ADAM10 as a biomarker for Alzheimer's disease: A systematic review.

BACKGROUND: Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-ß peptide (Aß), one of the pathological hallmarks of Alzheimer's disease (AD). OBJECTIVE: To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD. METHODS: A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239). RESULTS: Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection. CONCLUSION: Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.

Effects of 1,3-propanediol associated, or not, with butylene glycol and/or glycerol on skin hydration and skin barrier function.

OBJECTIVE: This study aimed to assess the effect of 1,3-propanediol at different concentrations (5%, 10%, or 15%), either applied alone or in combination with butylene glycol (BG) (5%) and/or glycerol (5%), on skin hydration and skin barrier function. The measurements were conducted using capacitance to determine skin hydration and trans epidermal water loss (TEWL) rates to evaluate skin barrier function. METHODS: A total of 30 healthy female subjects participated in the study. Capacitance and TEWL measurements were conducted at multiple time points, including before application and at 15 min, 2 and 8 h after the humectants were applied to the forearms of the subjects. All the subjects provided written informed consent. RESULTS: The 1,3-propanediol in all concentrations and in all combinations (with BG and/or glycerol) increased skin hydration and improved skin barrier function 15 min, 2 and 8 h after application. Glycerol increased the hydration performance of 1,3-propanediol. The application of 1,3-propanediol at a concentration of 15%, either alone or in combination with other humectants, reduced the TEWL to a greater extent than lower concentrations of 1,3-propanediol. Furthermore, the addition of glycerol to 1,3-propanediol 15% improved the skin barrier and reduced TEWL when compared with 1,3-propanediol alone and with the combination of 1,3-propanediol + BG. CONCLUSION: The humectants significantly improved skin hydration and reduced TEWL throughout the 8-h time course. The increase in 1,3-propanediol concentration, as well as its combination with glycerol, provided a greater benefit to the skin, improving both hydration and the skin barrier function.

OBJECTIF: Cette étude visait à évaluer l'effet sur l'hydratation de la peau et la fonction de barrière cutanée du 1,3-propanediol à différentes concentrations (5 %, 10 % ou 15 %), appliqué seul ou en association avec du butylène glycol (5 %) et/ou du glycérol (5 %). Les mesures ont été effectuées à l'aide de la capacitance pour déterminer l'hydratation de la peau et les taux de perte d'eau transépidermique (Trans Epidermal Water Loss, TEWL) pour évaluer la fonction de barrière cutanée. MÉTHODES: Au total, 30 sujets de sexe féminin en bonne santé ont participé à l'étude. Les mesures de la capacitance et de la TEWL ont été effectuées à plusieurs moments, y compris avant l'application, 15 minutes, 2 heures et 8 heures après l'application des produits humectant sur les avant-bras des sujets. Tous les sujets ont fourni un consentement éclairé écrit. RÉSULTATS: Le 1,3-propanediol, à toutes les concentrations et dans toutes les associations (avec le butylène glycol et/ou le glycérol), a augmenté l'hydratation de la peau et amélioré la fonction de barrière cutanée à 15 minutes, 2 heures et 8 heures après l'application. Le glycérol a augmenté les performances d'hydratation du 1,3-propanediol. L'application de 1,3-propanediol à une concentration de 15 %, seul ou en association avec d'autres produits humectant, a réduit la TEWL dans une plus grande mesure que des concentrations inférieures de 1,3-propanediol. En outre, l'ajout de glycérol au 1,3-propanediol 15 % a amélioré la barrière cutanée et réduit la TEWL par rapport au 1,3-propanediol seul et à l'association 1,3-propanediol + butylène glycol. CONCLUSION: Les produits humectant ont significativement amélioré l'hydratation de la peau et réduit la TEWL tout au long des 8 heures. L'augmentation de la concentration de 1,3-propanediol, ainsi que son association avec le glycérol, ont apporté un plus grand bénéfice à la peau, améliorant à la fois l'hydratation et la fonction de barrière cutanée.

Choline chloride-based deep eutectic solvent as an inhibitor of metalloproteases (collagenase and elastase) in cosmetic formulation.

Green chemistry and engineering are potential alternatives for achieving higher sustainability and lower generation of hazardous compounds in chemical product design, production, and use. Deep Eutectic Solvents (DES) are characterized as green solvents and have become increasingly attractive due to their characteristic design solvents. In this work, two DES (choline chloride (ChCl)/glycerol and ChCl/Urea), aqueous solutions of the DES-forming components, and green tea extracts obtained with DES were used as anti-ageing active in cosmetic products using in vitro tests to inhibit extracellular matrix metalloproteases (such as collagenase and elastase). Finally, the stability of the formulations with DES as a cosmetic active was also evaluated. The results showed that DES based on ChCl/Urea and ChCl/glycerol exhibited remarkable inhibition values of collagenase (91.1 and 92.7%, respectively) and elastase (49.8 and 45.7%, respectively). However, pure urea displayed better inhibition values (66%) for elastase, possibly due to its direct contribution to intramolecular hydrogen bonds. ChCl/glycerol showed remarkable stability in the average cube diameter values, which may indicate no change in the conformation of the micellar structure of the cosmetic formulation. Moreover, the formulation containing this DES remained stable at room temperature. Given the remarkable results, DES can be applied in cosmetic products for anti-ageing purposes.

Physical activity measured with an accelerometer in dogs following extracapsular stabilisation to treat cranial cruciate ligament rupture.

OBJECTIVES: To quantify the physical activity levels in dogs with cranial cruciate ligament rupture before and after lateral fabellar suture stabilisation surgery. MATERIALS AND METHODS: Seventeen dogs (mean weight, 12.3±5.1 kg) with unilateral cranial cruciate ligament rupture were fitted with an accelerometer for seven consecutive days at four different time points: before surgery (T0), one (T1), three (T3) and six (T6) months after surgery. The total activity and times spent in sedentary activity, light to moderate activity and vigorous activity were recorded by the accelerometer, and preoperative and postoperative data were compared. At all time points, dogs underwent clinical evaluations (lameness score, stifle pain score and thigh circumference) and their owners were asked to respond to questionnaires to subjectively score the physical activity and quality of life of the dogs. RESULTS: At the four time points, the dogs spent between 21.2 and 21.4 hours on sedentary behaviour, 2.3 and 2.5 hours performing light to moderate activity, and 13 to 15 minutes performing vigorous activity. There was no increase in physical activity variables or decrease in sedentary behaviour over time. Lameness scores, pain score and dogs' quality of life improved significantly during the postoperative period. At T6, 17 (100%) of 17 dogs presented no lameness, 16 (94%) of 17 dogs presented no stifle pain, 16 (94%) of 17 owners rated the quality of life as very good and excellent, and 16 (100%) of 16 owners reported a total return to normal activity levels. CLINICAL SIGNIFICANCE: The clinical recovery after extracapsular stabilisation of the stifle joint was not associated with a spontaneous increase in physical activity or a decrease in sedentary behaviour.

Determinants of menstrual cup use among undergraduate medical students: A cross-sectional study.

OBJECTIVE: To identify the determinants of menstrual cup use among medical students in Brazil. METHODS: A cross-sectional study with an online survey regularly applied to matriculate women from Medical School in January 2021. RESULTS: Of 277 women, 164 participated. The mean age was 22.26 ± 3.21 years. In all 136 women preferred external pads, 60 internal pads, 28 menstrual cups, and 11 did not use. Using a 1-10 scale, price, efficacy, sustainability, practice, vaginal health status, hygiene, and importance of internal genital integrity were investigated. Thirty-seven (22.56%) women related the use of menstrual cups in the last year. Using any method to reduce menstruation had an adjusted odds ratio (aOR) of 0.310 (95% confidence interval [CI] 0.122-0.787). Concern about the environmental biodegradation had an aOR of 6.369 (95% CI 1.372-29.562); concern about intimal health had an aOR 1.996 (95% CI 1.183-3.368); and concern about internal genital integrity had an aOR of 0.824 (95% CI 0.682-0.995) for menstrual cup use. CONCLUSION: The significant independent factors for the use or adherence to menstrual cups were: women using a method to reduce their menstrual flow; concerning biodegradation; concerning vaginal health; with no concerns about manipulating their genitalia. The menstrual cup was used by 22.56% of a medical school in Brazil among undergraduate women.

Skin occlusive performance: Sustainable alternatives for petrolatum in skincare formulations.

BACKGROUND: The emollients are important ingredients used in skincare formulations that can act as moisturizing agents through their occlusive potential, preventing skin water loss. Consumer interest in natural and sustainable products has grown considerably in the last few years, requiring efforts from the cosmetic industry to design products with raw materials of natural, organic, and sustainable origin. Thus, it is essential to improve the knowledge about the behavior of cosmetic raw materials that can be used as sustainable alternatives to synthetic ingredients. AIM: This work aimed to evaluate the occlusive performance of different vegetable oils used as emollients in skincare cosmetics, through comparative analysis with petrolatum, a synthetic emollient with a high occlusive skin potential. METHOD: The study included 80 healthy female adult volunteers. TEWL measurements were performed before and after 15 min, 2 and 6 h of emollients application on the forearms of the research participants. All research participants provided written informed consent. RESULTS: The results obtained showed that the vegetable oils were effective in providing an occlusive effect on the skin. When compared to the petrolatum, the vegetable oils did not provide a high immediate skin occlusion effect. However, most of them showed a skin occlusion performance comparable to petrolatum throughout the 6 h time course. CONCLUSION: Vegetable oils can be used as a sustainable alternative to synthetic emollients, and they are promising in replacing petrolatum in skincare formulations with respect to the occlusion effect of the skin. The vegetable oils did not provide a high immediate skin occlusion effect (15 min post-application) as the petrolatum, which is known to have increased occlusion properties. However, most of them showed a skin occlusion performance comparable to petrolatum throughout the 6-hour time course.

Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that can be activated by structurally diverse compounds arising from the environment and the microbiota and host metabolism. Expanding evidence has been shown that the modulation of the canonical pathway of AHR occurs during several chronic diseases and that its abrogation might be of clinical interest for metabolic and inflammatory pathological processes. However, most of the evidence on the pharmacological abrogation of the AHR-CYP1A1 axis has been reported in vitro, and therefore, guidance for in vivo studies is needed. In this review, we cover the state-of-the-art of the pharmacodynamic and pharmacokinetic properties of AHR antagonists and CYP1A1 inhibitors in different in vivo rodent (mouse or rat) models of disease. This review will serve as a road map for those researchers embracing this emerging therapeutic area targeting the AHR. Moreover, it is a timely opportunity as the first AHR antagonists have recently entered the clinical stage of drug development.

Investigator Initiated Clinical Trials (IICTs): A Systematic Search in Registries to Compare the Czech Republic and Portugal in Terms of Funding Policies and Scientific Outcomes.

OBJECTIVES: Clinical trials provide one of the highest levels of evidence to support medical practice. Investigator initiated clinical trials (IICTs) answer relevant questions in clinical practice that may not be addressed by industry. For the first time, two European Countries are compared in terms of IICTs, respective funders and publications, envisaging to inspire others to use similar indicators to assess clinical research outcomes. METHODS: A retrospective systematic search of registered IICTs from 2004 to 2017, using four clinical trials registries was carried out in two European countries with similar population, GDP, HDI and medical schools but with different governmental models to fund clinical research. Each IICT was screened for sponsors, funders, type of intervention and associated publications, once completed. RESULTS: IICTs involving the Czech Republic and Portugal were n = 439 (42% with hospitals as sponsors) and n = 328 (47% with universities as sponsors), respectively. The Czech Republic and Portuguese funding agencies supported respectively 61 and 27 IICTs. Among these, trials with medicinal products represent 52% in Czech Republic and 4% in Portugal. In the first, a higher percentage of IICTs' publications in high impact factor journals with national investigators as authors was observed, when compared to Portugal (75% vs 15%). CONCLUSION: The better performance in clinical research by Czech Republic might be related to the existence of specific and periodic funding for clinical research, although further data are still needed to confirm this relationship. In upcoming years, the indicators used herein might be useful to tracking clinical research outcomes in these and other European countries.

Yellow grease in sheep diets: intake and digestibility / [Óleo residual de fritura em dietas para ovinos: consumo e digestibilidade]

This study aimed to assess the effects of yellow grease supplementation on the intake, digestibility, and nitrogen balance in sheep. Twenty Santa Inês lambs with a mean age of 95 ± 10 d and body weight of 19.29 ± 3.17kg were evaluated in a completely randomized design. The diets were supplemented with oil at concentrations of 0, 20, 40, 60, and 80 gkg-1 of dry matter (DM) of the concentrate. The diets were based on roughage and concentrate (50:50). The experimental period lasted 19 d and included 14 adaptation days and five collection days for the total supplied diet, orts, feces, and urine. Supplementation with yellow grease had no significant effect on the intake of DM, crude protein (CP), neutral detergent fiber (NDF), or non-fiber carbohydrates (NFC). However, the ether extract (EE) intake increased linearly with supplementation of yellow grease. Moreover, no effect was observed for DM, CP, NDF, and NFC digestibility and nitrogen balance. EE digestibility increased linearly with the yellow grease dietary supplementation. Thus, sheep dietary supplementation with yellow grease may be used at a level of up to 80 gkg-1 of DM of concentrate without impairing nutrient intake and digestibility.(AU)

Objetivou-se, com o estudo, avaliar os efeitos do óleo residual de fritura, em dietas para ovinos, sob o consumo, a digestibilidade e o balanço de nitrogênio. Foram utilizados 20 cordeiros Santa Inês, com idade de 95 ± 10 dias e peso corporal de 19,29 ± 3,17kg, em delineamento inteiramente ao acaso. As dietas continham óleo de fritura nas concentrações de 0; 20; 40; 60 e 80gkg-1 da matéria seca (MS) do concentrado. As dietas tinham relação volumoso:concentrado de 50:50. O período experimental foi de 19 dias, incluindo 14 dias em adaptação e cinco dias de coleta do fornecido, das sobras, das fezes e da urina. A suplementação com óleo de fritura não alterou o consumo de MS, proteína bruta (PB), matéria orgânica (MO), fibra em detergente neutro (FDN) e carboidratos não fibrosos (CNF). Entretanto, o consumo de extrato etéreo (EE) aumentou com a inclusão do óleo. Não foi observado efeito na digestibilidade da MS, da PB, da FDN, dos CNF e no balanço de nitrogênio. A digestibilidade do EE aumentou com a inclusão do óleo. Assim, a inclusão de óleo de fritura em dietas para ovinos pode ser utilizada em até 80gkg-1 da MS do concentrado, sem limitar ingestão e digestibilidade dos nutrientes.(AU)

High-frequency ultrasound as a scientific tool for skin imaging analysis.

Ultrasonic imaging is one of the most important diagnostic tools in clinical medicine due to its cost, availability and good correlation with pathological results. High-frequency ultrasound (HFUS) is a technique used in skin science that has been little explored, especially in comparison with other sites and imaging techniques. HFUS shows real-time images of the skin layers, appendages and skin lesions in vivo and can significantly contribute to advances in skin science. This review summarizes the potential applications of HFUS in dermatology and cosmetology, with a focus on quantitative tools that can be used to assess various skin conditions. Our findings showed that HFUS imaging is a reproducible and powerful tool for the diagnosis, clinical management and therapy monitoring of skin conditions. It is also a helpful tool for assessing the performance of dermatological products. This technique may eventually become essential for evaluating the performance of dermatological and cosmetic products.

Skin effect of facial cleansing combined with an electric sonic device.

BACKGROUND: New technologies, such as sonic devices, have been developed to optimize the skin cleansing process and improve its efficiency. To evaluate the effectiveness of these cosmetic procedures, skin bioengineering is an objective method to assess the biophysical parameters of the skin. AIMS: This study aimed to assess the effect of facial cleansing on the physiological properties of the skin by comparing a cleansing process with cosmetic product applied manually to cleansing with cosmetic product associated with the use of an electric sonic device. PATIENTS/METHODS: A gentle skin cleanser was applied to the entire face of 12 subjects; the sonic device was used on one half of the face and the manual process was performed on the other half. Instrumental skin analyses included sebummetry, corneometry, transepidermal water loss (TEWL), infrared thermography, and high-frequency ultrasound and were measured before and up to 90 min after cleansing. Results were compared using two-way ANOVA and Friedman tests. RESULTS: Data obtained from the statistical analysis of sebummetry, TEWL, thermography, and ultrasound parameters did not show any significant difference. When assessing the corneometry parameters, a significant reduction in hydration values (17.19%) was observed in the manual cleansing area, while the values remained similar to baseline values in the area where the sonic device was used. CONCLUSION: The cleansing process with a sonic device did not cause a significant hydration reduction, suggesting better preservation of skin homeostasis when compared to manual cleansing.

Target action of antioxidants using iontophoresis.

BACKGROUND: The use of antioxidants in applications for topical use seems promising, however, many studies must be performed to ensure processes and products that can effectively bring benefits to combat the action of free radicals in the skin. For topical antioxidants to be effective against free radicals from the skin, it is essential that the antioxidants compounds permeate the different skin layers, to reach deeper layers of the epidermis in active form and stay there for a sufficient time to cause the beneficial effects. AIM: This work aimed to evaluate the antioxidant action of formulations with phenolic compounds as well as to comprehend the skin retention profile of these actives. METHODS: The antioxidant potential was recognized with isolated phenolic acids (gallic, caffeic, and ferulic acid) or in combinations, using different in vitro methods (DPPH ABTS , FRAP , ß-carotene/linoleic acid system and ORAC). The skin retention study was performed through in vitro assay with Franz's diffusion cell associating, or not, the cathodic iontophoresis. RESULTS: Gallic acid showed the greatest antioxidant activity and was selected for a study of skin permeation following gel application to porcine skin, with or without cathodic iontophoresis. Gallic acid retention in deeper skin layers was promoted by iontophoresis, and increased skin antioxidant activity was detected after only 20 min of iontophoresis. The present study demonstrated the importance of polymeric gelling agents for optimizing the antioxidant activity. CONCLUSION: The cathodic iontophoresis represents a promising strategy to promote a target action of antioxidants in the skin.

Development and cathodic iontophoretic permeation evaluation of liquid crystalline systems provided of retinoic acid microparticles.

BACKGROUND: The intracellular form of action of retinoids requires these agents to reach deeper layers of the skin with viable cells to ensure therapeutic efficiency. However, studies on swine skin models show that some retinoids have low skin permeability. Thus, the association of innovative formulations with technological strategies involving physical permeation promoters can be employed to increase the permeability of this active, ensuring a targeting effect of the active. AIMS: In this study, it was proposed the development and evaluation of the release and permeation profile of liquid crystalline systems with retinoic acid polymeric microparticles under passive or iontophoretic diffusional conditions. METHODS: For this study, release, permeation, and diffusional characterization assays were employed using the Franz diffusion cell model, associating or not the cathodic iontophoresis. RESULTS: Retinoic acid was considered stable in front of the electric current of 0.5mA/cm2 , because it did not show significant degradation (with maintenance from 96.03% to 98.57%), indicating the viability of such agents to be applied with iontophoresis. Controlled release profile was evidenced for microencapsulated systems. Comparatively, formulations F1, F3, and F5 presented a significantly higher RA release profile when compared to formulations with retinoic acid microencapsulated. A significant increase was observed in the absolute amount of RA retained in the skin with cathodic iontophoresis in all proposed formulations (P < .01). The increase was up to two times in relation to the passive condition. CONCLUSIONS: The combination of iontophoresis technique with application of retinoic acid and microencapsulated retinoic acid allows the penetration of the active ingredient to deeper layers of the skin.

Experiências de mulheres ao vivenciarem uma gravidez entre 35 e 45 anos de idade / Experiences of women who faced a pregnancy between 35 and 45 years of age / Experiencias de mujeres al enfrentar un embarazo entre 35 y 40 años

Objetivo: identificar a experiência de mulheres ao vivenciarem uma gravidez tardia. Método: estudo descritivo, quantitativo, desenvolvido no município de Ouro Velho-PB, com mulheres na faixa etária entre 35 a 45 anos de idade. A amostra gerou em torno de 19 mulheres que engravidaram nesta faixa etária, cadastradas na Unidade Básica de Saúde da Família do município. Resultados: observou-se que a maioria estava entre 35 a 40 anos (58%), casadas, pardas e ensino superior, entretanto, a gravidez tardia possibilitou significados na vida destas mulheres, permeadas de sentimentos de satisfação pessoal, familiar, possibilitando maior segurança na relação com o companheiro, família e bebê. Conclusão: identificou-se complicações como hipertensão, prematuridade, aborto e pós-datismo, que influenciaram no tipo da via de parto, sendo a cesariana a de maior evidência. O preparo psicológico para a maternidade nessa faixa etária é acompanhado de sentimentos de desejo, alegria, ansiedade e medo do desconhecido

Objetivo: Identificar la experiencia de las mujeres al enfrentar un embarazo tardío. Método: Estudio descriptivo y cuantitativo, desarrollado en la ciudad de Ouro Velho-PB, con mujeres de entre 35 y 45 años. La muestra generó alrededor de 19 mujeres que quedaron embarazadas en esta franja etaria, registradas en la Unidad Básica de Salud Familiar de dicha ciudad. Resultados: Notamos que la mayoría tenían entre 35 y 40 (58%), casadas, de raza mixta y educación superior; sin embargo, el embarazo tardío permitió significados en la vida de estas mujeres, impregnados de sentimientos de satisfacción personal y familiar, lo que permitió una mayor seguridad en la relación con el compañero, la familia y el bebé. Conclusión: Identificamos complicaciones, como hipertensión, prematuridad, aborto y postdatismo, que influyeron en el tipo de vía de parto, siendo la cesárea la más frecuente. La preparación psicológica para la maternidad en esta franja etaria se entrelaza con sentimientos de deseo, alegría, ansiedad y miedo a lo desconocido

Objetivo: Identificar la experiencia de las mujeres al enfrentar un embarazo tardío. Método: Estudio descriptivo y cuantitativo, desarrollado en la ciudad de Ouro Velho-PB, con mujeres de entre 35 y 45 años. La muestra generó alrededor de 19 mujeres que quedaron embarazadas en esta franja etaria, registradas en la Unidad Básica de Salud Familiar de dicha ciudad. Resultados: Notamos que la mayoría tenían entre 35 y 40 (58%), casadas, de raza mixta y educación superior; sin embargo, el embarazo tardío permitió significados en la vida de estas mujeres, impregnados de sentimientos de satisfacción personal y familiar, lo que permitió una mayor seguridad en la relación con el compañero, la familia y el bebé. Conclusión: Identificamos complicaciones, como hipertensión, prematuridad, aborto y postdatismo, que influyeron en el tipo de vía de parto, siendo la cesárea la más frecuente. La preparación psicológica para la maternidad en esta franja etaria se entrelaza con sentimientos de deseo, alegría, ansiedad y miedo a lo desconocido

European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

Effect of iontophoresis on fluoride uptake in enamel with artificial caries lesion.

Iontophoresis is a noninvasive technique, based on the application of a constant low-intensity electric current to facilitate the release of a variety of drugs, whether ionized or not, through biological membranes. The objective of this research was to evaluate the effect of iontophoresis using different electric current intensities on the uptake of fluoride in dental enamel with artificial caries lesions. In this in vitro operator-blind experiment, bovine enamel blocks (n = 10/group) with caries-like lesions and predetermined surface hardness were randomized into 6 groups: placebo gel without fluoride applied with a current of 0.8 mA (negative control), 2% NaF gel without application of any current, and 2% NaF gel applied with currents of 0.1, 0.2, 0.4 and 0.8 mA. Cathodic iontophoresis was applied for 4 min. The concentration of loosely bound fluoride (calcium fluoride) and firmly bound fluoride (fluorapatite) was determined. The results were analyzed by the nonparametric Kruskal-Wallis and Dunn tests. Iontophoresis at 0.8 mA, combined with the application of fluoridated gel (2% NaF), increased fluoride uptake in enamel with caries-like lesions, as either calcium fluoride or fluorapatite.

O impacto da aprendizagem interprofissional na pneumonia associada à ventilação: implementação de bundles em uma unidade de cuidados intensivos / The impact of the interprofessional learning in ventilator-associated pneumonia: bundles implementation in an intensive care unit

Objetivo: verificar o impacto dos bundles e o aprendizado interprofissional na prevenção de pneumonia associada à ventilação mecânica de uma unidade de terapia intensiva (UTI). Método: estudo quasi-experimental realizado em uma UTI de um hospital público de Diamantina, Minas Gerais. Foram incluídos neste estudo 56 profissionais que prestavam assistência direta a pacientes em ventilação mecânica. A coleta de dados ocorreu em três fases: pré-intervenção, que consistiu em observação direta e entrevista; intervenção, na qual o treinamento foi realizado por meio de simulações clínicas; e pós-intervenção, na qual foi avaliado o impacto das estratégias implementadas por observação direta. As diferenças entre os grupos pré- e pós-intervenção foram avaliadas pelo teste de McNemar. Foi utilizado um nível alfa de 0,05 definido a priori, e a correção de Bonferroni determinou significância estatística para o caso de comparações múltiplas. Resultados: após a intervenção, houve aumento da adesão à pressão endotraqueal do cuff (8,10%), interrupção diária da sedação (16,67%), e aspiração subglótica (18,75%). As associações entre categoria profissional versus ausência de aspiração, posicionamento da cabeceira da cama, frequência de higiene bucal, e tipo de higiene das mãos após a intervenção foram significativas (p < 0,0083). Conclusões: ainda existe uma lacuna a ser detectada na implementação do bundle e o impacto positivo gerado pelo conhecimento interprofissional, principalmente porque não é imediato, mas a longo prazo, para obter o feedback desejado. (AU)

Objective: to verify the impact of the bundles and the interprofessional learning for the prevention of mechanical ventilation-associated pneumonia of an intensive care unit (ICU). Method: This was a quasi-experimental study performed in an ICU of a public hospital in Diamantina, Minas Gerais. Were included in this study 56 professionals who provided direct assistance to patients in mechanical ventilation. The data collection took place in three phases: pre-intervention, which consisted of direct observation and interview; intervention, in which training was performed through clinical simulations; and post-intervention, in which the impact of the strategies implemented through direct observation, was evaluated. Differences between pre and post groups were assessed using McNemar's test. An alpha level of 0.05 set a priori was used, and a Bonferroni correction determined statistical significance for the case of multiple comparisons. Results: After the intervention, there was increased adherence to endotracheal cuff pressure (8.10%), daily interruption of sedation (16.67%) and subglottic aspiration (18.75%). It was significant (p < 0,0083) in the associations between the professional category versus non-aspiration, bed head positioning, oral hygiene frequency and the type of hand hygiene after intervention. Conclusions: There is still a gap to be detected in the bundle implementation and the positive impact generated by the inter-professional knowledge, mainly because it is not immediate but in the long term to obtain the desired feedback. (AU)

Objetivo: verificar el impacto de los bundles y el aprendizaje interprofesional para la prevención de la neumonía asociada a la ventilación mecánica de una unidad de cuidados intensivos (UCI). Método: Este fue un estudio cuasi experimental realizado en una UCI de un hospital público en Diamantina, Minas Gerais. Se incluyeron en este estudio 56 profesionales que prestaron asistencia directa a los pacientes en ventilación mecánica. La recolección de datos se realizó en tres fases: pre-intervención, que consistió en observación directa y entrevista; intervención, en la cual se realizó entrenamiento por medio de simulaciones clínicas; y post-intervención, en que se evaluó el impacto de las estrategias de observación directa. Las diferencias entre los grupos pre y post se evaluaron mediante la prueba de McNemar. Se usó un nivel alfa de 0,05 a priori, y se usó una corrección de Bonferroni para determinar la significación estadística en el caso de comparaciones múltiples. Resultados: Después de la intervención, hubo aumento de la adhesión al monitoreo de la presión del cuff endotraqueal (8,10%), interrupción diaria de la sedación (16,67%) y aspiración subglótica (18,75%). Fue significativa (p < 0,0083) las asociaciones entre la categoría profesional frente a la no aspiración, la posición de la cabecera de la cama, la frecuencia de higiene oral y el tipo de higiene de las manos después de la intervención. Conclusiones: Aún existe una laguna a ser detectada en la implantación del bundle y el impacto positivo generado por el conocimiento interprofesional, principalmente por no ser inmediato, pero a largo plazo, para obtener el feedback deseado. (AU)

Effect of iontophoresis on fluoride uptake in enamel with artificial caries lesion

Abstract: Iontophoresis is a noninvasive technique, based on the application of a constant low-intensity electric current to facilitate the release of a variety of drugs, whether ionized or not, through biological membranes. The objective of this research was to evaluate the effect of iontophoresis using different electric current intensities on the uptake of fluoride in dental enamel with artificial caries lesions. In this in vitro operator-blind experiment, bovine enamel blocks (n = 10/group) with caries-like lesions and predetermined surface hardness were randomized into 6 groups: placebo gel without fluoride applied with a current of 0.8 mA (negative control), 2% NaF gel without application of any current, and 2% NaF gel applied with currents of 0.1, 0.2, 0.4 and 0.8 mA. Cathodic iontophoresis was applied for 4 min. The concentration of loosely bound fluoride (calcium fluoride) and firmly bound fluoride (fluorapatite) was determined. The results were analyzed by the nonparametric Kruskal-Wallis and Dunn tests. Iontophoresis at 0.8 mA, combined with the application of fluoridated gel (2% NaF), increased fluoride uptake in enamel with caries-like lesions, as either calcium fluoride or fluorapatite.

Is There a Relationship Between Optimal Cerebral Perfusion Pressure-Guided Management and PaO2/FiO2 Ratio After Severe Traumatic Brain Injury?

OBJECTIVE: Severe traumatic brain injury (TBI) management has been associated with adult respiratory distress syndrome (ARDS) in previous literature. We aimed to investigate the relationships between optimal CPP-guided management, ventilation parameters over time and outcome after severe TBI. MATERIALS AND METHODS: We performed retrospective analysis of recorded data from 38 patients admitted to the NCCU after severe TBI, managed with optimal cerebral perfusion pressure (CPPopt)-guided therapy, calculated using pressure reactivity index (PRx). All patients were sedated and ventilated with lung protective criteria (Peep > 5, tidal volume 6-8 ml/kg and airway pressure < 30 cmH2O). RESULTS: Daily mean CPPopt varied between a minimum of 84 mmHg and a maximum of 91 mmHg with an all period mean value of 88 mmHg. The mean value for the difference between CPP and CPPopt was -1.9 mmHg. Daily mean P/F ratio decreased and varied between 253 and 387 with an all-period mean of 294 mmHg. During the 10 days of recording data, five patients (13%) developed criteria of severe ARDS, but only two patients died due to severe ARDS (5%). PaO2/FiO2 (P/F) ratio did not correlate with CPPopt, but showed a strong correlation with tidal volume (p = 0.000) and driving pressure (p = 0.000). CONCLUSIONS: Although CPPopt-guided therapy may induce a decrease in P/F ratio over time during the first 10 days, we could not find an association with worst outcome, which may be influenced by lung protective ventilation strategies and preservation of cerebral autoregulation.