Effervescence tablets based on magnetic ionic liquids as simple microdevices for the in situ dispersive liquid-liquid microextraction of urinary biomarkers.

BACKGROUND: Magnetic ionic liquids (MILs) have been explored in dispersive liquid-liquid microextraction (DLLME). Their usage allows to substitute centrifugation and/or filtration steps by a quick magnetic separation. Besides, effervescence-assisted DLLME is one of the most known options to improve the dispersion of the extractant in the sample, while allowing to avoid the consumption of external energy during dispersion. Despite these interesting features, only one study incorporates MILs containing the tetrachloroferrate anion in effervescence tablets. These MILs are highly viscous and liquid at room temperature, thus compromising the stability of the tablets when used as extraction microdevices in effervescence-assisted DLLME, and only allowing their use in the conventional MIL-DLLME mode. RESULTS: A new class of effervescence tablets containing a Ni(II)-based MIL, that is solid at room temperature, is here proposed. This type of tablets permits their use, for first time, in the in situ DLLME mode, occurring through the transformation of a water-soluble MIL into a water-insoluble MIL microdroplet. This way, the tablet formulation included: the MIL, the metathesis reagent lithium bis[(trifluoromethyl)sulfonyl]imide, NaH2PO4 and K2CO3 as effervescence precursors salts, and Na2SO4 as salting-out and desiccating agent. The method is combined with high-performance liquid-chromatography and both fluorescence and ultraviolet detection, for the determination of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and benzophenones (BPs), as biomarkers in urine. The method simply involved the addition of the effervescence tablet to the sample, thus taken place simultaneously the effervescence process and the metathesis reaction, without requiring any external energy consumption. The method presented limits of detection down to 10 ng L-1 for OH-PAHs and to 0.60 µg L-1 for BPs, inter-day relative standard deviations lower than 17 %, and average relative recoveries of 94 % in urine. The determined OH-PAHs contents in urine were between 0.40 and 16 µg L-1, and between 17.8 and 334 µg L-1 for BPs. SIGNIFICANCE: We have developed the first MIL-based effervescence tablets that are completely solid, thus improving the stability and robustness of these microdevices with respect to previously reported tablets involving MILs, while permitting to perform into the in situ DLLME mode (thus gaining in extraction efficiency). This approach including the MIL-based effervescence tablets constitutes an alternative on-site platform for the analysis of urine, as satisfactory precision, accuracy, and sensitivity are achieved despite not involving any external energy input within the analytical sample preparation setup. This method also constitutes the first application of MIL-based effervescence tablets for bioanalysis.

Toxicity and magnetometry evaluation of the uptake of core-shell maghemite-silica nanoparticles by neuroblastoma cells.

Nanoparticle uptake by cells is a key parameter in their performance in biomedical applications. However, the use of quantitative, non-destructive techniques to obtain the amount of nanoparticles internalized by cells is still uncommon. We have studied the cellular uptake and the toxicity of core-shell maghemite-silica magnetic nanoparticles (MNPs), with a core diameter of 9 nm and a shell thickness of 3 nm. The internalization of the nanoparticles by mouse neuroblastoma 2a cells was evaluated by sensitive and non-destructive Superconducting Quantum Interference Device (SQUID) magnetometry and corroborated by graphite furnace atomic absorption spectroscopy. We were thus able to study the toxicity of the nanoparticles for well-quantified MNP uptake in terms of nanoparticle density within the cell. No significant variation in cell viability or growth rate was detected for any tested exposure. Yet, an increase in both the amount of mitochondrial superoxide and in the lysosomal activity was detected for the highest concentration (100 µg ml-1) and incubation time (24 h), suggesting the onset of a disruption in ROS homeostasis, which may lead to an impairment in antioxidant responses. Our results validate SQUID magnetometry as a sensitive technique to quantify MNP uptake and demonstrate the non-toxic nature of these core-shell MNPs under our culture conditions.

Current state of proton therapy for tumors of the central nervous system in Spain: physical bases, indications, controversies and perspectives.

The unique biophysical properties of proton therapy (PT), regarding the precise dose distribution, a remarkable better sparing of surrounding normal tissues, and the decreasing costs have promoted the spread of this technique worldwide. In Spain, eleven new PT centers, added to the currently two in function, are expected to be available in the near future. Indications for PT are currently evolving. The suitability of PT in central nervous system tumors of the adult population has been extrapolated from the favorable experience in children and adolescents. Given the lack of appropriate randomized trials, controversies remain regarding its use in lower grade tumors, re-irradiation, and other clinical scenarios in which an a priori dose distribution benefit is expected compared to photon-based radiotherapy. PT is a reasonable option in many brain and spinal tumors associating long life expectancy, in which cognitive decline, and the appearance of radiation-induced neoplasms can be minimized.Estado actual de la terapia con protones en los tumores del sistema nervioso central en España: bases físicas, indicaciones, controversias y perspectivas.

De humani corporis fabrica, Libri septem (Andreas Vesalius, 1543) en México: Estudio Bibliológico del Primer Volumen en América / De humani corporis fabrica, Libri septem (Andreas Vesalius, 1543) in Mexico: Bibliologic Study of the First Volume in America

De humani corporis fabrica libri septem es un libro del médico y anatomista renacentista flamenco Andreas Vesalius (1514-1564), quien fue profesor de Anatomía en la Universidad de Padua y médico de la corte del emperador Carlos V. En ella se puede apreciar por primera vez a detalle, (en un compendio de siete libros), una lección académica docta de anatomía del cuerpo humano, basada en disecciones directas del cadáver, hecha y documentada por un joven profesor (Vesalio con 28 años), a sus alumnos de Medicina. Esta obra fue impresa en latín ciceroniano y publicada en Basilea en 1543 en el taller del humanista, lingüista e impresor Johannes Oporinus (1507-1568), e ilustrada probablemente, por artistas del taller de Ticiano como Jan Stephan van Calcar (1499-1546). Considerada hoy como una joya literaria, científica y artística, la fabrica de Vesalio de 1543, fue un hito en la Historia de la Medicina y es considerada como la obra fundacional de los atlas de anatomía modernos y el sustento del método de enseñanza de la disciplina en la carrera de Medicina en todo el mundo. Este volumen original mexicano, considerado hoy patrimonio de la humanidad por la UNESCO y primero de su tipo en América desde el siglo XVI, se encuentra en México como parte del acervo de libros raros y antiguos de la Biblioteca Palafoxiana en la ciudad de Puebla. En este artículo se describen y documentan por primera vez a detalle desde su fuente original, sus características.

SUMMARY: De humani corporis fabrica libri septem is a book written by the Flemish Renaissance physician and anatomist Andreas Vesalius (1514-1564), who was a professor of anatomy at the University of Padua and physician to the court of Emperor Charles V. It is in this book that for the very first time in detail, a learned academic lesson on the anatomy of the human body can be observed, in a compendium of seven books, based on direct dissections of the corpse, created and documented by a young professor (Vesalius at the age of 28) for his Medicine students. This work was printed in ciceronian latin and published in Basel in 1543 in the workshop of the humanist, linguist, and printer Johannes Oporinus (1507-1568), and illustrated by artists from the Titian workshop such as Jan Stephan van Calcar (1499-1546). Nowadays considered a literary, scientific and artistic jewel, Vesalius´fabrica of 1543 was a milestone in the history of medicine and is considered the foundation work of modern anatomy atlases, and basis for the teaching method of the discipline in medical careers worldwide. This original Mexican volume, is now considered part of UNESCO World Heritage and is the first book of its kind in America since the 16th century. It is part of the old and rare book collection of the Palafoxiana Library in the city of Puebla in Mexico. In this article, its characteristics are described and for the first time, documented in detail from its original source.

Promising anti-proliferative indolic benzenesulfonamides alter mechanisms with sulfonamide nitrogen substituents.

Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5-trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7-109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to non-tumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G2/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.

Columnar Mesomorphism in a Methylthio-Decorated Triindole for Enhanced Charge Transport.

We report a semiconducting triindole-based discotic liquid crystal (TRISMe) functionalized with six p-methylthiophenyl groups at its periphery. While initially a crystalline solid at room temperature, TRISMe transitions to a columnar hexagonal mesophase upon heating and retains this supramolecular organization upon subsequent cooling, despite having only three flexible alkyl chains attached to the core's nitrogens. The incorporation of methylthio groups effectively hinders tight molecular packing, stabilizing the columnar arrangement of this disk-shaped molecule. Single crystal analysis confirmed the high tendency of this compound to organize into a columnar architecture and the role played by the methylthio groups in reinforcing such structure. The mesomorphic behavior of TRISMe provides an opportunity for processing from its molten state. Notably, our research reveals significant differences in charge transport depending on the processing method, whether solution drop-casting or melt-based. TRISMe shows hole mobility values averaging 3 × 10-1 cm2 V-1 s-1 when incorporated in diode-type devices from the isotropic melt and annealed at the mesophase temperature, estimated by SCLC (space-charge-limited current) measurements. However, when integrated into solution-processed organic field-effect transistors (OFETs), crystalline TRISMe exhibits a hole mobility of 3 × 10-4 cm2 V-1 s-1. The observed differences can be attributed to a beneficial supramolecular assembly achieved in the mesophase in spite of its lower order. These results emphasize the material's potential for applications in easy-to-process electronic devices and highlight the potential of methylthio moieties in promoting columnar mesophases.

Prevalence of Computer Vision Syndrome and Its Risk Factors in a Spanish University Population.

OBJECTIVES: To determine the prevalence of digital eye strain or computer vision syndrome (CVS) and its risk factors in a university population (University of Valladolid, Spain). METHODS: An anonymous cross-sectional online survey was conducted in a university population [staff (lecturers and administrative employees) and students (undergraduate, master's, and PhD)], including two validated questionnaires (Ocular Surface Disease Index [OSDI] and the 17-item Computer-Vision Symptom Scale questionnaire [CVSS17]) and questions about sociodemographic data and visual display terminal use. The prevalence and risk factors for CVS (CVSS17≥29) (multivariate logistic regression model) were calculated. RESULTS: One thousand nine participants responded to the survey (35.2±15.2 years; 64.1% women). The mean OSDI and CVSS17 questionnaire scores were 18.9±15.6 and 31.5±6.4, respectively, and 35.4% of the respondents had dry eye symptoms (OSDI>22). The total prevalence of CVS was 65.4% (95% CI 62.1-68.3). Undergraduate students showed the highest CVS prevalence (72.6%; P <0.01), which was significant. In addition, women, participants younger than 36 years old, contact lens wearers, and subjects with dry eye symptoms reported a statistically higher CVSS17 score ( P ≤0.01). In the multivariate model, significant factors associated with the presence of CVS ( P ≤0.03) were female sex (OR=2.10; 95% CI 1.54-2.88), dry eye symptoms (OSDI>22) (OR=16.98; 95% CI 10.36-27.84), VTD use ≥6 hr daily (OR=1.96; 95% CI 1.09-3.52), and being an undergraduate student (OR=2.23; 95% CI 1.54-3.24). CONCLUSION: A high prevalence (65.4%) of CVS was found among the Spanish university population, with the undergraduate student group having the highest prevalence (72.6%). Female sex, more than 6 hr/day of visual display terminal use, being an undergraduate student, and dry eye symptoms significantly increased the risk of CVS in the university population.

Magnetic anisotropy engineering in onion-structured metal oxide nanoparticles combining dual exchange coupling and proximity effects.

A series of exchange-coupled magnetic nanoparticles combining several magnetic phases in an onion-type structure were synthesized by performing a three-step seed-mediated growth process. Iron and cobalt precursors were alternatively decomposed in high-boiling-temperature solvents (288-310 °C) to successively grow CoO and Fe3-δO4 shells (the latter in three stages) on the surface of Fe3-δO4 seeds. The structure and chemical composition of these nanoparticles were investigated in depth by combining a wide panel of advanced techniques, such as scanning transmission electron microscopy (STEM), electron energy-loss spectroscopy-spectrum imaging (EELS-SI), 57Fe Mössbauer spectrometry, and X-ray circular magnetic dichroism (XMCD) techniques. The size of the nanoparticles increased progressively after each thermal decomposition step, but the crystal structure of core-shell nanoparticles was significantly modified during the growth of the second shell. Indeed, the antiferromagnetic CoO phase was progressively replaced by the CoFe2O4 ferrimagnet due to the concomitant processes of partial solubilization/crystallization and the interfacial cationic diffusion of iron. A much more complex chemical structure than that suggested by a simple size variation of the nanoparticles is thus proposed, namely Fe3-δO4@CoO-CoFe2O4@Fe3-δO4, where an intermediate Co-based layer was shown to progressively become a single, hybrid magnetic phase (attributed to proximity effects) with a reduction in the CoO amount. In turn, the dual exchange-coupling of this hybrid Co-based intermediate layer (with high anisotropy and ordering temperature) with the surrounding ferrite (core and outer shells) stabilized the particle moment well above room temperature. These effects allow for the production of Fe oxide-based magnetic nanoparticles with high effective anisotropy, thus revealing the potential of this strategy to design rare-earth-free permanent nanomagnets at room temperature.

T3-T4 index as a prognostic marker of response to biological treatments in elderly patients with inflammatory bowel disease.

Following the growing trend of trying to individualise treatment in inflammatory bowel disease and in view of the challenge posed by elderly patients requiring biologic treatments, we have conducted a study in our centre to assess the T3/T4 index as a predictor of response to biologic treatments in elderly patients.

Exploring a new generation of bimetallic magnetic ionic liquids with ultra-low viscosity in microextraction that enable direct coupling with high-performance liquid-chromatography.

BACKGROUND: The incorporation of bimetallic magnetic ionic liquids (MILs) in microextraction methods is an emerging trend due to the improved magnetic susceptibility offered by these solvents, which relies on the presence of metallic components in both the cation and the anion. This feature favors easy magnetic separation of these solvents in analytical sample preparation strategies. However, reported liquid-phase microextraction methods based on bimetallic MILs still present an important drawback in that the MILs are highly viscous, making a dispersive solvent during the microextraction procedure necessary, while also requiring a tedious back-extraction step prior to the chromatographic analysis. RESULTS: We propose for the first time a new generation of ultra-low viscosity bimetallic MILs composed of two paramagnetic Mn(II) complexes characterized by their easy usage in dispersive liquid-liquid microextraction (DLLME). The approach does not require dispersive solvent and the MIL-DLLME setup was directly combined with high-performance liquid chromatography (HPLC) and fluorescence detection (FD), without any back-extraction step. The approach was evaluated for the determination of five monohydroxylated polycyclic aromatic hydrocarbons, as carcinogenic biomarkers, in human urine. Optimum conditions of the MIL-DLLME method included the use of a low MIL volume (75 µL), a short extraction time (5 min), and no need of any dispersive solvent neither NaCl. The method presented limits of detection down to 7.50 ng L-1, enrichment factors higher than 17, and provided inter-day relative standard deviation lower than 11%. Analysis of urine samples was successfully performed, with biomarker content found at levels between 0.24 and 7.8 ng mL-1. SIGNIFICANCE: This study represents the first liquid-phase microextraction method using the new generation of low-viscous bimetallic MILs. The proposed MIL-DLLME approach represents 2 important advances with respect to previous methods employing bimetallic MILs: 1) no dispersive solvent is required, and 2) direct injection of the MIL in the HPLC is possible after minor dilution (no back extraction steps are required). Therefore, the microextraction strategy is simple, rapid, and consumes very small amounts of energy.

The Repeatability and Agreement of Ocular Parameters Measured with the MYAH and Myopia Master Devices between Expert and Non-Expert Practitioners.

In myopia control, it is essential to measure the axial length (AL) and corneal parameters, and to monitor whether changes in these parameters have occurred over time. The aim of this study was to analyse the repeatability and agreement between expert and non-expert practitioners in ocular parameters measured by the MYAH and Myopia Master. Three repeated measurements (n = 42) were recorded with the MYAH and Myopia Master by two (an expert and a non-expert) observers in a randomized order. The AL, K1, K2, and white-to-white (WTW) distance were collected. The intraobserver repeatability was excellent in all parameters measured with both devices in both observers. The AL outcome presented the best repeatability with the MYAH and Myopia Master (intraclass correlation coefficient, ICC = 1.0; coefficient of variation, CV ≤ 0.06% for both observers), while the WTW presented poorer results (ICC ≤ 0.991; CV ≤ 0.52%). The Myopia Master provides a significantly (p ≤ 0.01) flatter K1 and K2 as well as a lower WTW (p ≤ 0.01) than the MYAH. No statistically significant difference in AL measurements was found with either device (p ≥ 0.10; ICC = 1.0). None of the parameters showed differences (p ≥ 0.12) between the expert and non-expert observer. The MYAH and Myopia Master provide consistent measurements in a healthy adult population regardless of the previous clinical experience of the observer. AL measurements should be used interchangeably but K1, K2, and WTW should be used interchangeably with caution.

Fully Automated Flow Protocol for C(sp3)-C(sp3) Bond Formation from Tertiary Amides and Alkyl Halides.

Herein, we present a novel C(sp3)-C(sp3) bond-forming protocol via the reductive coupling of abundant tertiary amides with organozinc reagents prepared in situ from their corresponding alkyl halides. Using a multistep fully automated flow protocol, this reaction could be used for both library synthesis and target molecule synthesis on the gram-scale starting from bench-stable reagents. Additionally, excellent chemoselectivity and functional group tolerance make it ideal for late-stage diversification of druglike molecules.

Clinical and laboratory features of rickettsioses in Yucatan, Mexico.

Rickettsia species are obligate intracellular bacteria that can cause mild to severe human disease. Based on phylogeny, clinical symptoms, and antigenic properties, rickettsiae are classified into four groups. Infections by these agents are characterized by clinical symptoms ranging from self-limited to severe and even fatal febrile illnesses, depending on the Rickettsia spp. involved, the patient's predisposition, and timely medical care. The present study aimed to characterize rickettsial diseases in Yucatan according to clinical and laboratory features appearing in medical records corresponding to 427 samples taken between 2015 and 2018. A study was conducted over the period 2015-2018 on 427 samples. Clinical and laboratory features were documented from the patients' medical records. For molecular diagnosis, blood was collected in 3.8 % sodium citrate as anticoagulant, and DNA was extracted. Single-step and nested PCR amplification was performed using genus-specific primers for the rickettsial 17kDa and ompB genes. The amplicons obtained were purified and sequenced. A total of 22.7 % (97/427) positive cases of Rickettsia spp. were identified by PCR from 14.15 % (15/106) of the municipalities in Yucatan. 75.2 % (73/97) of the cases were from the city of Merida during the autumn (September-December). The age groups with the highest frequency of confirmed cases were pediatric (5-14 years) (57.7 %) and adults (25-49 years) (42.2 %). There were six fatal cases in children, one associated with R. typhi and five with R. rickettsii. In non-fatal cases, 32.9 % (32/97) corresponded to the spotted fever group (SFG), and 60.8 % (59/97) to the typhus group (TG). Significant differences in signs, and laboratory data, were observed between the pediatric and adult populations. For the treatment of patients, oral and intravenous doxycycline was used in severe hospitalized cases. Typhus group and spotted fever group Rickettsiae are endemic pathological agents found in urban and rural areas of our region. Molecular identification allows for greater diagnostic accuracy and timely treatment and consequently a better prognosis. It is necessary to implement or reinforce measures focused on the dissemination of knowledge regarding rickettsial diseases and their prevention.

ffectiveness and safety of ustekinumab dose escalation in Crohn’s disease: a multicenter observational study / Efectividad y seguridad del aumento de dosis de ustekinumab en la enfermedad de Crohn: un estudio observacional multicéntrico

Background: ustekinumab has proven effective in Crohn’s disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. Aim: to evaluate the effectiveness of ustekinumab dose escalation in CD. Methods: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. Results: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. Conclusion: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.(AU)

A dynamical method to objectively assess infantile nystagmus based on eye tracking. A pilot study

Purpose The purpose of this research is to propose a new method for the easy, inexpensive and objective quantification of nystagmus using eye-tracking records collected during a simple reading task that could be implantable in clinical practice to assess patients with nystagmus. Methods This is a prospective, observational pilot study. Eye movements of 4 nystagmus patients and 9 healthy children during a reading task (a paragraph with 82 words) on a 15′’ monitor were collected and compared. Data are time series indicating the gaze position on the screen. Two quantifiers were proposed: IndS (based on the speed of movements) and IndF (based on the variation of the gaze trajectory). Results The indices proposed reflect differences in the behavior of eye movements between the two groups. Nystagmus patients present higher values of IndS - indicating smaller number of slow movements (16% of movements with speeds <0.33 1/s for nystagmus and 85% for the control group, with p = 0.01) - and higher values of IndF - indicating higher gaze fluctuation (p = 0.01). Differences were not related with reading speed as show the mean and standard deviation: the nystagmus group required 115±45 s to complete the task and the control group 151±85 s; p = 0.73. Conclusions The proposed indices provide a new method that allows an objective assessment of nystagmus, with potential use in clinical and research practice to improve the follow-up of patients by monitoring the nystagmus over time or treatment. (AU)

Comparison of the Ocular Surface Disease Index and the Symptom Assessment in Dry Eye Questionnaires for Dry Eye Symptom Assessment.

BACKGROUND: Patient-reported dry eye symptoms (DESs), assessed using the Ocular Surface Disease Index (OSDI) and the Symptom Assessment iN Dry Eye (SANDE) questionnaires, were compared in a large sample of patients. METHODS: The correlation (Spearman coefficient) and agreement (Bland-Altman analysis) between the OSDI and SANDE questionnaire scores (with and without score normalization) were assessed in 1033 patients and classified according to the OSDI score as non-DES and DES in a cross-sectional analysis. RESULTS: The normalized and non-normalized SANDE results were higher than the OSDI results in all samples (2.83 ± 12.40 (p = 0.063) and 2.85 ± 15.95 (p = 0.016), respectively) and in non-DES (p > 0.063) and DES (p < 0.001) with both OSDI cutoff values. Weak correlations were found (Spearman coefficient <0.53; p < 0.001) in all cases except DES (0.12, p = 0.126). Weak agreement was found with a Bland-Altman analysis of the normalized and non-normalized scores of both questionnaires (mean difference from -7.67 ± 29.17 (DES patients) to -1.33 ± 8.99 (non-DES patients) without score normalization, and from -9.21 ± 26.37 (DES patients) to -0.85 ± 4.01 (non-DES) with data normalization), with a statistically significant linear relationship (R2 > 0.32, p < 0.001). The SANDE questionnaire did not yield the same patient classification as OSDI. The same operative curves (ROC) of the SANDE normalized and non-normalized scores were used to differentiate among patients with DES using OSDI < 12 (0.836 ± 0.015) or OSDI < 22 (0.880 ± 0.015) cutoff values. CONCLUSIONS: Normalized and non-normalized data collected from the SANDE questionnaire showed relevant differences from those of the OSDI, which suggests that the results of the SANDE visual analog scale-based questionnaire provide different patient classifications than the OSDI score.

A tool to assess analytical sample preparation procedures: Sample preparation metric of sustainability.

Sample preparation is a key step in most analytical methods, generally regarded as the least green step of the entire procedure. The existing green metrics assess the greenness of sample preparation techniques through the evaluation of the whole analytical procedure: including sampling, sample preparation, and the final detection/quantitation. Such inclusion of the entire method makes assessing the sustainability of a newly developed sample preparation technique quite challenging, as many aspects not solely linked to the sample preparation step are unavoidably considered. Thus, an alternative metric that can explicitly and exclusively evaluate the sample preparation is proposed. The metric is simple; it reports the result with a clock-like diagram, displaying the greenness outcome of main sample preparation parameters and a total score. This new metric can differentiate closely related microextraction approaches in terms of sustainability. The metric is also open-source and can be used by downloading the Excel sheet provided.

Understanding the Raman enhancement of carbon nanohorns labelled with organic dyes.

Carbon nanohorns have been non-covalently functionalized with two different benzothiadiazoloquinoxalines prepared via Stille cross-coupling reactions under solvent-free conditions and microwave irradiation. The close interactions between these organic molecules and the nanostructures resulted in a prominent Raman enhancement, which makes them attractive candidates for multiple applications. A complete experimental physico-chemical characterization has been combined with in silico studies to understand these phenomena. The processability of the hybrids was exploited to prepare homogeneous films on substrates with different natures.

Effectiveness and safety of ustekinumab dose escalation in Crohn's disease: a multicenter observational study.

BACKGROUND: ustekinumab has proven effective in Crohn's disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. AIM: to evaluate the effectiveness of ustekinumab dose escalation in CD. METHODS: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. RESULTS: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. CONCLUSION: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.

Intrasession repeatability and agreement of a new method to measure the foveal fixation axis.

Purpose: Ophthalmic lens adaptation, particularly with progressive addition lenses, requires accurate measurements of the patient nasopupillary distance (NPD) and interpupillary distance (IPD), which are usually collected using the pupil centre as a reference. However, differences between the pupil centre and visual or foveal axis could induce some subsidiary effects of correcting lenses. This study aimed to assess the intrasession repeatability of a new prototype (Ergofocus®; Lentitech, Barakaldo, Spain) that can measure the foveal fixation axis (FFA) distance and assess the agreement with the NPD measurements collected using a traditional method (frame ruler). Methods: The FFA at far and near distances was measured three consecutive times in 39 healthy volunteers to determine the intrasession repeatability according to the British Standards Institute and International Organization for Standardization. Additionally, the FFA and NPD (standard frame ruler) were measured in 71 healthy volunteers and compared using Bland-Altman analysis. Two blinded experienced practitioners conducted each FFA and NPD measurement. Results: The FFA measurements showed acceptable repeatability at far distances (right eye (RE): Sw = 1.16 ± 0.76 mm and coefficient of variation (CV) = 3.92 ± 2.51%; left eye (LE) Sw = 1.11 ± 0.79 mm and CV = 3.76 ± 2.51%) and at near distances (RE: Sw = 0.97 ± 0.85 mm and CV = 3.52 ± 3.02%; LE: Sw = 1.17 ± 0.96 mm and CV = 4.54 ± 3.72%). Additionally, agreement with the NPD showed large differences at far distances (RE: -2.15 ± 2.34, LoA = -6.73 to 2.43 mm (P < 0.001); LE: -0.61 ± 2.62, LoA = -5.75 to 4.53 mm (P = 0.052)) and near distances (RE: -3.08 ± 2.80, LoA -8.57 to 2.42 mm (P < 0.001); LE: -2.97 ± 3.97, LoA: -10.75 to 4.80 mm (P < 0.001)). Conclusions: FFA measurements showed clinically acceptable repeatability at both far and near distances. Agreement with the NPD measured using a standard frame ruler showed significant differences, suggesting that both measurements are not interchangeable in clinical practice to prescribe and center ophthalmic lenses. Further research is necessary to assess the impact of FFA measurement in ophthalmic lens prescriptions.