Is it advantageous to use quality by design (QbD) to develop nanoparticle-based dosage forms for parenteral drug administration?

Parenteral administration is one of the most commonly used drug delivery routes for nanoparticle-based dosage forms, such as lipid-based and polymeric nanoparticles. For the treatment of various diseases, parenteral administration include intravenous, subcutaneous, and intramuscular route. In drug development phase, multiparameter strategy with a focus on drug physicochemical properties and the specificity of the administration route is required. Nanoparticle properties in terms of size and targeted delivery, among others, are able to surpass many drawbacks of conventional dosage forms, but these unique properties can be a bottleneck for approval by regulatory authorities. Quality by Design (QbD) approach has been widely utilized in development of parenteral nanoparticle-based dosage forms. It fosters knowledge of product and process quality by involving sound scientific data and risk assessment strategies. A full and comprehensive investigation into the state of implementation and applications of the QbD approach in these complex drug products can highlight the gaps and challenges. In this review, the analysis of critical attributes and Design of Experiment (DoE) approach in different nanoparticulate systems, together with the proper utilization of Process Analytical Technology (PAT) applications are described. The essential of QbD approach for the design and development of nanoparticle-based dosage forms for delivery via parenteral routes is discussed thoroughly.

Phytotoxic and cytogenotoxic assessment of glyphosate on Lactuca sativa L / Avaliação fitotóxica e citogenotóxica do glifosato em Lactuca sativa L

The active ingredient glyphosate is the most commercialized herbicide on the world market due to its capability in eliminating weeds. However, it can harm the development of non-target organisms and threaten environmental quality. This study analyzed the effects of potentially toxic concentrations of glyphosate on germination, growth, cell cycle and genomic stability of Lactuca sativa L., and identified the most sensitive variables for assessing the toxicity of this herbicide to this biomonitor. Seeds of L. sativa were germinated in Petri dishes containing a sheet of filter paper moistened with 5 mL of a concentration of glyphosate (1.34, 3.35, 6.70, 10.05, 13.40 mg L-1). Controls consisted of distilled water (negative) and 3 mg L-1 CuSO4 (positive). Macroscopic and microscopic variables were analyzed. The germination of L. sativa was not affected by the concentrations of glyphosate. Root length and shoot height of the plants and the mitotic index decreased from the lowest concentration tested on. The chromosomal anomaly index and frequency of micronuclei increased by 3.2 and 22 times, respectively, with the presence of the lowest concentration of glyphosate compared to the negative control. The observed phytotoxic and cytogenotoxic effects demonstrate the negative influence that glyphosate has on the development of L. sativa. Root length and microscopic variables showed the highest sensitivity. This study warns of the possible harmful effects that glyphosate can have on non-target organisms and suggests greater control over the use of this herbicide to mitigate its environmental impact.

O ingrediente ativo glifosato é o herbicida mais comercializado do mercado mundial, pela sua capacidade de eliminar as plantas daninhas. No entanto, ele pode prejudicar o desenvolvimento dos organismos não-alvo e ameaçar a qualidade do ambiente. O estudo teve como objetivo analisar os efeitos de concentrações potencialmente tóxicas de glifosato sobre a germinação, o crescimento, o ciclo celular e a estabilidade genômica de Lactuca sativa L., e identificar as variáveis mais sensíveis para avaliar a toxicidade deste herbicida ao biomonitor. Sementes de L. sativa foram germinadas em placas de Petri contendo uma folha de papel-filtro umedecida com 5 mL das concentrações de glifosato (1,34, 3,35, 6,70, 10,05, 13,40 mg L-1). Os controles consistiram em água destilada (negativo) e 3 mg L-1 de CuSO4 (positivo). Variáveis macroscópicas e microscópicas foram analisadas. A germinação de L. sativa não foi afetada pelas concentrações de glifosato. O comprimento da raiz e a altura da parte aérea das plantas e o índice mitótico reduziram desde a menor concentração testada. O índice de anomalias cromossômicas e a frequência de micronúcleos aumentaram, respectivamente, 3,2 e 22 vezes na presença da menor concentração de glifosato em comparação ao controle negativo. Os efeitos fitotóxicos e citogenotóxicos observados demonstram a interferência negativa do herbicida no desenvolvimento de L. sativa. O comprimento da raiz e as variáveis microscópicas foram as que apresentaram maior sensibilidade. Este estudo alerta sobre os possíveis efeitos prejudiciais que o glifosato pode provocar nos organismos não-alvo, sugerindo um maior controle quanto à utilização deste herbicida, a fim de mitigar o seu impacto ambiental.

Phytotoxic and cytogenotoxic assessment of glyphosate on Lactuca sativa L

Abstract The active ingredient glyphosate is the most commercialized herbicide on the world market due to its capability in eliminating weeds. However, it can harm the development of non-target organisms and threaten environmental quality. This study analyzed the effects of potentially toxic concentrations of glyphosate on germination, growth, cell cycle and genomic stability of Lactuca sativa L., and identified the most sensitive variables for assessing the toxicity of this herbicide to this biomonitor. Seeds of L. sativa were germinated in Petri dishes containing a sheet of filter paper moistened with 5 mL of a concentration of glyphosate (1.34, 3.35, 6.70, 10.05, 13.40 mg L-1). Controls consisted of distilled water (negative) and 3 mg L-1 CuSO4 (positive). Macroscopic and microscopic variables were analyzed. The germination of L. sativa was not affected by the concentrations of glyphosate. Root length and shoot height of the plants and the mitotic index decreased from the lowest concentration tested on. The chromosomal anomaly index and frequency of micronuclei increased by 3.2 and 22 times, respectively, with the presence of the lowest concentration of glyphosate compared to the negative control. The observed phytotoxic and cytogenotoxic effects demonstrate the negative influence that glyphosate has on the development of L. sativa. Root length and microscopic variables showed the highest sensitivity. This study warns of the possible harmful effects that glyphosate can have on non-target organisms and suggests greater control over the use of this herbicide to mitigate its environmental impact.

Resumo O ingrediente ativo glifosato é o herbicida mais comercializado do mercado mundial, pela sua capacidade de eliminar as plantas daninhas. No entanto, ele pode prejudicar o desenvolvimento dos organismos não-alvo e ameaçar a qualidade do ambiente. O estudo teve como objetivo analisar os efeitos de concentrações potencialmente tóxicas de glifosato sobre a germinação, o crescimento, o ciclo celular e a estabilidade genômica de Lactuca sativa L., e identificar as variáveis mais sensíveis para avaliar a toxicidade deste herbicida ao biomonitor. Sementes de L. sativa foram germinadas em placas de Petri contendo uma folha de papel-filtro umedecida com 5 mL das concentrações de glifosato (1,34, 3,35, 6,70, 10,05, 13,40 mg L-1). Os controles consistiram em água destilada (negativo) e 3 mg L-1 de CuSO4 (positivo). Variáveis macroscópicas e microscópicas foram analisadas. A germinação de L. sativa não foi afetada pelas concentrações de glifosato. O comprimento da raiz e a altura da parte aérea das plantas e o índice mitótico reduziram desde a menor concentração testada. O índice de anomalias cromossômicas e a frequência de micronúcleos aumentaram, respectivamente, 3,2 e 22 vezes na presença da menor concentração de glifosato em comparação ao controle negativo. Os efeitos fitotóxicos e citogenotóxicos observados demonstram a interferência negativa do herbicida no desenvolvimento de L. sativa. O comprimento da raiz e as variáveis microscópicas foram as que apresentaram maior sensibilidade. Este estudo alerta sobre os possíveis efeitos prejudiciais que o glifosato pode provocar nos organismos não-alvo, sugerindo um maior controle quanto à utilização deste herbicida, a fim de mitigar o seu impacto ambiental.

Supplementation of sulfate polysaccharides in the seminal cooling medium of common curimata (Prochilodus brevis).

BACKGROUND: The use of sulfated polysaccharides (PS) in seminal cooling is known to improve seminal quality. OBJECTIVE: To evaluate the effect of different concentrations of PS, extracted from the macroalgae Gracilaria domigensis as a supplement to the seminal cooling medium of the reophilic fish Prochilodus brevis (common curimatã). MATERIALS AND METHODS: Five semen pools were diluted in ACP-104 (treatment T1), in BTS® (T2) and in BTS® with different concentrations of PS (0.5 [T3]; 1.0 [T4] and 1.5 [T5]). The samples were cooled for different times (0, 6, 24, 48, 72, 96 and 120 h) and after each hour they were analyzed for: morphology, membrane integrity, DNA integrity and sperm kinetics. RESULTS: There were no significant differences between the treatments containing different concentrations of sulfated polysaccharides. Regarding the different cooling times, it was possible to observe that after hour 96, there was a reduction in the parameters of sperm kinetics. For DNA integrity there was no significant difference in relation to the treatments nor in relation to the hours. For membrane integrity, a reduction was noted as of hour 96, but there was no influence of polysaccharides. For the sperm morphology, there was no statistical difference between the hours, however the BTS was better than the ACP-104. CONCLUSION: It is concluded that the use of polysaccharides in seminal cooling has no negative effect on sperm parameters and proves that seminal cooling keeps the material viable for up to 72 hours. Doi: 10.54680/fr23410110512.

Ultrasound-guided repositioning technique for partially expelled intrauterine device: descriptive feasibility study.

OBJECTIVE: To describe the feasibility of an ultrasound-guided repositioning technique for partially expelled intrauterine devices (IUDs) without use of sedation. METHODS: This was a descriptive feasibility study of patients with a partially expelled IUD managed in our outpatient clinic from January 2016 to February 2020. The partially expelled IUDs (vertical arm extending partially or entirely through the cervical canal) were repositioned at the uterine fundus using Hartmann alligator forceps under ultrasound guidance. Paracervical or intracervical anesthesia and prophylactic antibiotics were not used. Data related to the procedure and 6-month follow-up were extracted from patient medical records. The primary outcome was the success rate of the repositioning procedure, defined as ultrasound confirmation of the entire IUD located above the internal os. Secondary outcomes included the retention and expulsion rates of the repositioned IUD at 6 months after the procedure and description of complications. RESULTS: We included data from 55 women with a partially expelled IUD (35 levonorgestrel IUDs and 20 copper IUDs) referred for repositioning. Ultrasound-guided repositioning of the IUD was successful in 51 (92.7%) cases, while the procedure was not completed in four patients due to pain. Of the 55 procedures, 48 (87.3%) were performed by obstetrics and gynecology trainees under the supervision of a senior specialist. Among the 51 successfully repositioned IUDs, nine (17.6%) were expelled within 6 months after the procedure and six patients were lost to follow-up. No uterine perforation or infection-related complications occurred within 6 months of the procedure. CONCLUSION: The ultrasound-guided repositioning technique appears to be a safe and feasible approach for partially expelled IUDs. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Phytotoxic and cytogenotoxic assessment of glyphosate on Lactuca sativa L.

The active ingredient glyphosate is the most commercialized herbicide on the world market due to its capability in eliminating weeds. However, it can harm the development of non-target organisms and threaten environmental quality. This study analyzed the effects of potentially toxic concentrations of glyphosate on germination, growth, cell cycle and genomic stability of Lactuca sativa L., and identified the most sensitive variables for assessing the toxicity of this herbicide to this biomonitor. Seeds of L. sativa were germinated in Petri dishes containing a sheet of filter paper moistened with 5 mL of a concentration of glyphosate (1.34, 3.35, 6.70, 10.05, 13.40 mg L-1). Controls consisted of distilled water (negative) and 3 mg L-1 CuSO4 (positive). Macroscopic and microscopic variables were analyzed. The germination of L. sativa was not affected by the concentrations of glyphosate. Root length and shoot height of the plants and the mitotic index decreased from the lowest concentration tested on. The chromosomal anomaly index and frequency of micronuclei increased by 3.2 and 22 times, respectively, with the presence of the lowest concentration of glyphosate compared to the negative control. The observed phytotoxic and cytogenotoxic effects demonstrate the negative influence that glyphosate has on the development of L. sativa. Root length and microscopic variables showed the highest sensitivity. This study warns of the possible harmful effects that glyphosate can have on non-target organisms and suggests greater control over the use of this herbicide to mitigate its environmental impact.

Effects of grape pomace supplementation on the diet of lactating ewes as compared to vitamin E on the meat shelf life of suckling lambs.

Forty-eight Churra ewes and their suckling lambs were assigned to four dietary treatments: control (CTRL), VIT-E (500 mg kg-1 TMR vitamin E), GP-5 (5% grape pomace) and GP-10 (10% grape pomace). After slaughter (11.5 kg live weight), longissimus muscle of lambs was sliced, packaged under modified atmosphere (80,20%/O 2:CO 2) and stored in retail conditions. At each sampling point (0, 3, 7, 10, 14 days), microbiological, physicochemical and sensory characteristics were analysed. Vitamin E and GP-5 were found to be effective (p < 0.05) at preventing enterobacteria growth as of day 10. After day 10, vitamin E and grape pomace in the ewe's supplementation reduced metmyoglobin (p < 0.05) lipid oxidation (p < 0.05) and sensory spoilage throughout the storage period. An effect of the grape pomace dosage was observed, with the supplementation at 5% being more effective. Therefore, we can conclude that grape pomace was just as effective as vitamin E in preventing spoilage during retail storage.

Activation of C-C motif chemokine receptor 2 modulates testicular macrophages number, steroidogenesis, and spermatogenesis progression.

The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C-C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population's functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood-testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.

The identification of the Rosa S-locus and implications on the evolution of the Rosaceae gametophytic self-incompatibility systems.

In Rosaceae species, two gametophytic self-incompatibility (GSI) mechanisms are described, the Prunus self-recognition system and the Maleae (Malus/Pyrus/Sorbus) non-self- recognition system. In both systems the pistil component is a S-RNase gene, but from two distinct phylogenetic lineages. The pollen component, always a F-box gene(s), in the case of Prunus is a single gene, and in Maleae there are multiple genes. Previously, the Rosa S-locus was mapped on chromosome 3, and three putative S-RNase genes were identified in the R. chinensis 'Old Blush' genome. Here, we show that these genes do not belong to the S-locus region. Using R. chinensis and R. multiflora genomes and a phylogenetic approach, we identified the S-RNase gene, that belongs to the Prunus S-lineage. Expression patterns support this gene as being the S-pistil. This gene is here also identified in R. moschata, R. arvensis, and R. minutifolia low coverage genomes, allowing the identification of positively selected amino acid sites, and thus, further supporting this gene as the S-RNase. Furthermore, genotype-phenotype association experiments also support this gene as the S-RNase. For the S-pollen GSI component we find evidence for multiple F-box genes, that show the expected expression pattern, and evidence for diversifying selection at the F-box genes within an S-haplotype. Thus, Rosa has a non-self-recognition system, like in Maleae species, despite the S-pistil gene belonging to the Prunus S-RNase lineage. These findings are discussed in the context of the Rosaceae GSI evolution. Knowledge on the Rosa S-locus has practical implications since genes controlling floral and other ornamental traits are in linkage disequilibrium with the S-locus.

Antimicrobial activity and toxicity of glass ionomer cement containing an essential oil.

The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.

Estruturas fetais e suas correlações com a predição do dia antes do parto em raças de cães miniaturas / Fetal structures and their correlations with a prediction of the parturition date in the miniature canine breeds

Avaliou-se a correlação entre estruturas fetais e extrafetais com a predição do dia antes do parto (DAP) em raças de cães miniaturas. Para isso, realizou-se um experimento, utilizando-se 12 cadelas, com peso corporal entre 3,0kg e 5,0kg, sendo seis da raça Chihuahua, duas da raça Shih-Tzu, duas da raça Spitz Alemão e duas da raça Yorkshire. Foram mensurados, por meio da ultrassonografia, diâmetro biparietal (DBP), diâmetro torácico (DTX), diâmetro abdominal (DAB), comprimento craniocaudal (CCC), diâmetro da cavidade coriônica interna (DCI) e espessura da placenta (EP), a partir do 15º dia após a última monta. Foram estudadas as correlações simples e a significância dos coeficientes de regressão linear simples e o coeficiente de determinação (R), com nível de significância estabelecido em P<0,05. Entre os parâmetros avaliados, DBP, DTX, DAB e CCC foram os mais correlacionados com tempo gestacional, podendo ser utilizados para prever dia antes do parto em cadelas de raças miniaturas.(AU)

The correlation between fetal and extra-fetal structures with the pre-delivery prediction (DAP) in miniature dog breeds was evaluated. For this, an experiment was carried out using 12 bitches, with body weight between 3.0kg and 5.0kg, being 6 Chihuahua, 2 Shih-Tzu, 2 German Spitz and 2 Yorkshire breed. The Biparietal Diameter (BD), Thoracic Diameter (TD), Abdominal Diameter (AD), Crown-rump length (CRL), Internal Chorionic Cavity Diameter (ICD) and Placenta Thickness (PT) were measured by ultrasonography from the 15th day after the last mating. The simple correlations and significance of simple linear regression coefficients and the coefficient of determination (R) were studied, with a significance level of P<0.05. BD, T, AD and CRL were the most correlated with gestational time, and can be used to predict day before delivery in miniature breed bitches.(AU)

Bromine biogeodynamics in the NE Atlantic: A perspective from natural wetlands of western Portugal.

Bromine (Br) cycling in natural wetlands is highly complex, including abiotic/biotic processes and multiphase inorganic/organic Br-species. Wetland ecosystems receive Br primarily from the ocean, functioning as either sinks or sources of Br, with the overall imbalance largely decided by the prevailing climate. Aiming to trace the present-day transport of oceanogenic Br (i.e., derived from salt-water spray-droplets) and its uptake and storage in brackish and freshwater wetlands, we surveyed waters, autochthonous plants, and soils/sediments from coastal marshes and mountain peatlands in the westernmost fringe of northern Portugal. The calculated enrichment factors of bromide (Br-) relative to chloride in rainfall (EFsea = 16.8-75.3), rivers (EFsea = 1.3-13.9) and wetland waters, superficial (EFsea = 5.8-13.1) and interstitial (EFsea = 2.1-8.9), increased towards the inland highlands. We hypothesized that these values derived mostly from a known Br autocatalytic (heterogeneous) chemical cycle, starting at the seawater-aqueous interface and progressing in altitude. Br-bearing air masses are carried far from the Atlantic Ocean by moist westerlies, with Br- rainout from the atmosphere supplying the neighbouring mountain peatlands. Average [Br] in sampled wetland soils/sediments (111-253 mg/kg) agreed with values from other coastal regions, and they were directly correlated with the abundance of organic matter, varying irrespective the [Br-] of interstitial waters (129 µg/L-79 mg/L). According to the computed bioconcentration factors, the aqueous component was the major source of Br for all plant species investigated (BFplant/water = 2.1-508.0), as described elsewhere. However, Br contents in plants (14-173 mg/kg) evidenced interspecific differences, also suggesting a divergence from the acknowledged halophytic-glycophytic "model". As plants are recognized producers of Br volatile molecules (e.g., methyl bromide, CH3Br), we interpreted translocation factors less than one in vascular species as explanatory of phytovolatilization rather than restriction of Br- upward movement in plants. Further investigation is needed, since considerable intrinsic plant variations in CH3Br emissions are mentioned in the literature.

Antimicrobial activity and toxicity of glass ionomer cement containing an essential oil

The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.

In vitro activity of antimicrobial-impregnated catheters against biofilms formed by KPC-producing Klebsiella pneumoniae.

AIM: To evaluate the activity and effectiveness of impregnated central venous catheters (CVC) against Klebsiella pneumoniae biofilms. METHODS AND RESULTS: The antimicrobial activity and durability of impregnated-CVCs were evaluated over time and the size of zones of inhibition (ZI) was measured. Biofilm formation was observed by quantitative culture and also by scanning electron microscopy. The catheters impregnated with chlorhexidine/silver sulfadiazine (CHX/SS) reduced bacteria counts by 0·3 log and were most effective (P < 0·01) against Klebsiella pneumoniae biofilms N-acetylcysteine/levofloxacin (NAC/LEV) catheters. It was observed that the catheter impregnated with NAC/LEV had initially the largest average ZI size being statistically significant (P < 0·01). The NAC/LEV combination remained active until day 30, whereas the combination of CHX/SS was completely inactivated from day 15 on. CONCLUSIONS: The NAC/LEV combination showed greater durability on the catheters, but it was the CHX/SS combination that had the greater initial efficacy in bacterial inhibition. It was also observed that NAC/LEV-impregnated catheters do not prevent the emergence of resistant subpopulations inside the inhibition halos during antimicrobial susceptibility tests. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results highlighted that the in vitro efficacy of antimicrobial-impregnated CVCs is limited by time and that their colonization occurred earlier than expected. Our data also demonstrated that NAC/LEV remained active until day 30 of evaluation and CHX/SS combination was completely inactivated from day 15 on. Our findings suggested that implantable devices should be carefully used by medical community.

Lights4Violence: a quasi-experimental educational intervention in six European countries to promote positive relationships among adolescents.

BACKGROUND: Preventing intimate partner violence or dating violence (DV) among adolescents is a public health priority due to its magnitude and damaging short and long-term consequences for adolescent and adult health. In our study protocol, we complement prior experiences in DV prevention by promoting protective factors (or assets) against gender violence such as communication skills, empathy and problem-solving capability through "Cinema Voice", a participatory educational intervention based on adolescents' strengths to tackle DV. METHODS/DESIGN: A longitudinal quasi-experimental educational intervention addressed to boys and girls ages 13-17 years, enrolled in secondary education schools in Alicante (Spain), Rome (Italy), Cardiff (UK), Iasi (Romania), Poznan (Poland) and Matosinhos (Portugal). Both process and results evaluations will be carried out with 100-120 intervention and 120-150 control group students per city at three time periods: before, after and 6 months after the implementation of the following interventions: 1) Training seminar with teachers to promote knowledge and skills on the core issues of intervention; 2) Workshops with intervention groups, where participants produce their own digital content presenting their perspective on DV; and 3) Short film exhibitions with participants, their families, authorities and other stakeholders with the objective of share the results and engage the community. Outcome measures are self-perceived social support, machismo, sexism, tolerance towards gender violence, social problem-solving and assertiveness as well as involvement in bullying/cyberbullying. Other socio-demographic, attitudes and violence-related co-variables were also included. DISCUSSION: This study may provide relevant information about the effectiveness of educational interventions that combine a positive youth development framework with educational awareness about the importance of achieving gender equality and preventing and combating gender violence. To our knowledge, this is the first study that involves six European countries in an educational intervention to promote violence protective assets among enrolled adolescents in secondary schools. This study may provide the needed tools to replicate the experience in other contexts and other countries. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03411564 . Unique Protocol ID: 776905. Date registered: 18-01-2018.

Blocking and remanence properties of weakly and highly interactive cobalt ferrite based nanoparticles.

We compare both magnetic blocking properties and remanence curves for dilute ferrofluid and powder samples of ferrite magnetic nanoparticles. Low field DC magnetization, AC susceptibility, isothermal remanent magnetization and DC demagnetization techniques are employed to investigate the role of interparticle magnetic interactions on the superparamagnetic relaxation, the magnetic anisotropy and on the super-spin-glass state in closely packed particles. The samples used herein are 3 nm sized spinel-type nanocrystals made of a cobalt ferrite core covered by a layer of maghemite on its outermost surface and can be obtained as aqueous colloidal dispersions thanks to this core-shell strategy. They show large anisotropy attributed to an enhanced surface contribution and the blocking temperature is shifted towards higher values as interparticle distance decreases. For all investigated diluted liquids and powder samples the frequency dependency of the peak temperature is well accounted by a Vogel-Fulcher law, with the insertion of a phenomenological temperature associated to the magnitude of interparticle dipolar interactions. The fractional change of the peak temperature per decade of frequency enlights the presence of interactions between particles in dilute liquids and of a spin-glass-like state in powder samples. The remanence curves always show global demagnetizing behavior, attributed to the combination of both spin surface disorder and interparticle dipolar interactions, the former being predominant in isolated nanoparticles and the latter in powder samples. However, in the most compacted powder, exchange interaction between surface ions of different particles becomes more pronounced and promotes an additive magnetizing effect.

Clinical efficacy of new α-bisabolol mouthwashes in postoperative complications of maxillofacial surgeries: a randomized, controlled, triple-blind clinical trial.

OBJECTIVES: The present study aimed to evaluate the efficacy of α-bisabolol (BISA)-based mouthwashes in the oral hygiene of patients submitted to oral and maxillofacial surgery. MATERIALS AND METHODS: A randomized, controlled, triple-blind clinical trial was conducted with 30 patients, undergoing oral and maxillofacial surgery. Three types of mouthwashes were developed, based at 0.12% chlorhexidine, 0.5% BISA, and 0.12% chlorhexidine + 0.5% BISA. The patients were evaluated in the preoperative and postoperative period, divided into three groups according to the mouthwash to be used. In the postoperative period, the oral hygiene quality of the patients was evaluated through the simplified oral hygiene index; the healing of the wounds was evaluated observing the presence of suture dehiscence and/or infection, and the pain was established using the Visual Analogue Scale. The antiseptic effect of the mouthwashes was evaluated in vitro. RESULTS: There were no differences in the efficacy of BISA-containing mouthwashes for oral hygiene, healing, and pain, compared to chlorhexidine based at 0.12%. There were no differences in the antiseptic activity of chlorhexidine and chlorhexidine + α-bisabolol-based mouthwashes. CONCLUSION: The results indicate that BISA-based mouthwashes have clinical efficacy, in the improvement of oral hygiene and wound healing, as well as in the reduction of postoperative pain. CLINICAL RELEVANCE: Considering that BISA has analgesic, antimicrobial, and anti-inflammatory properties, it is relevant to evaluate the efficacy of BISA-based mouthwashes in the oral hygiene of patients undergoing oral and maxillofacial surgery, seeking a better postoperative recovery.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition.

AIM: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. METHODS: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. RESULTS: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. CONCLUSIONS: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.