Trunk, Mass Grasp, Knee, and Hip Muscle Performance in CrossFit Participants: Reference Values According to Participants' Sex and Limb Dominance.

Background: CrossFit is characterized by a diverse range of exercises recruiting different muscles and requiring different muscle functions. A characterization of muscular performance parameters in this population is needed. Purpose: To determine reference values for various aspects of muscular performance of muscles of the trunk, thigh, hip, and mass grasp in CrossFit participants. Also, this investigation aimed to compare the strength measures between male and female CrossFit participants, as well as between dominant and non-dominant limbs. Design: Descriptive, Cross-sectional. Setting: Laboratory. Methods: Isometric strength of trunk extensors (TE) and mass grasp was measured with handheld and Jamar dynamometer respectively. An isokinetic dynamometer was used to assess the muscle performance of the knee flexors (KF) and extensors (KE) (at 60º/s and 300º/s), and hip flexors (HF), extensors (HE), and abductors (HA) (60º/s and 240º/s ). Reference values for torque, work, power, fatigue, flexor:extensor ratio for the knee (hamstring:quadriceps - H:Q) and hip (HF:HE) joints were calculated. The torque and work values were normalized by the body mass. Mixed multivariate and univariate analyses of variance and independent t-tests were used for statistical analyses to compare between sexes and limbs. Results: Participants included 111 individuals (58 males and 53 females) with at least one year of experience in CrossFit. Normative data are provided for the outcome variables. Males had greater values of muscular performance parameters than females in most variables (p<0.05). Also, the dominant limb had greater mass grasp strength (p<0.002), greater KE power at 60º/s (p=0.015), lower H:Q ratio at 60º/s (p=0.021) and 300º/s (p=0.008), and lower KE fatigue (p=0.002). Conclusion: This study provides reference values for the trunk extensors, mass grasp, knee, and hip muscle performance in male and female CrossFit practitioners. Their muscle performance profile was characterized by few inter-limb asymmetries, and males demonstrated greater muscular performance outcomes than females, even after normalization by body mass. These reference values can be used for comparisons in research and clinical settings. Level of Evidence: 3b.

A new marker cluster anchored to the iliotibial band improves tracking of hip and thigh axial rotations.

Tracking hip and thigh axial rotation has limited accuracy due to the large soft tissue artifact. We proposed a tracking-markers cluster anchored to the prominent distal part of the iliotibial band (ITB) to improve thigh tracking. We investigated if the ITB cluster improves accuracy compared with a traditionally used thigh cluster. We also compared the hip kinematics obtained with these clusters during walking and step-down. Hip and thigh kinematics were assessed during a task of active internal-external rotation with the knee extended, in which the shank rotation is a reference due to smaller soft-tissue artifact. Errors of the hip and thigh axial rotations obtained with the thigh clusters compared to the shank cluster were computed as root-mean-square errors, which were compared by paired t-tests. The angular waveforms of this task were compared using the statistical parametric mapping (SPM). Additionally, the hip waveforms in all planes obtained with the thigh clusters were compared during walking and step-down, using Coefficients of Multiple Correlation (CMC) and SPM (α = 0.05 for all analyses). The ITB cluster errors were approximately 25 % smaller than the traditional cluster error (p < 0.001). ITB cluster errors were smaller at external rotation angles while the traditional cluster error was smaller at internal rotation angles (p < 0.001), although the clusters' waveforms were not significantly different (p ≥ 0.005). During walking and step-down, both clusters provided similar hip kinematics (CMC ≥ 0.75), but differences were observed in parts of the cycles (p ≤ 0.04). The findings suggest that the ITB cluster may be used in studies focused on hip axial rotation.

Evaluation of the nicotine metabolite ratio in smoking patients treated with varenicline and bupropion.

Background: Smoking is the leading cause of preventable death worldwide. It is responsible for several types of cancer, cardiovascular diseases, and diseases of the reproductive system, among others. Therefore, advances in research are increasingly necessary in order to make smoking cessation treatment more effective. Some studies have investigated the association of the nicotine metabolite ratio (NMR) with general characteristics and treatment outcomes. In the present study, the main aim was to evaluate the NMR in smoking patients from an Assistance Program of a tertiary cardiology hospital. Methodology: Serum samples were collected from 185 patients at T0 (while patients were still smoking and before starting pharmacological treatment). Cotinine and hydroxycotinine analytes were measured using liquid-chromatography tandem mass-spectrometry (LC-MS/MS). By looking at the relationship between hydroxycotinine and cotinine, we can obtain the NMR, with which it is possible to classify patients into slow metabolizers (NMR < 0.31), as well as normal or fast metabolizers (NMR ≥ 0.31). Results: From 185 patients, 55 were considered slow metabolizers and 130 as normal/fast. The metabolite averages were associated with the number of cigarettes smoked per day (p < 0.001 for cotinine and 0.023 hydroxycotinine). However, we were unable to analyze the association of the NMR with general and clinical characteristics of patients under smoking cessation treatment. Conclusion: We were able to evaluate the NMR, and to observe categories of metabolizers in Brazilian patients under pharmacological treatments. Thus, this study can contribute to the indication of a form of analysis, which might form part of the customization of smoking cessation treatments and, consequently, improve the success rates.

Online restricted access molecularly imprinted solid-phase extraction coupled with liquid chromatography-mass spectrometry for the selective determination of serum bile acids.

A rapid and sensitive online restricted access molecularly imprinted solid-phase extraction method coupled to a liquid chromatography-mass spectrometry (LC-MS) system for simultaneous determination of serum bile acids as well as their taurine and glycine conjugates was developed. Reversible liver damage of workers exposed to volatile organic solvents can be investigated based on the level of the analyzed molecules. A restricted access molecularly imprinted polymer coated with bovine serum albumin (RAMIP-BSA) was synthesized and used as the extraction phase. The column switching liquid chromatography system was able to exclude about 100% of the macromolecules and extract/separate nine bile acids from blood human serum samples, in a total time of 40 minutes. The developed method was validated based on the Food and Drug Administration (FDA) guidelines, being linear for all the analytes in their respective analytical ranges (coefficients of determination higher than 0.99), with limits of detection (LOD) and quantification (LOQ) ranging from 2.0 to 5.7 µg L-1 and from 10.0 to 25.0 µg L-1, respectively. Suitable results for precision (relative standard deviation ranged from 3.2 to 14.5% and 0.7 to 14.8%, respectively for intra and inter-assay) and accuracy (relative error ranged from -14.8 to 14.2%; -13.8 to 14.3%) were obtained. The validated analytical method was applied to determine bile acids in serum samples of five workers occupationally exposed to volatile organic solvent, demonstrating its applicability in the assessment of these toxicants.

Online biological sample preparation with restricted access hybrid carbon nanotubes for determination of anti-smoking drugs.

Untreated samples were injected directly into a column switching system, an online SPE technique, using an extraction column packed with restricted access hybrid carbon nanotubes (RAHCNTs), a novel type of restricted access material, in an ultra-high performance liquid chromatography, coupled to a mass spectrometer (UHPLC-MS/MS). The synthesis of used restricted access material was relatively simple, quick, and reproducible, and had a high material yield. Compared to its predecessor, which is covered with bovine serum albumin (Restricted Access Carbon Nanotubes-RACNTs), RAHCNTs have improved performance when used for the analysis of organic compounds. These molecules have a greater adsorption capacity due to the insertion of hydrophilic monomers (tetraethyl orthosilicate (TEOS), 3-(trimethoxysilyl)propyl methacrylate (MPS), glycerol dimethacrylate (GDMA), and hydroxyethyl methacrylate (HEMA)) in the external layer. In addition, the formation of the hybrid material provides greater chemical and thermal stability, supporting wide pH and temperature ranges, and high concentrations of acidic and basic solutions. It also supports high proportions of organic solvents in the medium. Another significant advantage of the material is its longer lifetime, as it can be reused for approximately 500 analytical cycles without any loss of efficiency, versus 300 for RACNTs. In the method developed to determine anti-smoking drugs (varenicline and bupropion) simultaneously, as well as nicotine and some of their metabolites in human blood serum, the RAHCNTs were capable of retaining the analytes efficiently, whereas the macromolecules were excluded (almost 100%). The method was linear for all the determined analytes (coefficients of determination higher than 0.99), with limits of detection and quantification ranging from 0.6 to 2.5 µg L-1 and from 1.0 to 5.0 µg L-1, respectively. High extraction recovery values were obtained (higher than 88%), as well as inter and intra-assay accuracy and precision results that are in accordance with values recommended by the FDA. The method is promising for therapeutic monitoring and new personalized strategies for patients under antismoking treatment, using a small sample volume (100 µL). In addition, RAHCNTs are capable of simultaneously extracting analytes with very different physical-chemical characteristics.

Multivariate Optimization of an SPME Technique for GC-MS Analysis of Urinary BTX.

Volatile organic compounds (VOCs), such as benzene, toluene and xylenes (BTX), are recognized as environmental contaminants due to their acute and chronic toxic effects, and toluene is a substance contained in products used in inhalants. In this way, methods able to determine these substances in non-invasive matrices offer great applicability for assessing acute exposure. In this study, a functionalized polymer, chloropropyltrimethoxysilane/polydimethylsiloxane, was evaluated as a potential material to be used in solid-phase microextraction for the quantification of BTX in urine by gas chromatography coupled to mass spectrometry (GC-MS). The method optimization was performed by using fractional factorial planning 2 (4-1) and the Doehlert's experiment. Desorption time and salinity were the most important factors that impact the sensitivity of the method. Spectroscopic and thermogravimetric characterization demonstrated the functionalization of the material and its thermal stability up to 390°C. This allowed it to be used for ~60 analytical cycles without loss of efficiency. The proposed method demonstrated a satisfactory analytical performance to determine the VOCs studied. The protocol agrees with the principles of green analytical chemistry since the procedure reduced the reagents consumed and wastes generated. It represents a promising tool for acute exposure assessment to BTX since urine tests demonstrated its applicability.

Molecularly Imprinted Solid Phase Extraction Aiding the Analysis of Disease Biomarkers.

Low concentrations of biomarkers as well as the complexity of biological samples make the clinical diagnoses of several diseases a challenging task. Sample preparation protocols remain a fundamental piece in the puzzle of analytical processes, and smart sorbents including molecularly imprinted polymers (MIPs) have been successfully used in this case. In this review, we depict the state of art for the rational design of MIPs to be used in solid phase extraction of disease biomarkers from biological samples. The topics are divided into (1) strategies for MIP syntheses, (2) setups for sample preparation protocols with MIPs, (3) the applications of these combined principles in the analyses of different classes of disease biomarkers, and (4) remaining challenges and future trends for the application of Molecular Imprinting Technology in sample preparation for clinical diagnosis.

Toxicological analyses: analytical method validation for prevention or diagnosis.

The need for reliable results in Toxicological Analysis is recognized and required worldwide. The analytical validation ensures that a method will provide trustworthy information about a particular sample when applied in accordance with a predefined protocol, being able to determine a specific analyte at a distinct concentration range for a well-defined purpose. The driving force for developing method validation for bioanalytical projects comes from the regulatory agencies. Thus, the approach of this work is to present theoretical and practical aspects of method validation based on the analysis objective, whether for prevention or diagnosis. Although various legislative bodies accept differing interpretations of requirements for validation, the process for applying validation criteria should be adaptable for each scientific intent or analytical purpose.

Ultrasound evaluation of schistosomiasis-related morbidity among the Xakriabá people in the state of Minas Gerais, Brazil.

OBJECTIVE: To use ultrasound to investigate the morbidity related to schistosomiasis in the Xakriabá indigenous population. MATERIALS AND METHODS: This was a field-based census study conducted in the territory of the Xakriabá people. A total of 166 individuals were invited, and 148 (≤ 77 years of age) agreed to participate. Most participants underwent abdominal ultrasound, physical examination, and stool examination. Mann-Whitney U and chi-square tests were used for comparisons. We determined risk by calculating odds ratio (OR) and performed logistic regression analysis. RESULTS: Schistosoma mansoni eggs were found in 31 (26.7%) of the 116 stool samples examined, 22 (70.9%) of the 31 being from individuals 4-16 years of age. The median count was 144 eggs/g of feces (interquartile range, 264). Of the 105 participants examined with ultrasound, 68 (64.8%) had hepatomegaly (left lobe), 6 (5.7%) had splenomegaly, and 4 (3.8%) had portal hypertension. Egg-positive stool samples were more common in those with an enlarged left lobe (OR = 3.4; 95% confidence interval (CI): 1.1-11.2; p = 0.043). Periportal fibrosis was found in 30 participants (28.6%), of whom 9 (30%) had pattern C, 10 (33.3%) had pattern D, and 11 (36.7%) had pattern Dc. Age was the only independent risk factor for fibrosis (p = 0.007). Fibrosis was up to nine-fold more common in alcohol drinkers than in nondrinkers (OR = 9.28; 95% CI: 2.60-33.06; p < 0.001). Among the 138 participants in whom the clinical form was classified, the chronic hepatic form was identified in 54 (39.1%), of whom 32 (59.2%) were under 30 years of age and one (1.8%) was hepatosplenic. CONCLUSION: Schistosomiasis in the Xakriabá population is characterized by a high frequency of egg-positive stool samples, predominantly in children/adolescents, and by chronic hepatic form in the young, especially among alcohol drinkers.

Restricted access carbon nanotube for microextraction by packed sorbent to determine antipsychotics in plasma samples by high-performance liquid chromatography-tandem mass spectrometry.

This manuscript describes the development of the restricted access carbon nanotube (RACNT) as a selective stationary phase for microextraction by packed sorbent (MEPS) to determine antipsychotics (chlorpromazine, clozapine, olanzapine, and quetiapine) in untreated plasma samples from schizophrenic patients by ultra-high liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The synthesis was achieved by chemically covering commercial multi-walled carbon nanotubes with bovine serum albumin (BSA) to subsequently pack the material in a polyethylene conical tube (1000 µL). The RACNTs' sorbents were able to exclude about 97% of the plasma proteins, maintaining the same performance for about 100 assays. The MEPS variables (sample pH, draw-eject cycles, desorption and phase cleanup) were evaluated to improve sensibility and selectivity. The MEPS/UHPLC-MS/MS method was linear at concentrations ranging from the lower limit of quantification (10.0 ng mL-1) to the upper limit of quantification (200-700 ng mL-1) with coefficients of determinations higher than 0.99. The precision assays presented relative standard deviation (RSD) values lower than 13%, and the accuracy assays presented relative error (RE) values that ranged from - 8.01 to 11.53%. Neither significant matrix effects nor carryover was observed. The developed method was successfully applied to determine antipsychotics drugs for therapeutic drug monitoring of schizophrenic patients.

Ultrasound evaluation of schistosomiasis-related morbidity among the Xakriabá people in the state of Minas Gerais, Brazil / Avaliação ultrassonográfica da morbidade por esquistossomose mansoni na população indígena Xakriabá, Minas Gerais, Brasil

Abstract Objective: To use ultrasound to investigate the morbidity related to schistosomiasis in the Xakriabá indigenous population. Materials and Methods: This was a field-based census study conducted in the territory of the Xakriabá people. A total of 166 individuals were invited, and 148 (≤ 77 years of age) agreed to participate. Most participants underwent abdominal ultrasound, physical examination, and stool examination. Mann-Whitney U and chi-square tests were used for comparisons. We determined risk by calculating odds ratio (OR) and performed logistic regression analysis. Results: Schistosoma mansoni eggs were found in 31 (26.7%) of the 116 stool samples examined, 22 (70.9%) of the 31 being from individuals 4-16 years of age. The median count was 144 eggs/g of feces (interquartile range, 264). Of the 105 participants examined with ultrasound, 68 (64.8%) had hepatomegaly (left lobe), 6 (5.7%) had splenomegaly, and 4 (3.8%) had portal hypertension. Egg-positive stool samples were more common in those with an enlarged left lobe (OR = 3.4; 95% confidence interval (CI): 1.1-11.2; p = 0.043). Periportal fibrosis was found in 30 participants (28.6%), of whom 9 (30%) had pattern C, 10 (33.3%) had pattern D, and 11 (36.7%) had pattern Dc. Age was the only independent risk factor for fibrosis (p = 0.007). Fibrosis was up to nine-fold more common in alcohol drinkers than in nondrinkers (OR = 9.28; 95% CI: 2.60-33.06; p < 0.001). Among the 138 participants in whom the clinical form was classified, the chronic hepatic form was identified in 54 (39.1%), of whom 32 (59.2%) were under 30 years of age and one (1.8%) was hepatosplenic. Conclusion: Schistosomiasis in the Xakriabá population is characterized by a high frequency of egg-positive stool samples, predominantly in children/adolescents, and by chronic hepatic form in the young, especially among alcohol drinkers.

Resumo Objetivo: Investigar a morbidade por esquistossomose na população indígena Xakriabá usando a ultrassonografia. Materiais e Métodos: Estudo de campo censitário realizado na terra da população indígena Xakriabá (166 convidados; 148 participantes; idade de 0-77). Foram feitos ultrassonografia abdominal, exame físico e coproscopia (EPF). Os testes Mann-Whitney U e qui-quadrado foram usados para comparações. Foram realizadas análise de risco (odds ratio - OR) e regressão logística. Resultados: De 116 índios com resultado de EPF, 31 (26,7%) tiveram ovos de Schistosoma; 22/31 (70,9%) tinham idade entre 4-16 anos. A carga parasitaria mediana foi 144 ovos/g (intervalo interquartílico: 264). De 105 examinados por ultrassom, 68 (64,8%) tiveram lobo hepático esquerdo aumentado, 6 (5,7%) tiveram esplenomegalia e 4 (3,8%) tiveram hipertensão portal. EPF+ foi mais frequente nos indivíduos com lobo esquerdo aumentado (OR: 3,4; intervalo de confiança (IC) 95%: 1,1-11,2; p = 0,043). Fibrose periportal ocorreu em 30/105 (28,6%) examinados, e desses 30, 9 (30%) apresentavam padrão C, 10 (33,3%) apresentavam padrão D e 11 (36,7%) apresentavam padrão Dc. A idade foi o único fator de risco independente para fibrose (p = 0,007). A fibrose ocorreu até nove vezes mais em usuários de álcool que em não usuários (OR: 9,28; IC 95%: 2,60-33,06; p < 0,001). Formas crônicas ocorreram em 54/138 (39,1%) participantes, sendo 32 dos 54 (64,8%) em menores de 30 anos; um (1,8%) era hepatoesplênico. Conclusão: A esquistossomose na população Xakriabá caracteriza-se por alta positividade, predomínio em crianças e presença de formas hepáticas crônicas em jovens, especialmente entre usuários de álcool.

Serum analysis in women and in vitro skin assay for the assessment of exposure to parabens in antiperspirants.

The present study assessed the exposure to methylparaben (MP) and propylparaben (PP) from antiperspirants in serum of 24 women aged 20-30 years old and an in vitro skin assay. An effective liquid chromatography-tandem mass spectrometry method for the determination of MP and PP levels in serum was developed and validated in the range of 10-100 µg/L; the method was fast, simple, sensitive, linear, precise, and accurate. In addition, a simple and rapid liquid chromatography-ultraviolet detection method for the determination of MP and PP levels in antiperspirants was developed and validated in the range of 2-26 mg/L, which presented satisfactory linearity, precision, and accuracy. Using these two methods, 20 commercial antiperspirants were evaluated, and only three showed MP and PP in the formulation. The antiperspirant containing 0.2% and 0.1% w/w MP and PP, respectively, was given to the volunteers, to estimate the internal dose, and submitted to a pig ear skin permeation assay in Franz diffusion cells, presenting a permeation flux of 32% for MP and 71% for PP. In this assay, both MP and PP permeated the skin; however, there was no correlation between antiperspirant use and paraben serum concentration in the volunteers. Graphical abstract.

Biological sample preparation by using restricted-access nanoparticles prepared from bovine serum albumin: application to liquid chromatographic determination of ß-blockers.

Restricted-access nanoparticles (RANPs) were prepared from bovine serum albumin by coacervation. They have an average sized of 311 nm. They were characterized and used to capture the ß-blockers atenolol, metoprolol and propranolol from untreated biological samples. It is shown that both high protein affinity drugs (propranolol) and low protein affinity drugs (atenolol) could be rapidly extracted from plasma. This is revealed by kinetic and isothermal adsorption studies. On the other hand, almost all proteins from the sample were excluded. This demonstrates the efficiency of RANPs as restricted-access material. Sample preparation was carried out by solid phase microextraction using a probe obtained by the fixation of the RANPs at the end of a glass capillary. Atenolol (in concentrations from 100 to 1200 µg L-1), metoprolol (from 80 to 1000 µg L-1) and propranolol (from 15 to 200 µg L-1) were extracted from spiked plasma samples and analyzed by LC MS/MS without using a separation column. Correlation coefficients >0.99, good precision, accuracy, robustness, and lack of memory effects were observed for all of the analytes. The detection limits (at an S/N of 3) are 25.6, 14.6, and 3.8 µg L-1 for atenolol, metoprolol and propranolol, respectively. Ten samples can be simultaneously extracted within ∼15 min. Plasma samples of patients undergoing medical treatment were successfully analyzed with the method. Graphical abstract Schematic representation of a bovine serum albumin-based restricted access nanoparticle that exclude proteins from a human plasma sample but capture the small analytes.

Label-free electrochemical DNA biosensor for zika virus identification.

Seventy years after its discovery, the zika virus emerged in Brazil and spread rapidly throughout the Americas, bringing unusual complications such as microcephaly. The World Health Organization classifies zika as the most harmful viral disease today and considers the development of new diagnostic methods for zika and related diseases, such as dengue, urgent. Although there are tests to identify both infections, current diagnostic methods are slow, nonspecific, and costly. This study describes an impedimetric electrochemical DNA biosensor for label-free detection of zika virus. Disposable electrodes were fabricated by thermal evaporation on polyethylene terephthalate substrates covered with a nanometric gold layer manufactured in three-contact configurations. The disposable, evaporated electrodes were morphologically characterized by atomic force microscopy and scanning electron microscopy. The electrode surface was characterized by electroanalytical techniques. Genetic sequences of primers and complementary capture probes were designed based on analysis of the zika and dengue virus genomes. The biosensor used a three-contact electrode to identify DNA sequences in a drop of sample, and for detection of zika virus sequences, it allowed for direct reading of the hybridization event without labeling on disposable electrodes and with a 1.5 h response time. In this system, impedance measurements indicated a limit of detection of 25.0 ±â€¯1.7 nM. The developed biosensors showed selectivity for zika in the synthetic DNA assays, and therefore, are promising for clinical analysis.

Online extraction of antihypertensive drugs and their metabolites from untreated human serum samples using restricted access carbon nanotubes in a column switching liquid chromatography system.

A novel analytical method was developed to determine 5 antihypertensive drugs of different pharmacological classes (angiotensin-converting enzyme inhibitors, calcium channel blockers, α-2 adrenergic receptor agonists, angiotensin II receptor blockers, and aldosterone receptor antagonists) and some of their metabolites in human serum. The untreated samples were directly analyzed in a column switching system using an extraction column packed with restricted access carbon nanotubes (RACNTs) in an ultra-high performance liquid chromatography coupled to a mass spectrometer (UHPLC-MS/MS). The RACNTs column was able to exclude approximately 100% of proteins from the samples in 2.0min, maintaining the same performance for about 300 analytical cycles. The method was validated in accordance with Food and Drug Administration (FDA) guidelines, being linear for all the determined analytes in their respective analytical ranges (coefficients of determination higher than 0.99) with limits of detection (LODs) and quantification (LOQs) ranging from 0.09 to 10.85µgL-1 and from 0.30 to 36.17µgL-1, respectively. High recovery values (88-112%) were obtained as well as suitable results for inter and intra-assay accuracy and precision. The method provided an analytical frequency of 5 samples per hour, including the sample preparation and separation/detection steps. The validated method was successfully used to analyze human serum samples of patients undergoing treatment with antihypertensive drugs, being useful for pharmacometabolomic, pharmacogenomic, and pharmacokinetic studies.

Direct extraction of tetracyclines from bovine milk using restricted access carbon nanotubes in a column switching liquid chromatography system.

This paper describes, for the first time, the use of restricted access carbon nanotubes (RACNTs) in the analysis of tetracyclines from milk samples, in a multidimensional liquid chromatographic system. Milk samples were initially acidified and centrifuged, and then the supernatant was directly analyzed in a column switching system in backflush configuration employing an extraction column of RACNTs. The sorbent was able to exclude all the remained proteins in less than 2.0min. The method was linear from 50 to 200µgL-1 and the coefficients of determination (r2) were 0.997, 0.992, 0.994 and 0.998 for oxytetracycline (OXI), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DOX), respectively. The analytical range included the maximum residue limits established by the regulatory agency.

New advances in restricted access materials for sample preparation: A review.

The determination of organic and inorganic analytes from biological samples need efficient sample preparation procedures in order to capture the analyte in a media with many macromolecules, which can cause analytical errors and problems with the instruments. Thus, "intelligent" sorbents, called restricted access materials (RAMs), have been widely used with these samples, due to their ability to retain analytes and exclude macromolecules. These materials have been obtained by modifying the external surfaces of conventional sorbents (e.g. polymers, carbon nanotubes, active carbon, and silica-based materials) with hydrophilic groups (chemical barrier), as well as by the presence of small pores (physical barrier) accessible only to low molecular weight molecules. Supramolecular solvents (SUPRAs) have also been used as RAMs, due to their abilities to exclude proteins according to size or through precipitation with the solvents. Therefore, due to the relevance of these materials, this review presents an overview of the most recent advances in obtaining RAMs based on silica, polymers, carbon nanotubes, (activated) carbon, and solvents, as well as their applications in biological sample preparation.

Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

Predictors of Very Late Events After Percutaneous Mitral Valvuloplasty in Patients With Mitral Stenosis.

Data on long-term outcomes of percutaneous mitral valvuloplasty (PMV) are still scarce. In addition, the persistence of pulmonary hypertension (PH) after PMV is a complication for which mechanisms and prognostic implications are unclear. Our aims were (1) to report the long-term outcomes of patients with rheumatic mitral stenosis treated with PMV; (2) to determine the risk factors for long-term poor outcomes; and (3) to analyze the prevalence and predictors of persistent PH. We prospectively enrolled 532 patients who underwent PMV from 1987 to 2011 at 2 hospitals. The following end points were assessed after PMV: all-cause mortality, mitral reintervention, a composite end point of all-cause mortality and mitral reintervention, and PH persistence. Survival status was available for 97% patients; the median follow-up was 10 years (interquartile range 4 to 18 years). Procedural success was achieved in 85% patients. During the follow-up, 21% patients died and 27% required mitral reintervention. Before PMV, 74% patients had PH that persisted after PMV in 45% of patients (p <0.001). Unfavorable valve anatomy (Wilkins score >8) and post-PMV mean pulmonary arterial pressure (PAP) were independent predictors of all-cause mortality, mitral reintervention, and the composite end point. Post-PMV mean PAP was significantly correlated with a mitral valve area (MVA) <2.5 cm(2) (p <0.001); in addition, on the echocardiographic follow-up, MVA was an independent predictor of systolic PAP (p <0.001). In conclusion, PMV represents an advantageous therapeutic option for patients with mitral stenosis in terms of long-term outcomes. Unfavorable valve anatomy and persistent PH were the most important predictors of long-term outcomes. The persistence of PH is associated with the MVA obtained after PMV.