to support each recommendation. To ensure that recommendations could be implemented in a representative, scalable, and sustainable manner, we consulted an advocate for the blind to help refine and provide additional suggestions. Results: We identified 14 recommendations that focus on communication strategies, ED resource access, and continuity of care. The main recommendation is for the clinician to support the unique healthcare needs of the visually impaired individual and maintain the patient's autonomy. Another recommendation is the consistent use of assistive devices (eg, canes, guide dogs) to aid patients to safely ambulate in the ED. Also identified as best practices were discharge education with the use of a screen reader and timely follow-up with a primary care physician. Conclusion: While we summarize a variety of recommendations in this article, it is important to implement only the strategies that work best for the patients, personnel, and environment specific to your ED. After implementation, it is vital to refine (as frequently as needed) the interventions to optimize the strategies. This will enable the provision of exceptional and equal care to blind and visually impaired patients in the ED.

When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Metal-ring interactions in group 2 ansa-metallocenes: assessed with the local vibrational mode theory.

Ansa-metallocenes, a vital class of organometallic compounds, have attracted significant attention due to their diverse structural motifs and their pivotal roles in catalysis and materials science. We investigated 37 distinct group 2 ansa-metallocenes at the B3LYP-D3/def2-TZVP level of theory. Utilizing local mode force constants derived from our local vibrational mode theory, including a special force constant directly targeting the metal-ring interaction, we could unveil latent structural differences between solvated and non-solvated metallocenophanes and the influence of the solvent on complex stability and structure. We could quantify the intrinsic strength of the metal-cyclopentadienyl (M-Cp) bonds and the influence of the bridging motifs on the stiffness of the Cp-M-Cp angles, another determinant of complex stability. LMA was complemented by the analysis of electronic density, utilizing the quantum theory of atoms in molecules (QTAIM), which confirmed both the impact of solvent coordination on the strength of the M-Cp bond(s) and the influence of the bridging motif on the Cp-M-Cp angles. The specific effect of the ansa-motif on the M-Cp interaction was further elucidated by a comparison with linear/bent metallocene structures. In summary, our results identify the local mode analysis as an efficient tool for unraveling the intricate molecular properties of ansa-metallocenes and their unique structural features.

Iron-histidine bonding in bishistidyl hemoproteins-A local vibrational mode study.

We investigated the intrinsic strength of distal and proximal FeN bonds for both ferric and ferrous oxidation states of bishistidyl hemoproteins from bacteria, animals, human, and plants, including two cytoglobins, ten hemoglobins, two myoglobins, six neuroglobins, and six phytoglobins. As a qualified measure of bond strength, we used local vibrational force constants k a (FeN) based on local mode theory developed in our group. All calculations were performed with a hybrid QM/MM ansatz. Starting geometries were taken from available x-ray structures. k a (FeN) values were correlated with FeN bond lengths and covalent bond character. We also investigated the stiffness of the axial NFeN bond angle. Our results highlight that protein effects are sensitively reflected in k a (FeN), allowing one to compare trends in diverse protein groups. Moreover, k a (NFeN) is a perfect tool to monitor changes in the axial heme framework caused by different protein environments as well as different Fe oxidation states.

Noncovalent π Interactions in Mutated Aquomet-Myoglobin Proteins: A QM/MM and Local Vibrational Mode Study.

Protein dynamics and function is strongly connected to the energy flow taking place. Myoglobin (Mb) and its mutations are ideal systems to study the process of vibrational energy transfer (VET) at the molecular level. Anti-Stokes ultraviolet resonance Raman studies using a tryptophan (Trp) probe, introduced at different Mb positions by amino acid replacement, have suggested that the amount of VET depends on the position of the Trp probe relative to the heme group. Inspired by this experimental work, we explored the strength of noncovalent π interactions, as well as covalent interactions for both the axial and distal ligands bound to iron in aquomet-Mb with the local vibrational mode analysis (LMA), originally developed by Konkoli and Cremer. Two sets of noncovalent interactions were investigated: (1) the interaction between the water ligand and Trp rings and (2) the interaction between the Trp and the porphyrin rings of the heme group. We assessed the strength of these noncovalent interactions via a special local mode force constant. Various Trp-modified water-bound ferric Mb proteins in the ground state were studied (6 in total) using gas-phase and QM/MM calculations followed by LMA. Our results disclose that VET is indeed dependent on the position of the Trp probe relative to the heme group but also on the tautomeric nature of distal histidine. They provide new guidelines on how to assess noncovalent π interactions in proteins utilizing LMA and how to use these data to explore VET, and more generally protein dynamics and function.

Reaction mechanism - explored with the unified reaction valley approach.

One of the ultimate goals of chemistry is to understand and manipulate chemical reactions, which implies the ability to monitor the reaction and its underlying mechanism at an atomic scale. In this article, we introduce the Unified Reaction Valley Approach (URVA) as a tool for elucidating reaction mechanisms, complementing existing computational procedures. URVA combines the concept of the potential energy surface with vibrational spectroscopy and describes a chemical reaction via the reaction path and the surrounding reaction valley traced out by the reacting species on the potential energy surface on their way from the entrance to the exit channel, where the products are located. The key feature of URVA is the focus on the curving of the reaction path. Moving along the reaction path, any electronic structure change of the reacting species is registered by a change in the normal vibrational modes spanning the reaction valley and their coupling with the path, which recovers the curvature of the reaction path. This leads to a unique curvature profile for each chemical reaction, with curvature minima reflecting minimal change and curvature maxima indicating the location of important chemical events such as bond breaking/formation, charge polarization and transfer, rehybridization, etc. A decomposition of the path curvature into internal coordinate components or other coordinates of relevance for the reaction under consideration, provides comprehensive insight into the origin of the chemical changes taking place. After giving an overview of current experimental and computational efforts to gain insight into the mechanism of a chemical reaction and presenting the theoretical background of URVA, we illustrate how URVA works for three diverse processes, (i) [1,3] hydrogen transfer reactions; (ii) α-keto-amino inhibitor for SARS-CoV-2 Mpro; (iii) Rh-catalyzed cyanation. We hope that this article will inspire our computational colleagues to add URVA to their repertoire and will serve as an incubator for new reaction mechanisms to be studied in collaboration with our experimental experts in the field.

Effect of build orientation in gloss, roughness and color of 3D-printed resins for provisional indirect restorations.

OBJECTIVES: The purpose of this study was to evaluate the effect of build orientation of 3D-printed provisional resins (3DRs) on gloss (Gs), surface roughness (Sa), maximum profile valley depth (Rv), and color difference (∆E00). METHODS: PMMA CAD/CAM blocks (Vita Temp/Vita) were sectioned and served as a Control. Four 3DRs (Cosmos-SLA/Yller, Cosmos-DLP/Yller, PriZma-Bioprov/Makertech, Nanolab/Wilcos) were obtained as discs (15-mm diameter, 2.5-mm thickness) in three orientations (0°, 45°, and 90°) using different 3D printers (Form 2/Formlabs, P30/Straumann, Hunter/Flashforge, W3D/Wilcos, respectively). Samples were then cleaned with isopropyl alcohol prior to post-curing in specific post-curing units. Half of the samples' surface was covered with an adhesive tape and submitted to 10,000 toothbrushing (TB) cycles. The Gs and Sa at the brushed and not brushed surfaces were evaluated with a glossmeter (Novo-curve) and a laser confocal microscope (OLS5000) (n = 10), which also obtained the Rv and 3D representative images of the interface between not brushed and brushed surfaces. Electron microscopy images of the surface of some samples was also performed (n = 3). On another set of samples (n = 5), the coordinates of luminosity and color were obtained with a spectrophotometer (Easyshade V) at baseline and after 16.7 h and 200 h of UVB aging, to calculate the ∆E00 using CIEDE:2000 formula. Additionally, 3DRs photoinitiators were identified using a minispectrometer (USB2000 +) (n = 5). Data of Gs and Sa were submitted to three-way-, Rv to two-way-, and ∆E00 to mixed-ANOVA tests, followed by Tukey's test (α = 0.05). For all variables, results from experimental groups were compared to control using Dunnett's test (α = 0.05). Student's t-test was used to compare the control at different TB cycles (Gs, Sa) or aging periods (∆E00) (α = 0.05). RESULTS: Build orientation of 3DRs did not influence any of the variables studied. The 10,000 TB cycles resulted in a decrease in Gs and increase in Sa for all resins tested. The control showed higher Gs after 10,000 TB cycles than Cosmos-SLA and Nanolab resins. Compared to all 3DRs, Control presented lower ∆E00 after 200 h of UVB aging. All 3DRs presented higher ∆E00 than the clinically acceptable after 200 h of UVB aging. Lucirin® TPO was identified in all 3DRs, although PriZma might also present other photoinitiators and Nanolab might present Irgacure 369. SIGNIFICANCE: Alterations in build orientation are very useful and frequently performed in the day-today of 3D-printing, thus its effect in the optical properties and in the topography of 3D-printed restorations is very relevant. For the evaluated 3D-printed provisional resins, build orientation did not influence any of the variables studied (Gs, Sa, Rv, and ∆E00), even after toothbrushing cycles and UVB aging.

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages.

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.

A Feshbach resonance in collisions between triplet ground-state molecules.

Collisional resonances are important tools that have been used to modify interactions in ultracold gases, for realizing previously unknown Hamiltonians in quantum simulations1, for creating molecules from atomic gases2 and for controlling chemical reactions. So far, such resonances have been observed for atom-atom collisions, atom-molecule collisions3-7 and collisions between Feshbach molecules, which are very weakly bound8-10. Whether such resonances exist for ultracold ground-state molecules has been debated owing to the possibly high density of states and/or rapid decay of the resonant complex11-15. Here we report a very pronounced and narrow (25 mG) Feshbach resonance in collisions between two triplet ground-state NaLi molecules. This molecular Feshbach resonance has two special characteristics. First, the collisional loss rate is enhanced by more than two orders of magnitude above the background loss rate, which is saturated at the p-wave universal value, owing to strong chemical reactivity. Second, the resonance is located at a magnetic field where two open channels become nearly degenerate. This implies that the intermediate complex predominantly decays to the second open channel. We describe the resonant loss feature using a model with coupled modes that is analogous to a Fabry-Pérot cavity. Our observations provide strong evidence for the existence of long-lived coherent intermediate complexes even in systems without reaction barriers and open up the possibility of coherent control of chemical reactions.

Oral conditions associated with oral health related quality of life: A population-based cross-sectional study in Brazil.

AIM: To investigate the association between 11 oral conditions and oral health related quality of life (OHRQoL). MATERIALS AND METHODS: This cross-sectional study used a multistage sampling strategy to draw a representative sample of adults aged ≥35 years living in Porto Alegre, Brazil. OHRQoL was assessed using OHIP-14. Oral examinations were conducted to assess gingivitis, dental calculus, tooth loss, gingival recession (GR), dentine hypersensitivity (DHS), dental caries (DFT), dental erosion, and non-carious cervical lesions (NCCL). Questionnaires recorded the following self-reported oral variables: xerostomia, halitosis, and perceived need for dental treatment. Structural Equation Models were used to assess the associations adjusting to demographic and behavioral variables. RESULTS: 1022 individuals were analyzed. The overall OHIP mean equaled 9.2 ± 9.7 points. Xerostomia [coefficient (coef)=0.10], halitosis (coef=0.28), DFT (coef=0.16), and DHS (coef=0.19) were significantly and directly associated with negative impacts of OHIP-14. GR was significantly and indirectly associated with poor OHRQoL due to higher DHS. Perceived need for dental treatment was significantly and directly associated with higher OHIP-14 (coef=0,40). CONCLUSIONS: Poor OHRQoL was observed in a sample of Brazilian adults and old people. Five important oral conditions were associated to poor OHRQoL. Tooth loss, gingivitis, calculus, dental erosion and NCCL did not associate with OHRQoL. CLINICAL SIGNIFICANCE: Poorer oral health related quality of life is observed in a Brazilian urban area compared to other parts of the world. Xerostomia, halitosis, dental caries, gingival recession, and dentine hypersensitivity may be targeted to improve oral health and consequently oral health related quality of life.

MR Imaging of Epithelial Ovarian Neoplasms Part I: Benign and Borderline.

Benign and borderline epithelial ovarian tumors represent a substantial proportion of incidental adnexal lesions and familiarity with the typical imaging features on MR imaging can aid in their diagnosis and management. Clinical information such as menstrual status, age, and associated conditions is also important considerations when evaluating an adnexal lesion. Radiologists play an integral role in the preoperative evaluation process and can help guide treatment, particularly in those with lesions demonstrating benign or borderline features and those who may be candidates for fertility-sparing surgery.

Automatic Generation of Local Vibrational Mode Parameters: From Small to Large Molecules and QM/MM Systems.

LModeAGen, a new protocol for the automatic determination of a nonredundant, complete set of local vibrational modes is reported, which is based on chemical graph concepts. Whereas local mode properties can be calculated for a selection of parameters targeting specific local modes of interest, a complete set of nonredundant local mode parameters is requested for the adiabatic connection scheme (ACS), relating each local vibrational mode with a normal mode counterpart, and for the decomposition of normal modes (CNM) in terms of local mode contributions, a unique way to analyze vibrational spectra. So far, nonredundant parameter sets have been generated manually following chemical intuition or from a set of redundant parameters in a trial-and-error fashion, which has hampered the study of larger systems with hundreds of parameters. LModeAGen was successfully applied for a test set of 11 systems, ranging from small molecules to the large QM (>100 atoms) subsystem of carbomonoxy-neuroglobin protein, described with a hybrid QM/MM method. The ωB97X-D/aug-cc-pVDZ, M06L/def2-TZVP, and QM/MM ωB97X-D/6-31G(d,p)/AMBER model chemistries were adopted for the description of the molecules in the test set. Our new protocol is an important step forward for a routine ACS and CNM analysis of the vibrational spectra of complex and large systems with hundreds of atoms, providing new access to important encoded electronic structure information.

The Local Vibrational Mode Theory and Its Place in the Vibrational Spectroscopy Arena.

This Feature Article starts highlighting some recent experimental and theoretical advances in the field of IR and Raman spectroscopy, giving a taste of the breadth and dynamics of this striving field. The local mode theory is then reviewed, showing how local vibrational modes are derived from fundamental normal modes. New features are introduced that add to current theoretical efforts: (i) a unique measure of bond strength based on local mode force constants ranging from bonding in single molecules in different environments to bonding in periodic systems and crystals and (ii) a new way to interpret vibrational spectra by pinpointing and probing interactions between particular bond stretching contributions to the normal modes. All of this represents a means to work around the very nature of normal modes, namely that the vibrational motions in polyatomic molecules are delocalized. Three current focus points of the local mode analysis are reported, demonstrating how the local mode analysis extracts important information hidden in vibrational spectroscopy data supporting current experiments: (i) metal-ligand bonding in heme proteins, such as myoglobin and neuroglobin; (ii) disentanglement of DNA normal modes; and (iii) hydrogen bonding in water clusters and ice. Finally, the use of the local mode analysis by other research groups is summarized. Our vision is that in the future local mode analysis will be routinely applied by the community and that this Feature Article serves as an incubator for future collaborations between experiment and theory.

Laser irradiation prevents root caries: Microhardness and scanning electron microscopy analysis.

Context: A promising option for the prevention of dental caries is the use of laser irradiation. Aims: Evaluate the effects of Er:YAG, Nd:YAG, and CO2 laser irradiation, associated or not to 2% sodium fluoride (2% NaF), on root caries prevention. Material and Methods: One hundred and four human root dentin samples were divided in eight groups (n = 13). A 9-mm2-area on each dentin sample was delimited and treated as follows: G1: no treatment (control); G2: 2% NaF; G3: Er:YAG; G4: 2% NaF + Er:YAG; G5: Nd:YAG; G6: 2% NaF + Nd:YAG; G7: CO2; G8: 2% NaF + CO2. When used, the 2% NaF was applied before irradiation for 4 min. The samples were subjected to a 2-week cariogenic challenge, consisted of daily immersion in de-remineralizing solutions for 6 h and 18 h, respectively. Knoop hardness (KHN) were evaluated (10 g and 20 s) at different depths from the dentin surface. The samples (n = 3) were prepared for scanning electron microscopy (SEM). Microhardness data were analysed by one-way analysis of variance (ANOVA) and Fisher's test (α = 5%). Results: The Er:YAG laser group (KHN = 41.30) promoted an increase in acid resistance of the dentin (P < 0.05) when compared to all groups. There was no synergism between laser irradiation and 2% NaF application. Morphological changes were observed after irradiation with all lasers; carbonization and cracks were also observed, except when Er:YAG were used. Conclusions: Er:YAG laser irradiation can safely increase the acid resistance of the dentin surface of the root, since it promoted a significant increase in surface hardness. The application of 2% NaF did not result in a synergistic effect.

Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer.

BACKGROUND: There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P450 2D6 (CYP2D6) polymor-phisms. AIM: To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes. METHODS: Eighty-two women were recruited. Seventy-eight completed CYP2D6 genotyping and were categorized into poor, intermediate (IM) and extensive or ultra metabolizer phenotypes. Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent. RESULTS: More than 70% of the women had an IM phenotype, 32% an extensive or ultra metabolizer phenotype, and 0% had a poor metabolizer phenotype. Regardless of genotype, more women opted for aromatase inhibitors. Overall, 80% of women completed 5 years of hormonal therapy. Five women developed recurrence, 3 contralateral breast cancer, 5 died, and 1 was diagnosed with a second primary cancer. Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype, though not statistically significant [P = 0.743, hazard ratio (HR): 1.441, 95% confidence interval (CI): 0.191 to 10.17 and P = 0.798, HR: 1.327, 95%CI: 0.172 to 9.915, respectively]. Women receiving aromatase inhibitors also appeared to have a better, but also nonsignificant, 5-year recurrence-free and overall survival (P = 0.253, HR: 0.368, 95%CI: 0.031 to 0.258 and P = 0.292, HR: 0.252, 95%CI: 0.005 to 4.951, respectively). CONCLUSION: The IM phenotype was highly prevalent but was not associated with clinical outcome.

Phosphoric acid containing proanthocyanidin enhances bond stability of resin/dentin interface.

Proanthocyanidin (PA) is a promising dentin biomodifier due to its ability to stabilize collagen fibrils against degradation by matrix metalloproteinases (MMPs); however, the most effective protocol to incorporate PA into bonding procedures is still unclear. This study evaluated the effect of dentin biomodification with a PA acid etchant on MMP activity, adhesive interface morphology and resin-dentin microtensile bond strength. Sound extracted human molars were flattened to expose dentin and acid-etched for 15 s according to the groups: EXP - experimental phosphoric acid; EXP+PA - experimental phosphoric acid 10% PA; TE - total-etching system; SE - self-etching system. Samples were restored with composite resin and stored in distilled water (37ºC). MMP activity and interface morphology were analyzed after 24 h by in situ zymography (n=6) and scanning electron microscopy (n=3), respectively. The resin-dentin microtensile bond strength (µTBS) was evaluated after 24 h and 6 months storage (n=6). Significantly higher MMP activity was detected in etched dentin compared with untreated dentin (p<0.05), but no difference among acid groups was found. Resin tags and microtags, indicative of proper adhesive system penetration in dentinal tubules and microtubules, were observed along the hybrid layer in all groups. There was no difference in µTBS between 24 h and 6 months for EXP+PA; moreover, it showed higher long-term µTBS compared with TE and EXP (p<0.05). The results suggest that 15 s of biomodification was not sufficient to significantly reduce MMP activity; nonetheless, EXP+PA was still able to improve resin-dentin bond stability compared with total- and self-etching commercial systems.

Phosphoric acid containing proanthocyanidin enhances bond stability of resin/dentin interface

Abstract Proanthocyanidin (PA) is a promising dentin biomodifier due to its ability to stabilize collagen fibrils against degradation by matrix metalloproteinases (MMPs); however, the most effective protocol to incorporate PA into bonding procedures is still unclear. This study evaluated the effect of dentin biomodification with a PA acid etchant on MMP activity, adhesive interface morphology and resin-dentin microtensile bond strength. Sound extracted human molars were flattened to expose dentin and acid-etched for 15 s according to the groups: EXP - experimental phosphoric acid; EXP+PA - experimental phosphoric acid 10% PA; TE - total-etching system; SE - self-etching system. Samples were restored with composite resin and stored in distilled water (37ºC). MMP activity and interface morphology were analyzed after 24 h by in situ zymography (n=6) and scanning electron microscopy (n=3), respectively. The resin-dentin microtensile bond strength (μTBS) was evaluated after 24 h and 6 months storage (n=6). Significantly higher MMP activity was detected in etched dentin compared with untreated dentin (p<0.05), but no difference among acid groups was found. Resin tags and microtags, indicative of proper adhesive system penetration in dentinal tubules and microtubules, were observed along the hybrid layer in all groups. There was no difference in μTBS between 24 h and 6 months for EXP+PA; moreover, it showed higher long-term μTBS compared with TE and EXP (p<0.05). The results suggest that 15 s of biomodification was not sufficient to significantly reduce MMP activity; nonetheless, EXP+PA was still able to improve resin-dentin bond stability compared with total- and self-etching commercial systems.

Resumo A proantocianidina (PA) é um biomodificador dentinário promissor devido a sua capacidade de estabilizar as fibrilas colágenas contra a degradação por metaloproteinases da matriz (MMPs); no entanto, o protocolo mais eficaz para a incorporação de PA em procedimentos adesivos ainda não está claro. Este estudo avaliou o efeito da biomodificação da dentina com um condicionador ácido contendo PA na atividade de MMPs, morfologia da interface adesiva e resistência à microtração resina-dentina. Molares humanos extraídos foram lixados para exposição da dentina e condicionados com ácido por 15 s de acordo com os grupos: EXP - ácido fosfórico experimental; EXP+PA - ácido fosfórico experimental com 10% PA; TE - sistema total-etch; SE - sistema self-etch. As amostras foram restauradas com resina composta e armazenadas em água destilada (37ºC). A atividade de MMP e morfologia da interface foram analisadas após 24 h por zimografia in situ (n=6) e microscopia eletrônica de varredura (n=3), respectivamente. A resistência à microtração resina-dentina (μTBS) foi avaliada após 24 horas e 6 meses de armazenamento (n=6). Atividade de MMP detectada na dentina condicionada foi significativamente maior em comparação com a dentina não tratada (p <0,05), mas não houve diferenças entre os diferentes ácidos. Tags e microtags de resina, indicativos de uma penetração adequada do sistema adesivo nos túbulos e microtúbulos dentinários, foram observadas ao longo da camada híbrida em todos os grupos. Não houve diferença entre os valores de μTBS de 24 h e 6 meses para EXP+PA; além disso, EXP+PA apresentou maiores valores de μTBS após 6 meses em comparação com TE e EXP (p <0,05). Os resultados sugerem que a biomodificação por 15 s não foi suficiente para reduzir significativamente a atividade de MMP; apesar disso, EXP + PA foi capaz de melhorar a estabilidade da interface resina-dentina em comparação com sistemas total- e self-etch comerciais.

Systematic review of interruptions in the emergency department work environment.

OBJECTIVE: The purpose of this systematic review is to describe the operationalization of interruptions measurement and to synthesize the evidence on the causes and consequences of interruptions in the emergency department (ED) work environment. METHODS: This systematic review of studies explores the causes and consequences of interruptions in the ED. Of 2836 abstract/titles screened, 137 full-text articles were reviewed, and 44 articles met inclusion criteria of measuring ED interruptions. RESULTS: All articles reported primary data collection, and most were cohort studies (n = 30, 68%). Conceptual or operational definitions of interruptions were included in 27 articles. Direct observation was the most common approach. In half of the studies, quantitative measures of interruptions in the ED were descriptive only, without measurements of interruptions' consequences. Twenty-two studies evaluated consequences, including workload, delays, satisfaction, and errors. Overall, relationships between ED interruptions and their causes and consequences are primarily derived from direct observation within large academic hospitals using heterogeneous definitions. Collective strengths of interruptions research in the ED include structured methods of naturalistic observation and definitions of interruptions derived from concept analysis. Limitations are conflicting and complex evaluations of consequences attributed to interruptions, including the predominance of descriptive reports characterizing interruptions without direct measurements of consequences. CONCLUSIONS: The use of standardized definitions and measurements in interruptions research could contribute to measuring the impact and influence of interruptions on clinicians' productivity and efficiency as well as patients' outcomes, and thus provide a basis for intervention research.

Efficient drug development of oseltamivir capsules based on process control, bioequivalence and PBPK modeling.

Oseltamivir phosphate is used to treat influenza. For registration of a generic product, bioequivalence studies are crucial, however, in vitro studies can sometimes replace the conventional human pharmacokinetic. To assess whether the dissolution profile is comparable with the in vivo release, physiologically based pharmacokinetic absorption models (PBPK) are being used. The aim of the study was to develop a generic capsule of oseltamivir phosphate 30 mg with process understanding and control, development of PBPK model and comparison of virtual bioequivalence study (VBE) to the real bioequivalence study that was also performed. For that, 30 mg capsules were prepared by wet granulation according to 22 full factorial design. The biobatch was prepared with the selected process and a batch was made with the API from the second manufacture. Both manufactures presented polymorph A and the second manufacture showed higher particle size. Product batches produced without adding water during granulation showed higher dissolution. The addition of water associated with higher conical mill speed, lowered the average weight of the capsules. The biobatch dissolution was similar to Tamiflu; also, they were bioequivalent. The crossover VBE between the biobatch and Tamiflu corroborated with the real bioequivalence study. The same result was found for the batch with higher particle size. PBPK model showed that computer simulations can help pharmaceutical companies to replace in vivo studies.