A comprehensive and critical review of the unstandardized Folin-Ciocalteu assay to determine the total content of polyphenols: The conundrum of the experimental factors and method validation.

The Folin-Ciocalteu method can be considered to be the most widely used in laboratories around the world, to quantify the total polyphenols content. Many different variations found in this assay have been reported in the scientific literature. In this review, the full experimental conditions influencing the Folin-Ciocalteu assay have been comparatively assessed and discussed. Furthermore, few studies relating to the method validation have been evaluated according to the results of selectivity, linearity, precision, trueness, limit of determination, limit of quantification and robustness. In general, the results derived from the reviewed literature are widely variable according to both, the experimental factors selected and the performance parameters reported, making difficult the comparison of the overall results published.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey.

Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.

Turning an invasive alien species into a valuable biomass: Anaerobic digestion of Rugulopteryx okamurae after thermal and new developed low-cost mechanical pretreatments.

The invasive alien seaweed Rugulopteryx okamurae (R.o.) has spread quickly through the Mediterranean Sea causing an unprecedented ecological impact. A solution integrated into a circular economy model is needed in order to curb the negative effects of its presence. Anaerobic digestion (AD) is proposed as a feasible process able to transform biomass into renewable energy. Nevertheless, in order to improve the methane yield and surpass the drawbacks associated with AD processes, this research proposes a thermal pretreatment and a new developed method where the macroalgae is mechanically pretreated with zeolite. Chemical and microstructure characterization of the algal biomass after pretreatments involved scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The highest methane yields of 240 (28) and 250 (20) NLCH4 kg-1 VSadded were obtained with the new mechanical pretreatment and the thermal pretreatment at 120 °C for 45 min without zeolite, achieving a 35 % improvement against the non-pretreated algae. A direct relationship between the crystallinity index of the samples and methane production was observed. The experimental data of methane production versus time were found to be in accordance with both first-order kinetic and Transference Function mathematical models.

Coupling of Fused Deposition Modeling and Inkjet Printing to Produce Drug Loaded 3D Printed Tablets.

In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.

Learning Low-Dimensional Semantics for Music and Language via Multi-Subject fMRI.

Embodied Cognition (EC) states that semantics is encoded in the brain as firing patterns of neural circuits, which are learned according to the statistical structure of human multimodal experience. However, each human brain is idiosyncratically biased, according to its subjective experience, making this biological semantic machinery noisy with respect to semantics inherent to media, such as music and language. We propose to represent media semantics using low-dimensional vector embeddings by jointly modeling the functional Magnetic Resonance Imaging (fMRI) activity of several brains via Generalized Canonical Correlation Analysis (GCCA). We evaluate the semantic richness of the resulting latent space in appropriate semantic classification tasks: music genres and language topics. We show that the resulting unsupervised representations outperform the original high-dimensional fMRI voxel spaces in these downstream tasks while being more computationally efficient. Furthermore, we show that joint modeling of several subjects increases the semantic richness of the learned latent vector spaces as the number of subjects increases. Quantitative results and corresponding statistical significance testing demonstrate the instantiation of music and language semantics in the brain, thereby providing further evidence for multimodal embodied cognition as well as a method for extraction of media semantics from multi-subject brain dynamics.

Aplicações da manufatura aditiva em oftalmologia / Applications of additive manufacturing in ophthalmology

RESUMO A manufatura aditiva, mais popularmente conhecida como impressão tridimensional, baseia-se no desenvolvimento de um objeto com a ajuda de um software de desenho assistido por computador seguido de sua impressão por meio da deposição de uma matéria-prima, camada por camada, para a construção do produto desejado. Existem vários tipos de técnicas de impressão tridimensional, e o tipo de processo de impressão escolhido depende da aplicação específica do objeto a ser desenvolvido, dos materiais a serem utilizados e da resolução necessária à impressão do produto final. A impressão tridimensional abriu perspectivas na pesquisa e revolucionou o campo das ciências da saúde, com a possibilidade de criação e de desenvolvimento de produtos personalizados de maneira rápida, econômica e de forma mais centralizada do que no processo de manufatura tradicional. As tecnologias de manufatura aditiva remodelaram os diagnósticos médicos; as medidas preventivas e pré-operatórias; o tratamento e a reabilitação, assim como os processos de engenharia de tecidos nos últimos anos. Na oftalmologia, as aplicações da impressão tridimensional são extensas. Modelos anatômicos para aplicação na área da educação e planejamentos cirúrgicos, desenvolvimento de implantes, lentes, equipamentos para diagnósticos, novas aplicações terapêuticas e desenvolvimento de tecidos oculares já estão em desenvolvimento. Por possuir um campo amplo e ser alvo de pesquisa constante, a área oftalmológica permite que a manufatura aditiva ainda seja amplamente utilizada a favor dos médicos e dos pacientes.

ABSTRACT Additive manufacturing, more popularly known as three-dimensional (3D) printing, is based on the development of an object with the help of computer-aided design software followed by its printing through the deposition of a material, layer by layer, to create the desired product. There are several types of 3D printing techniques and the type of printing process chosen depends on the specific application of the object to be developed, the materials to be used, and the resolution required to print the final product. 3D printing has brought new perspectives to research and revolutionized the field of health sciences, with the possibility of creating and developing customized products in a faster, more economical, and more centralized way than in the traditional manufacturing process. Additive manufacturing technologies have reformulated medical diagnostics, preventive, preoperative, treatment, and rehabilitation, as well as tissue engineering processes in recent years. In ophthalmology, the applications of 3D printing are extensive. Anatomical models for application in education and surgical planning, development of implants, lenses, diagnostic equipment, new therapeutic applications, and development of ocular tissues (3D bioprinting) are already under development. As it has a wide field and is the subject of constant research, the ophthalmic area allows additive manufacturing to still be widely used in favor of doctors and patients.

Antibody response induced by the boost overdose during COVID-19 heterologous prime-boost vaccination strategy.

BACKGROUND: Measurement of anti-SARS-CoV-2 RBD Ig G antibody response is very important to define the dynamics of immunization in vaccine COVID-19 recipients. MATERIALS AND METHODS: Sera from four BNT162b2 vaccine recipients who erroneously received vaccine overdose were analyzed at different time-points. RESULTS: At 6 days the serum increase of antibodies was analogous for the three SARS-CoV-2 naïve recipients. At 14 days the antibody level increased and reached a peak, though showing a different pattern among the three recipients. At 21 days the serum antibody level started to decrease from its maximum value. The data for the previously infected recipient were in agreement with values found in COVID-19 positive receivers. Thus, the prime-dose of vaccine was enough to elicit a significant antibody response. CONCLUSIONS: In spite of the overdosage, this study confirms the efficiency of the BNT162b vaccine in eliciting a sustained antibody response as heterologous boost-vaccine in previously Oxford/AstraZeneca vaccinated recipients, as well as, prime-vaccine in COVID-19 infected receivers. Importantly, the humoral immune response of recipients was not proportional to the vaccine overdose. Nonetheless, we cannot portray a univocal effect of vaccine overdose concerning anti-SARS-CoV-2 antibody response because the values found were highly heterogeneous.

Magnetic resonance imaging and Ménière's disease-unavoidable alliance.

Ménière's disease (MD) is a clinical syndrome characterized by recurrent episodes of spontaneous vertigo, unilateral fluctuating sensorineural hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops is recognized as the pathophysiological substrate of the disease, having been demonstrated in anatomical pathological studies and more recently by magnetic resonance imaging (MRI). The current criteria of the disease, however, remain symptom based and do not include the demonstration of endolymphatic hydrops. The authors review MRI techniques and diagnostic criteria of endolymphatic hydrops and the role of MRI in MD is discussed.

Orodispersible Films for Compounding Pharmacies.

Orodispersible film can be defined as a solid pharmaceutical form intended for the delivery and rapid local or systemic release of active ingredients, consisting of a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity (oral, palatal, gingival, lingual, or sublingual), without the need for water administration or mastication. Due to its outstanding importance in cases of emergency, practicality of use by patients in transit, and high adherence, orodispersible film has evolved in popularity and success among consumers. It is a promising dosage form for compounding pharmacies, as simpler technologies are being developed to make the compound process easier and faster for the pharmacist. This article aims to explore some of the basics on orodispersible film and the main possible preparations to be developed in compounding pharmacies worldwide.

Technological Device for Manufacturing Transdermal Films: Possible Applications to the Individualized Treatment for Erectile Dysfunction.

Pharmacological advances in erectile dysfunction (ED) treatment have aroused growing interest among health professionals towards sexual dysfunction, generating an increasing demand for dosage forms and drug delivery systems, including tadalafil. This study aimed to develop a device to generate patches that would enable drug dosage individualization and transdermal administration. To create such a mechanical device, technical drawings were made using the CAD software. A functional prototype was built, and a pharmaceutical formulation containing tadalafil (10 mg cm-2) was prepared. An analytical method (HPLC) was developed and validated. The average weight of adhesives (n = 10) was 241.01 mg; the content uniformity for preparations in unit doses (n = 10) was 108.93%, and a CV <2% for intraadhesive tadalafil content (n = 40) was observed. The ex vivo permeation of patches containing tadalafil was determined in Franz cells (n = 6), equipped with human skin and kept for 12 h in contact with the patch, by using the tape stripping method. The optimized method showed acceptable confidence limits within the range recommended by regulatory agencies, being validated for use in this ex vivo permeation study. Tadalafil could permeate to the viable epidermis and dermis (5.7%). The created device produced homogeneous patches of tadalafil, showing such technological innovation as to be feasible in individualized therapy for the treatment of ED.

Towards a standardization of biomethane potential tests.

Production of biogas from different organic materials is a most interesting source of renewable energy. The biomethane potential (BMP) of these materials has to be determined to get insight in design parameters for anaerobic digesters. Although several norms and guidelines for BMP tests exist, inter-laboratory tests regularly show high variability of BMPs for the same substrate. A workshop was held in June 2015, in Leysin, Switzerland, with over 40 attendees from 30 laboratories around the world, to agree on common solutions to the conundrum of inconsistent BMP test results. This paper presents the consensus of the intense roundtable discussions and cross-comparison of methodologies used in respective laboratories. Compulsory elements for the validation of BMP results were defined. They include the minimal number of replicates, the request to carry out blank and positive control assays, a criterion for the test duration, details on BMP calculation, and last but not least criteria for rejection of the BMP tests. Finally, recommendations on items that strongly influence the outcome of BMP tests such as inoculum characteristics, substrate preparation, test setup, and data analysis are presented to increase the probability of obtaining validated and reproducible results.

Harmonization of the quantitative determination of volatile fatty acids profile in aqueous matrix samples by direct injection using gas chromatography and high-performance liquid chromatography techniques: Multi-laboratory validation study.

The performance parameters of volatile fatty acids (VFAs) measurements were assessed for the first time by a multi-laboratory validation study among 13 laboratories. Two chromatographic techniques (GC and HPLC) and two quantification methods such as external and internal standard (ESTD/ISTD) were combined in three different methodologies GC/ESTD, HPLC/ESTD and GC/ISTD. Linearity evaluation of the calibration functions in a wide concentration range (10-1000mg/L) was carried out using different statistical parameters for the goodness of fit. Both chromatographic techniques were considered similarly accurate. The use of GC/ISTD, despite showing similar analytical performance to the other methodologies, can be considered useful for the harmonization of VFAs analytical methodology taking into account the normalization of slope values used for the calculation of VFAs concentrations. Acceptance criteria for VFAs performance parameters of the multi-laboratory validation study should be established as follows: (1) instrument precision (RSDINST≤1.5%); (2) linearity (R(2)≥0.998; RSDSENSITIVITY≤4%; REMAX≤8%; REAVER≤ 3%); (3) precision (RSD≤1.5%); (4) trueness (recovery of 97-103%); (5) LOD (≤3mg/L); and (6) LOQ (10mg/L).

Performance and kinetic evaluation of the semi-continuous anaerobic digestion of sunflower oil cake pretreated with ultrasound.

A study of the semi-continuous anaerobic digestion of sunflower oil cake previously sonicated (at a specific energy of 24,000 kJ/kg TS, constant sonication frequency of 20 kHz and ultrasonic power of 120 W) was carried out in laboratory-scale completely stirred tank reactors at mesophilic temperature (35°C). Two anaerobic inocula were used: a mixture of flocculant biomass (I) from a full-scale anaerobic reactor treating waste activated sludge and a granular inoculum (II) from an industrial UASB reactor treating brewery wastewater. Soluble COD (CODs) removal efficiencies ranged between 67.7% and 70.1% and between 61.3% and 67.7% at hydraulic retention times (HRTs) of between 24-10 days for inoculum I and 24-8 days for inoculum II. However, for HRTs lower than 8 days and 6.7 days, equivalent to organic loading rates (OLRs) higher than 2.62 and 3.15 g COD/(L·d), respectively, a sudden decrease in the CODs removal efficiency was observed in both cases. In any case, inoculum II allowed for a more stable and efficient operation for a wider range of both OLRs and HRTs, permitting an appropriate and reliable operation for OLRs as high as 3.15 g COD/(L·d) and HRTs as low as 6.7 days. The methane production rates achieved with inoculum II were always higher than those reached with inoculum I. The overall methane yield obtained with inoculum II was 13% higher than that achieved with inoculum I. In addition, this value was 1.9 times higher than the methane yield obtained with untreated (non-sonicated) SuOC. A second-order kinetic model was found to be adequate to fit the experimental results obtained for the two inocula used. The kinetic constant obtained with inoculum I was 3.5 times higher than that achieved with inoculum II.

Effect of hydrothermal pretreatment of sunflower oil cake on biomethane potential focusing on fibre composition.

The aim of this study was to elucidate the effect of hydrothermal pretreatment at 25, 100, 150 and 200°C on fibre composition and the biomethane potential of sunflower oil cake (SuOC). An increase in pretreatment temperature from 25 to 200°C caused a decrease in hemicellulose content in the solid pretreated fraction from 13 to 6% while the lignin content increased by 16%. Soluble compounds also increased with temperature. Digestion of solid fractions from pretreatments at 25, 100, 150 and 200°C in batch assays at 35±1°C resulted in methane yields of 114±9, 105±7, 82±7 and 53±8mL CH(4) g(-1)COD(added), respectively. The corresponding methane yields for the liquid fractions were 276±6, 310±4, 220±15 and 247±10mL CH(4) g(-1)COD(added), respectively. Therefore the overall methane yield was highest for SuOC pretreated at 100°C; however, this value was only 6.5% higher than that achieved after pretreatment at 25°C.

Treatment of screened dairy manure by upflow anaerobic fixed bed reactors packed with waste tyre rubber and a combination of waste tyre rubber and zeolite: effect of the hydraulic retention time.

Two laboratory-scale anaerobic fixed bed reactors were evaluated while treating dairy manure at upflow mode and semicontinuous feeding. One reactor was packed with a combination of waste tyre rubber and zeolite (R1) while the other had only waste tyre rubber as a microorganism immobilization support (R2). Effluent quality improved when the hydraulic retention time (HRT) increased from 1.0 to 5.5 days. Higher COD, BOD5, total and volatile solids removal efficiencies were always achieved in the reactor R1. No clogging was observed during the operation period. Methane yield was also a function of the HRT and of the type of support used, and was 12.5% and 40% higher in reactor R1 than in R2 for HRTs of 5.5 and 1.0 days, respectively. The results obtained demonstrated that this type of reactor is capable of operating with dairy manure at a HRT 5 times lower than that used in a conventional reactor.

Anaerobic digestion of wastewater derived from the pressing of orange peel generated in orange juice production.

A study of the anaerobic digestion of wastewater from the pressing of orange peel generated in orange juice production was carried out in a laboratory-scale completely stirred tank reactor at mesophilic temperature (37 degrees C). Prior to anaerobic treatment the raw wastewater was subjected to physicochemical treatment using aluminum sulfate as a flocculant and to pH reduction using a solution of sulfuric acid. The reactor was batch fed at COD loads of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 g of COD. The process was very stable for all of the loads studied, with mean pH and alkalinity values of 7.5 and 3220 mg of CaCO3/L, respectively. The anaerobic digestion of this substrate was found to follow a first-order kinetic model, from which the specific rate constants for methane production, K(G), were determined. The K(G) values decreased considerably from 0.0672 to 0.0078 L/(g h) when the COD load increased from 1.5 to 5.0 g of COD, indicating an inhibition phenomenon in the system studied. The proposed model predicted the behavior of the reactor very accurately, showing deviations of <5% between the experimental and theoretical values of methane production. The methane yield coefficient was found to be 295 mL of CH4 STP/g of COD removed, whereas the mean biodegradability of the substrate (TOC) was 88.2%. A first-order kinetic model for substrate (TOC) consumption allowed determination of the specific rate constants for substrate uptake, K(C), which also decreased with increasing loading, confirming the above-mentioned inhibition process. Finally, the evolution of the individual volatile fatty acid concentrations (acetic, C2; propionic, C3; butyric, C4; isobutyric, iC4; valeric, C5; isovaleric, iC5; and caproic, C6) with digestion time for all loads used was also studied. The main acids generated were acetic and propionic for all loads studied, facilitating the conversion into methane.

Kinetics for substrate utilization and methane production during the mesophilic anaerobic digestion of two phases olive pomace (TPOP).

A kinetic study of the anaerobic digestion process of two phases olive pomace (TPOP) was carried out in a laboratory-scale completely stirred tank reactor at mesophilic temperature (35 degrees C). The reactor was operated at influent substrate concentrations of 34.5 (substrate I), 81.1 (substrate II), 113.1 (substrate III), and 150.3 g COD/L (substrate IV). The hydraulic retention times (HRT) ranged between 8.3 and 40.0 days for the most diluted substrate (I) and between 10 and 50 days for the other three influent substrate concentrations used (substrates II-IV). The results obtained demonstrated that the rates of substrate uptake and methane production were correlated with the concentration of biodegradable total chemical oxygen demand (COD), through equations of the Michaelis-Menten type. A mass (COD) balance around the reactor allowed the methane yield coefficient and cell maintenance coefficient to be obtained, which gave values of 0.25 L CH(4)/g COD(t) and 0.25 days(-1), respectively. The first one was coincident to that obtained through experimental data of methane production and substrate consumption. The kinetic equations obtained and the proposed mass balance were used to simulate the anaerobic digestion process of TPOP and to obtain the theoretical COD of the reactor and methane production rates. The small deviations obtained (equal or lower than 10%) between the values calculated through the model and experimental ones suggest that the proposed model predicts the behavior of the reactor very accurately.

Kinetic analysis of the psychrophilic anaerobic digestion of wastewater derived from the production of proteins from extracted sunflower flour.

A kinetic analysis of the anaerobic digestion process of wastewater derived from the production of protein isolates from extracted sunflower flour was carried out. The digestion was conducted in a laboratory-scale fluidized bed reactor with saponite (magnesium silicate) as support for the mediating bacteria at psychrophilic temperature (15-19 degrees C). Soluble chemical oxygen demand (COD(s)) removal efficiencies in the range of 95.9-69.0% were achieved in the reactor at organic loading rates (OLR) of between 0.57 and 2.49 g total COD (COD(t))/L d, hydraulic retention times (HRT) of between 20.0 and 4.5 days, and average feed total COD concentration of 11.3 g/L. The yield coefficient of methane production was 0.32 L of methane (at STP) per gram of COD(t) removed. The total volatile fatty acid (TVFA) levels and the TVFA/alkalinity ratio were lower than the suggested limits for digester failure for OLR and HRT up to 2.26 g COD(t)/L d and 5.0 days, respectively. The specific rate of substrate uptake, r (g COD(s)/g VSS d), correlated with the concentration of biodegradable substrate, S (g COD(s)/L), through an equation of the Michaelis-Menten type. The maximum substrate utilization rate, k, and the Michaelis constant, K(s)(), were found to be 0.125 g COD(s)/g VSS d and 124 mg COD(s)/L, respectively. This proposed model predicted the behavior of the reactor very accurately showing deviations lower than 10% between the experimental and theoretical values of substrate uptake rates. A mass (COD(t)) balance around the reactor allowed the COD equivalent of methane volume (W(CH)4) to be obtained, which gave a value of 2.89 g COD(t)/L CH(4), which was virtually coincident with the theoretical value of 2.86 g COD(t)/L CH(4).