Prevalence of orofacial pain in individuals with mild cognitive impairment or dementia: A systematic review and meta-analysis.

BACKGROUND: This systematic review investigated the prevalence of orofacial pain in patients with mild cognitive impairment (MCI) or dementia. MATERIALS AND METHODS: The search was conducted in five databases (Medline (Ovid), Embase (Ovid), CINAHL, Scopus and LILACS), in three grey literature sources and in included articles' reference lists. Three independent reviewers performed study selection, quality appraisal and data extraction. The risk of bias was assessed with the National Institutes of Health tool. Prevalence was calculated using the random-effects model. Subgroup analysis and meta-regression were used to explore the heterogeneity of results. RESULTS: The database and grey literature search led to 12 246 results, from which nine studies were included; a further four were selected through citation searching. The total sample comprised 6115 patients with dementia and 84 with MCI. All studies had high risk of bias. The overall estimated pooled prevalence of orofacial pain among dementia participants was 19.0% (95% CI, 11.0%-27.0%; I2 , 97.1%, P < .001). Only one study included MCI participants, among which the prevalence of orofacial pain was 20.5%. Subgroup analysis demonstrated that the different sources of diagnosis might explain the heterogeneity. A higher prevalence of orofacial pain was observed in dementia participants aged over 80 years or living in nursing homes. Meta-regression analysis showed a nonlinear relationship between age and the prevalence of orofacial pain. CONCLUSIONS: The pooled data from the primary studies revealed that 2 out of 10 patients with dementia have orofacial pain. Further research is needed to clarify the magnitude in individuals with MCI.

Perceção dos enfermeiros das competências de tomada de decisão na triagem de Manchester / Nurses' perceptions of decision-making skills in the Manchester Triage System / Percepción de los enfermeros de las habilidades de toma de decisiones en triaje de Manchester

Resumo Enquadramento: A triagem de prioridades caracteriza-se por um complexo processo de tomada de decisão que visa avaliar a gravidade clínica. Objetivo: Analisar relações entre as características socioprofissionais dos enfermeiros de um serviço de urgência e a perceção das competências de tomada de decisão na triagem. Metodologia: Estudo descritivo-correlacional e transversal. A amostra foi de 47 enfermeiros e para a recolha de dados recorreu-se ao Triage Decision Making Inventory, versão portuguesa. Resultados: Na perceção das competências de tomada de decisão, as características cognitivas/confiança na habilidade obtiveram a média mais elevada (4,94 ± 0,420) e a Intuição a média mais baixa (4,44 ± 0,697). Observaram-se correlações significativas entre as características cognitivas/confiança na habilidade, intuição, pensamento crítico do triador e o tempo de experiência no serviço de urgência, bem como, entre a idade do triador, a experiência profissional e as características cognitivas/confiança na habilidade. Conclusão: A tomada de decisão na triagem é influenciada positivamente pela experiência no serviço de urgência, sendo as características cognitivas/confiança na habilidade as competências mais valorizadas pelos enfermeiros.

Abstract Background: Priority triage is a complex decision-making process used to assess clinical severity. Objective: This study aims to explore the association between the socio-professional characteristics of emergency department nurses and their perceptions of decision-making skills during triage. Methodology: A cross-sectional descriptive-correlational study was conducted with a sample of 47 nurses. The Portuguese version of the Triage Decision-Making Inventory (TDMI) was used for data collection. Results: Regarding nurses' perceptions of their decision-making skills, the highest mean score (4.94 ± 0.420) was found in cognitive characteristics/Skill confidence and the lowest mean score in Intuition (4.44 ± 0.697). Significant correlations were found between cognitive characteristics/skill confidence, intuition, and critical thinking and the length of experience in emergency departments, as well as between cognitive characteristics/Skill confidence and the triage nurses' age and professional experience. Conclusion: Experience in the emergency department has a positive impact on triage decision-making skills. Nurses place the highest value on cognitive characteristics/skill confidence.

Resumen Marco contextual: El triaje de prioridades se caracteriza por un complejo proceso de toma de decisiones dirigido a evaluar la gravedad clínica. Objetivo: Analizar la relación entre las características socioprofesionales del personal de enfermería de un servicio de urgencias y su percepción de las competencias para la toma de decisiones en el triaje. Metodología: Estudio descriptivo-correlacional de corte transversal. La muestra estuvo constituida por 47 enfermeros y los datos se recogieron mediante el Triage Decision-Making Inventory, versión portuguesa. Resultados: En la percepción de las competencias para la toma de decisiones, las características cognitivas/confianza en la habilidad tuvieron la media más alta (4,94 ± 0,420) y la Intuición tuvo la media más baja (4,44 ± 0,697). Se observaron correlaciones significativas entre las características cognitivas/confianza en la habilidad, la Intuición y el pensamiento crítico del enfermero de triaje, y la antigüedad en el servicio de urgencias, así como entre la edad del enfermero de triaje, la experiencia profesional y las características cognitivas/confianza en la habilidad. Conclusión: La toma de decisiones en el triaje está positivamente influenciada por la experiencia en urgencias, y las características cognitivas/confianza en la habilidad son las competencias más valoradas por los enfermeros.

The invasive Egeria densa macrophyte and its potential as a new renewable energy source: A study of degradation kinetics and thermodynamic parameters.

The increase in global demand, along with environmental concerns, has led to the need for new sources that can supply the energy needed for socioeconomic development while reducing pollutant emissions. Aquatic biomasses, especially those of invasive aquatic macrophytes, can be potential energy sources, and this study evaluated the thermal degradation of the invasive Egeria densa macrophytes (EDM) in an inert environment at four heating rates to evaluate its potential as a low-cost biomass and bioenergy source. Pyrolysis experiments were performed using a thermogravimetric analyzer. The thermal profile of invasive EDM has three main events (multiple stages). Stages (i) and (ii) occur at a temperature range of 125-395 °C and represent the decomposition of carbohydrates such as hemicellulose and cellulose. Stage (iii) occurs between 395 and 500 °C and mainly relates to the decomposition of lignin. Thermal data have been used to analyze kinetic parameters through isoconversional methods, and the activation energy (Ea) value of EDM showed variation at different conversion points. The highest Ea values were observed for conversion rates of 0.3-0.6 due to the increased energy required to break down the lignocellulosic chains during decomposition. The small difference between the enthalpy change and Ea values for the different isoconversional methods can be due to a small potential energy barrier, which reflects the feasibility that the reaction can occur under the expected conditions. Gibbs free energy (137-145 kJ mol-1) and high heating value (13.40 MJ/kg) revealed a significant bioenergy potential for EDM biomass.

Online search interest in the use of antibiotics for dental pain: an infodemiology study / Interesse em pesquisas online sobre o uso de antibióticos para dor dentária: um estudo infodemiológico

Objective: The objective of this study was to evaluate the online search interest pertaining to queries regarding antibiotics for dental pain. Material and Methods : Google Trends™ was used to identify the online search interest. Previously, a literature search was performed on the most frequently used antibiotics in dentistry in Brazil. Accordingly, the search terms used were Amoxicillin (AM), Clindamycin (CD), Azithromycin (AZ) and Metronidazole (MD), with the phrase "for toothache" in Portuguese and English. A time-series covered the last 240 weeks (from 2015 to 2020), and the results of each term were compared to their respective annual value. Geographic regions were also evaluated. To obtain a relative search volume (RSV), the resulting Google Trends™ numbers were then scaled to a range from 0 to 100 based on the ratio of searches on a topic to searches across all topics. Results : We observed an upward trend in all antibiotics search terms over the 5 years analyzed, with a peak of greater interest in 2019. The antibiotic of most interest related to toothache was 'AM', followed by 'AZ', 'MD', and 'CD'. The annual RSV of toothache searches rose steadily from 2015 to 2020. Variations were observed between Brazilian geographic regions, and the Northeast region presented with the greatest interest in the topic. Conclusion : Although there were variations in annual and regional trends, an expressive and persistent increase in collective interest regarding the use of antibiotics related to toothache, mainly amoxicillin, was observed. Our findings provide insights for public health promotion programs. (AU)

Objetivo: O objetivo deste estudo foi avaliar o interesse da pesquisa online em consultas sobre antibióticos para dor de dente. Material e métodos : o Google Trends™ foi usado para identificar o interesse de pesquisa online. Anteriormente, foi realizada uma pesquisa bibliográfica sobre os antibióticos mais utilizados em odontologia no Brasil. A partir daí, os termos de busca utilizados foram Amoxicilina (AM), Clindamicina (CD), Azitromicina (AZ) e Metronidazol (MD) com os termos "para dor de dente" em português e inglês. Uma série histórica abrangeu as últimas 240 semanas (abril de 2015 a abril de 2020), e os resultados de cada período foram comparados com seus respectivos valores anuais. Regiões geográficas também foram avaliadas. Os números resultantes do Google Trends ™ são dimensionados para um intervalo de 0 a 100 com base na proporção de um tópico para todas as pesquisas em todos os tópicos de busca. Isso é chamado de volume relativo de pesquisa (RSV). Resultados : Foi observada uma tendência crescente para todos os termos de antibióticos ao longo dos 5 anos analisados, com um pico de maior interesse em 2019. O antibiótico de maior interesse na dor de dente foi 'AM', seguido por 'AZ', 'MD' e 'CD'. O RSV anual das buscas de dor de dente cresceu continuamente de 2015 a 2020. Variações foram observadas entre as regiões geográficas brasileiras, sendo que a Região Nordeste apresentou o maior interesse pelo tema. Conclusão : Embora tenha havido variação nas tendências anuais e regionais, observou-se um aumento expressivo e persistente do interesse coletivo pelo uso de antibióticos relacionados à dor de dente, principalmente a amoxicilina. Nossas descobertas fornecem insights para programas de promoção pública.(AU)

Triagem de manchester: processos de decisão dos enfermeiros num Hospital do Norte de Portugal / Manchester Triage: decision processes of nurses in a hospital in Northern Portugal

O Serviço de Urgência, pelas suas particularidades, apresenta elevada afluência de doentes com diferentes critérios de gravidade. Torna-se, portanto, crucial priorizar o atendimento mediante a gravidade da situação clínica, com recurso a sistemas de triagem validados. Em Portugal, foi adotado o sistema de triagem de Manchester, onde o enfermeiro assume particular relevância. A tomada de decisão do enfermeiro na triagem é fundamental para a rapidez, segurança e qualidade da assistência em saúde. O estudo teve como objetivos: conhecer as características dos processos de triagem num serviço de urgência da região norte de Portugal, no ano 2019; conhecer os fatores associados à perceção dos enfermeiros triadores sobre as habilidades de tomada de decisão na triagem. Trata-se de um estudo descritivo-correlacional, transversal e retrospetivo, com uma amostra de 68381 registos do SClínico®, relativos às triagens realizadas entre 01 de janeiro de 2019 e 31 de dezembro de 2019 e de 47 enfermeiros triadores, aos quais, para recolha de dados, se aplicou um questionário sociodemográfico e profissional e a versão portuguesa de Marques (2014) do Triage Decision Making Eventory (TDMI). Dos registos de triagem, predomina o sexo feminino (54,7%) e idades entre os 18 e 102 anos, com média de 57,31±20,866 anos. A maioria das admissões têm proveniência do domicílio (66,9%). O maior fluxo é registado nos turnos da manhã (56,8%), às segundasfeiras (17,1%) e no mês de agosto (9,8%). O fluxograma mais frequente é problemas nos membros (18,5%), o discriminador dor moderada (31,3%) e a prioridade urgente (57,7%). A média de tempos é de: 29,26±83,720 minutos de demora para triagem; 2,08±1,204 minutos de duração da triagem; 17,62±16,137 minutos de demora para a primeira observação médica; 333,70±478,789 minutos de permanência no serviço de urgência. A maioria tem alta para o domicílio (41,2%). Relativamente aos enfermeiros triadores, são maioritariamente do sexo feminino (74,5%). As idades variam entre os 27 e os 63 anos, com média de 41,02±9,389 anos. Predominam os licenciados (85,1%) e a categoria de enfermeiro (63,8%). A maioria dos enfermeiros detém experiência profissional superior a 5 anos, na profissão (89,4%) e no serviço de urgência (74,5%). Relativamente à triagem de Manchester, a maioria realizou formação entre 3 e 5 anos (44,7%) e realizam triagem com uma frequência de 6 a 10 vezes por mês (48,9%). Os enfermeiros têm uma perceção positiva sobre as suas habilidades na tomada de decisão na triagem, com médias mais elevadas na habilidade Características Cognitivas/Confiança na Habilidade (4,94±0,420) e as mais baixas na Intuição (4,44±0,697). Observamos correlações significativas entre o TDMI, as habilidades Características Cognitivas/Confiança na Habilidade, Intuição, Pensamento Crítico do triador e a experiência profissional no serviço de urgência, bem como entre a idade do triador, a experiência na profissão e as habilidades características cognitivas e confiança. Em síntese, as habilidades de tomada de decisão na triagem são influenciadas positivamente pela experiência profissional em contexto de urgência, sendo as habilidades Características Cognitivas/Confiança na Habilidade as mais valorizadas pelos enfermeiros triadores.

The Emergency Department, due to its particularities, has a high inflow of patients with different severity criteria. Therefore, it is crucial to prioritize care according to the severity of the clinical situation, using validated triage systems. In Portugal, the Manchester triage system was adopted, where nurses are particularly important. The nurse's decisionmaking in triage is essential for the speed, safety, and quality of health care. This study aimed to identify the characteristics of the triage processes in an emergency department in the northern region of Portugal, in 2019, and identify the factors associated with the triage nurses' perception of their decision-making skills in triage. This is a descriptive-correlational, cross-sectional and retrospective study, with a sample of 68381 SClínico® records, related to triage performed between January 1, 2019 and December 31, 2019, and 47 triage nurses, who received a sociodemographic and professional questionnaire and Marques' (2014) Portuguese version of the Triage Decision Making Inventory (TDMI). Of the triage records, there is a predominance of female patients (54.7%) and ages between 18 and 102 years, with a mean of 57.31±20.866 years. Most admissions come from home (66.9%). The highest flow is recorded in the morning shifts (56.8%), on Mondays (17.1%) and in the month of August (9.8%). The most frequent flowchart is limb problems (18.5%), the discriminator moderate pain (31.3%) and the priority urgent (57.7%). The average times are: 29.26±83.720 minutes of delay to triage; 2.08±1.204 minutes of triage duration; 17.62±16.137 minutes of delay to first medical observation; 333.70±478.789 minutes of stay in the emergency department. Most are discharged home (41.2%). Regarding triage nurses, they are mostly female (74.5%). Their ages range from 27 to 63 years, with a mean of 41.02 ± 9.389 years. Graduates (85.1%) and nurses (63.8%) predominated. Most nurses had more than 5 years of professional experience in the profession (89.4%) and in the emergency department (74.5%). Regarding Manchester triage, most nurses had training between 3 and 5 years (44.7%) and perform triage between 6 and 10 times a month (48.9%). Nurses have a positive perception about their decision-making skills in triage, with higher means in the skill Cognitive Characteristics/Confidence in Skill (4.94±0.420) and the lowest in Intuition (4.44±0.697). We observed significant correlations between the TDMI, the skills Cognitive Characteristics/Cognitive Skill Confidence, Intuition, Critical Thinking of the trier and the professional experience in the emergency department, as well as between the trier's age, experience in the profession and the skills cognitive characteristics and confidence. In summary, the triage decision-making skills are positively influenced by the professional experience in the emergency department, and the Cognitive Characteristics/Cognitive Skill Confidence skills are the most valued by the triage nurses.

Non-invasive and micro-invasive treatments to arrest active occlusal carious lesions in erupting permanent molars: A randomized clinical trial.

This study aimed to evaluate the efficacy of non-invasive and micro-invasive treatments on the arrest of occlusal enamel carious lesions in erupting permanent molars. This two-arm randomized clinical trial included 27 subjects, aged 5-11 years, with 64 erupting permanent molars presenting active occlusal enamel carious lesions (as assessed by the International Caries Detection and Assessment System [ICDAS]; scores 1-3). The sample was randomly assigned into two treatment groups: 1) resin-modified glass ionomer cement sealant (Clinpro XT Varnish; 3M ESPE) and 2) 4-week topical fluoride varnish application (Duraphat; Colgate). All children and parents received oral hygiene and dietary instructions. Teeth were evaluated at baseline and 3, 6, 9, and 12 months regarding the eruption stage, biofilm accumulation, as well as severity and activity of the carious lesions. The Kaplan-Meier method was used to evaluate the survival estimates for inactivation of the carious lesions for both treatment groups. Multivariate Cox regression models with shared frailty were performed to identify factors associated with the outcome (p < 0.05). After 12 months, 22% and 3% of the lesions treated with topical fluoride varnish and sealant, respectively remained active. The adjusted model demonstrated that younger children had a higher probability of active enamel carious lesions arresting (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.22-0.78; p=0.01). However, the probability of active enamel carious lesions arresting after sealant application was 8.85 times higher compared with fluoride varnish applications (p=0.01). Sealing is a more effective approach than fluoride varnish for arresting occlusal enamel carious lesions in erupting permanent molars.

Prevention of diabetes-associated fibrosis: Strategies in FcRn-targeted nanosystems for oral drug delivery.

Diabetes mellitus is a chronic disease with an elevated risk of micro- and macrovascular complications, such as fibrosis. To prevent diabetes-associated fibrosis, the symptomatology of diabetes must be controlled, which is commonly done by subcutaneous injection of antidiabetic peptides. To minimize the pain and distress associated with such injections, there is an urgent need for non-invasive oral transmucosal drug delivery strategies. However, orally administered peptide-based drugs are exposed to harsh conditions in the gastrointestinal tract and poorly cross the selective intestinal epithelium. Thus, targeting of drugs to receptors expressed in epithelial cells, such as the neonatal Fc receptor (FcRn), may therefore enhance uptake and transport through mucosal barriers. This review compiles how in-depth studies of FcRn biology and engineering of receptor-binding molecules may pave the way for design of new classes of FcRn-targeted nanosystems. Tailored strategies may open new avenues for oral drug delivery and provide better treatment options for diabetes and, consequently, fibrosis prevention.

The effect of hypergravity in intestinal permeability of nanoformulations and molecules.

The oral administration of drugs remains a challenge due to rapid enzymatic degradation and minimal absorption in the gastrointestinal tract. Mechanical forces, namely hypergravity, can interfere with cellular integrity and drug absorption, and there is no study describing its influence in the intestinal permeability. In this work, it was studied the effect of hypergravity on intestinal Caco-2 cells and its influence in the intestinal permeability of different nanoformulations and molecules. It was shown that the cellular metabolic activity and integrity were maintained after exposure to different gravity-levels (g-levels). Expression of important drug transporters and tight junctions' proteins was evaluated and, most proteins demonstrated a switch of behavior in their expression. Furthermore, paracellular transport of FITC-Dextran showed to significantly increase with hypergravity, which agrees with the decrease of transepithelial electrical resistance and the increase of claudin-2 at higher g-levels. The diffusion of camptothecin released from polymeric micelles revealed a significant decrease, which agrees with the increased expression of the P-gp observed with the increase in g-levels, responsible for pumping this drug out. The neonatal Fc receptor-mediated transport of albumin-functionalized nanoparticles loaded with insulin showed no significant changes when increasing the g-levels. Thus, this study supports the effect of hypergravity on intestinal permeability is dependent on the molecule studied and the mechanism by which it is absorbed in the intestine.

The potential of porcine ex vivo platform for intestinal permeability screening of FcRn-targeted drugs.

Conventionally, the intestinal permeability of drugs is evaluated using cell monolayer models that lack morphological, physiological and architectural features, as well as realistic neonatal Fc receptor (FcRn) expression. In addition, it is time-consuming, expensive and excessive to use a large number of mice for large-scale screening of FcRn-targeted candidates. For preclinical validation, it is critical to use suitable models that mimic the human intestine; the porcine ex vivo model is widely used for intestinal permeability studies, due to its physiological and anatomical similarities to humans. This study intended to analyze the potential to measure the intestinal permeability of FcRn-targeted substances using a porcine ex vivo platform, which is able to analyze 96 samples at the same time. In addition, the platform allows the screening of FcRn-targeting substances for transmucosal delivery, taking into consideration (cross-species) receptor-ligand binding kinetics. After analyzing the morphology of the porcine tissue, the FcRn expression across the gastrointestinal tract was verified. By studying the stomach, duodenum and jejunum, it was demonstrated that FcRn expression is maintained for up to 7 days. When evaluating the duodenum permeability of free engineered human albumin variants, it was shown that the variant with the mutation K573P (KP) is more efficiently transported. Given this, the porcine ex vivo platform was revealed to be a potential model for the screening of FcRn-targeted oral drug formulations.

Non-invasive and micro-invasive treatments to arrest active occlusal carious lesions in erupting permanent molars: A randomized clinical trial

Abstract: This study aimed to evaluate the efficacy of non-invasive and micro-invasive treatments on the arrest of occlusal enamel carious lesions in erupting permanent molars. This two-arm randomized clinical trial included 27 subjects, aged 5-11 years, with 64 erupting permanent molars presenting active occlusal enamel carious lesions (as assessed by the International Caries Detection and Assessment System [ICDAS]; scores 1-3). The sample was randomly assigned into two treatment groups: 1) resin-modified glass ionomer cement sealant (Clinpro XT Varnish; 3M ESPE) and 2) 4-week topical fluoride varnish application (Duraphat; Colgate). All children and parents received oral hygiene and dietary instructions. Teeth were evaluated at baseline and 3, 6, 9, and 12 months regarding the eruption stage, biofilm accumulation, as well as severity and activity of the carious lesions. The Kaplan-Meier method was used to evaluate the survival estimates for inactivation of the carious lesions for both treatment groups. Multivariate Cox regression models with shared frailty were performed to identify factors associated with the outcome (p < 0.05). After 12 months, 22% and 3% of the lesions treated with topical fluoride varnish and sealant, respectively remained active. The adjusted model demonstrated that younger children had a higher probability of active enamel carious lesions arresting (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.22-0.78; p=0.01). However, the probability of active enamel carious lesions arresting after sealant application was 8.85 times higher compared with fluoride varnish applications (p=0.01). Sealing is a more effective approach than fluoride varnish for arresting occlusal enamel carious lesions in erupting permanent molars.

Engineered albumin-functionalized nanoparticles for improved FcRn binding enhance oral delivery of insulin.

Oral delivery of biopharmaceuticals, as insulin, is hampered by rapid degradation and inefficient absorption in the gastrointestinal tract (GIT). To solve this, a new class of biodegradable poly(lactic-co-glycolic)-poly(ethylene glycol) (PLGA-PEG) mucodiffusive nanoparticles (NPs) was designed. Specifically, these were decorated with site-specific conjugated human albumin, engineered for improved pH dependent binding to the neonatal Fc receptor (FcRn), which naturally mediates transport of albumin across the intestinal epithelium. The designed NPs of monodisperse 150 nm in size were 10% loaded with insulin and their surface was successfully functionalized with human albumin. Importantly, the engineered albumin-functionalized NPs bound human FcRn favorably in a pH dependent manner and showed enhanced transport across polarized cell layers. When orally administered to human FcRn expressing mice induced with diabetes, a reduction of glycemia was measured as a function of receptor targeting, with up to around 40% reduction after 1 h post-delivery. Thus, biodegradable PLGA-PEG NPs decorated with human albumin for improved FcRn-dependent transport offer a novel attractive strategy for delivery of encapsulated biopharmaceuticals across intestinal barriers.

SARS-CoV-2 and diabetes: New challenges for the disease.

A novel small enveloped RNA virus with the typical characteristic of the family to which it belongs, a crown, hence the name coronavirus, appeared in December 2019 in Wuhan, China, and subdued the world to its influence. The particular severity of the disease and higher mortality rates in patients with associated morbidities, including hypertension, obesity and diabetes, increases the concern over the consequences of this pandemic. In this review, the features of SARS-CoV-2 will be addressed, as well as the reasons why it poses a particular challenge to diabetic patients. We will also highlight the recent treatment strategies being explored to control this pandemic. Emerging evidence demonstrates that the correct management of diabetes in those patients infected with SARS-CoV-2 is of utmost importance for the viral disease progression, therefore, the importance of blood glucose control will also be addressed.

An intact C-terminal end of albumin is required for its long half-life in humans.

Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.

Sleep bruxism and oral health-related quality of life in children: A systematic review.

Sleep bruxism (SB) is a masticatory muscle activity during sleep that can cause several consequences to the stomatognathic system. This systematic review investigated the impact of SB on oral health-related quality of life (OHRQoL) of 0- to 6-year-old children. Literature search was undertaken through PubMed/MEDLINE, LILACS, Scopus, TRIP, Livivo databases, and grey literature. The search was conducted with no publication year or language limits. Two reviewers independently selected the studies, extracted the data and assessed the risk of bias. The quality of evidence was assessed using GRADE. From 185 potentially eligible studies, three were included in the review. All studies were conducted in Brazil, published between 2015 and 2017, and used the B-ECOHIS instrument to evaluate OHRQoL. Two studies found no association between SB and OHRQoL, whereas one showed a significant negative impact of SB on the OHRQoL of children. SB was associated with respiratory problems, presence of tooth wear, dental caries, malocclusion as well as income and pacifier use. Risk of bias ranged from moderate to high, and the quality of evidence was judged as very low. The evidence is currently insufficient for definitive conclusions about the impact of SB on OHRQoL of children.

Strategies for the enhanced intracellular delivery of nanomaterials.

The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.

Chemical modification of drug molecules as strategy to reduce interactions with mucus.

Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exerting any physiologic affect. Envisaging a better pharmacokinetics profile, chemical modifications, to render drug a more mucopenetrating character, have been introduced to drug molecules backbone towards more effective therapies. Mucus penetration increases when drug molecules are provided with net-neutral charge, when they are conjugated with mucolytic agents and through modifications that makes them resistant to enzymes present in mucus, with the overall increase of their hydrophilicity and the decrease of their molecular weight. All of these characteristics act as a whole and influence each other so they must be well thought when drug molecules are being designed for mucosal delivery.

Development and characterization of crosslinked hyaluronic acid polymeric films for use in coating processes.

The aim of this work was to develop and characterize new hyaluronic acid-based responsive materials for film coating of solid dosage forms. Crosslinking of hyaluronic acid with trisodium trimetaphosphate was performed under controlled alkaline aqueous environment. The films were produced through casting process by mixing crosslinked or bare biopolymer in aqueous dispersion of ethylcellulose, at different proportions. Films were further characterized regarding morphology by scanning electron microscopy, robustness by permeation to water vapor transmission, and ability to hydrate in simulated gastric and intestinal physiological fluids. The safety and biocompatibility of films were assessed against Caco-2 and HT29-MTX intestinal cells. The permeation to water vapor transmission was favored by increasing hyaluronic acid content in the final formulation. When in simulated gastric fluid, films exhibited lower hydration ability compared to more extensive hydration in simulated intestinal fluids. Simultaneously, in simulated intestinal fluids, films partially lost weight, revealing ability for preventing drug release at gastric pH, but tailoring the release at higher intestinal pH. The physiochemical characterization suggests thermal stability of films and physical interaction between compounds of formulation. Lastly, cytotoxicity tests demonstrated that films and individual components of the formulations, when incubated for 4h, were safe for intestinal cells Overall, these evidences suggest that hyaluronic acid-based responsive films, applied as coating material of oral solid dosage forms, can prevent the premature release of drugs in harsh stomach conditions, but control the release it in gastrointestinal tract distal portion, assuring safety to intestinal mucosa.

Effect of the Freezing Step in the Stability and Bioactivity of Protein-Loaded PLGA Nanoparticles Upon Lyophilization.

PURPOSE: The freezing step in lyophilization is the most determinant for the quality of biopharmaceutics. Using insulin as model of therapeutic protein, our aim was to evaluate the freezing effect in the stability and bioactivity of insulin-loaded PLGA nanoparticles. The performance of trehalose, sucrose and sorbitol as cryoprotectants was evaluated. METHODS: Cryoprotectants were co-encapsulated with insulin into PLGA nanoparticles and lyophilized using an optimized cycle with freezing at -80°C, in liquid nitrogen, or ramped cooling at -40°C. Upon lyophilization, the stability of protein structure and in vivo bioactivity were assessed. RESULTS: Insulin was co-encapsulated with cryoprotectants resulting in particles of 243-394 nm, zeta potential of -32 to -35 mV, and an association efficiency above 90%. The cryoprotectants were crucial to mitigate the freezing stresses and better stabilize the protein. The insulin structure maintenance was evident and close to 90%. Trehalose co-encapsulated insulin-loaded PLGA nanoparticles demonstrated enhanced hypoglycemic effect, comparatively to nanoparticles without cryoprotectant and added with trehalose, due to a superior insulin stabilization and bioactivity. CONCLUSIONS: The freezing process may be detrimental to the structure of protein loaded into nanoparticles, with negative consequences to bioactivity. The co-encapsulation of cryoprotectants mitigated the freezing stresses with benefits to protein bioactivity.

Xanthohumol impairs glucose uptake by a human first-trimester extravillous trophoblast cell line (HTR-8/SVneo cells) and impacts the process of placentation.

In this study, we aimed to investigate modulation of glucose uptake by the HTR-8/SVneo human first-trimester extravillous trophoblast cell line by a series of compounds and to study its consequences upon cell proliferation, viability and migration. We observed that uptake of (3)H-deoxy-d-glucose ((3)H-DG; 10 nM) was time-dependent, saturable, inhibited by cytochalasin B (50 and 100 µM), phloretin (0.5 mM) and phloridzin (1 mM), insulin-insensitive and sodium-independent. In the short term (30 min), neither 5-HT (100-1000 µM), melatonin (10 nM) nor the drugs of abuse ethanol (100 mM), nicotine (100 µM), cocaine (25 µM), amphetamine (10-25 µM) and 3,4-methylenedioxy-N-methamphetamine (10 µM) affected (3)H-DG uptake, while dexamethasone (100-1000 µM), fluoxetine (100-300 µM), quercetin, epigallocatechin-3-gallate (30-1000 µM), xanthohumol (XH) and resveratrol (1-500 µM) decreased it. XH was the most potent inhibitor [IC50 = 3.55 (1.37-9.20) µM] of (3)H-DG uptake, behaving as a non-competitive inhibitor of (3)H-DG uptake, both after short- and long-term (24 h) treatment. The effect of XH (5 µM; 24 h) upon (3)H-DG uptake involved mammalian target of rapamycin, tyrosine kinases and c-Jun N-terminal kinases intracellular pathways. Moreover, XH appeared to decrease cellular uptake of lactate due to inhibition of the monocarboxylate transporter 1. Additionally, XH (24 h; 5 µM) decreased cell viability, proliferation, culture growth and migration. The effects of XH upon cell viability and culture growth, but not the antimigratory effect, were mimicked by low extracellular glucose conditions and reversed by high extracellular glucose conditions. We thus suggest that XH, by inhibiting glucose cellular uptake and impairing HTR-8/SVneo cell viability and proliferation, may have a deleterious impact in the process of placentation.