E-consults between primary care and internal medicine: implementation, accessibility, benefits, and implications.

AIM: This work aims to evaluate whether electronic consultations (e-consults) are a clinically useful, safe tool for assessing patients between primary care and internal medicine. METHODS: This is a retrospective cohort study of all e-consults ordered by the Primary Care Department to the Internal Medicine Department between September 2019 and December 2023. The results of initial consultations, emergency department visits and subsequent admissions, and survival were assessed and complaints and claims filed were reviewed. RESULTS: A total of 11,434 e-consults were recorded (55.4% women) with a mean age of 62.1 (SD19.4) years and a wide range (15-102 years). The mean response time was 2.55 (SD 1.6) days. As a result of the e-consults, 5645 patients (49.4%) were given an in-person appointment. For the remaining 5789 (50.6%), a written response was provided. Among those given appointments, the time between the response and in-person appointment was less than five days (95% of cases). Compared to those not given appointments, in-person appointments were older (p < 0.0001), visited the emergency department more times (one month: p = 0.04; three months: p = 0.001), were admitted to the hospital more times (one month: p = 0.0001; three months: p = 0.0001), and had higher mortality at one year (12.7% vs. 9.8% p = 0.0001). In the Cox analysis, only in-person appointments (RR = 1.11; p = 0.04)) and age (RR = 1.09; p < 0.01) were independent factors of mortality. No complaints or claims of any kind were registered. CONCLUSIONS: These data suggest that e-consults are a clinically useful, safe tool for assessing patients referred from primary care to internal medicine departments.

Analysis of Milk Using a Portable Potentiometric Electronic Tongue Based on Five Polymeric Membrane Sensors.

A portable potentiometric electronic tongue (PE-tongue) was developed and applied to evaluate the quality of milk with different fat content (skimmed, semi-skimmed, and whole) and with different nutritional content (classic, calcium-enriched, lactose-free, folic acid-enriched, and enriched in sterols of vegetal origin). The system consisted of a simplified array of five sensors based on PVC membranes, coupled to a data logger. The five sensors were selected from a larger set of 20 sensors by applying the genetic algorithm (GA) to the responses to compounds usually found in milk including salts (KCl, CaCl2, and NaCl), sugars (lactose, glucose, and galactose), and organic acids (citric acid and lactic acid). Principal component analysis (PCA) and support vector machine (SVM) results indicated that the PE-tongue consisting of a five-electrode array could successfully discriminate and classify milk samples according to their nutritional content. The PE-tongue provided similar discrimination capability to that of a more complex system formed by a 20-sensor array. SVM regression models were used to predict the physicochemical parameters classically used in milk quality control (acidity, density, %proteins, %lactose, and %fat). The prediction results were excellent and similar to those obtained with a much more complex array consisting of 20 sensors. Moreover, the SVM method confirmed that spoilage of unsealed milk could be correctly identified with the simplified system and the increase in acidity could be accurately predicted. The results obtained demonstrate the possibility of using the simplified PE-tongue to predict milk quality and provide information on the chemical composition of milk using a simple and portable system.

Promoting laccase sensing activity for catechol detection using LBL assemblies of chitosan/ionic liquid/phthalocyanine as immobilization surfaces.

The performance of electrochemical laccase-based biosensors can be improved by immobilizing the enzyme on composite Layer-by-Layer (LbL) supports in which materials with complementary functions are combined. LbL films are formed by layers combining an electrocatalytic material which favors electron transfer (sulfonated copper phthalocyanine, CuPcS(-)), an ionic liquid which enhances the electrical conductivity of the layers (1-butyl-3-methylimidazolium tetrafluoroborate, IL(+)) and a material able to promote enzyme immobilization (chitosan, CHI(+)). Composite films with different structures have been demonstrated to be efficient electrocatalysts, producing an increase in the magnitude of the responses towards catechol. The most intense and reproducible electrocatalytic effect was observed when a layer of the CuPcS(-) was placed on top of a layer formed by a mixture of CHI(+) + IL(+) to obtain [CHI(+) + IL(+)|CuPcS(-)]2 films. Biosensors with laccase immobilized on the surface of the LbL layers [CHI(+) + IL(+)|CuPcS(-)]2|Lac showed mediated electron transfer between the redox enzyme and the film and a reproducibility of device-to-device performance of 4.1%. The amperometric biosensor showed a sensitivity of 0.237 A·M-1 and a linear detection range from 2.4 µM to 26 µM for catechol. The excellent Limit of detection (LOD) of 8.96·10-10 M (3·σ /m) is one order of magnitude lower than that obtained in similar studies. A Michaelis-Menten constant of 3.16 µM confirms excellent enzyme-substrate affinity.

Analysis of musts and wines by means of a bio-electronic tongue based on tyrosinase and glucose oxidase using polypyrrole/gold nanoparticles as the electron mediator.

A bioelectronic tongue (bioET) based on combinations of enzymes (tyrosinase and glucose oxidase) and polypyrrole (Ppy) or polypyrrole/AuNP (Ppy/AuNP) composites was build up and applied to the analysis and discrimination of musts and wines. Voltammetric responses of the array of sensors demonstrated the effectiveness of polymers as electron mediators and the existence of favorable synergistic effects between Ppy and the AuNPs. Using Principal Component Analysis and Parallel Factor Analysis it was possible to discriminate musts according to the °Brix and TPI (Total Polyphenol Index), and wines according to the alcoholic degree and TPI. Partial Least Squares provided good correlations between the bioET output and traditional chemical parameters. Moreover, Support Vector Machines permitted to predict the TPI and the alcoholic degree of wines, from data provided by the bioET in the corresponding grapes. This result opens the possibility to predict wine characteristics from the beginning of the vinification process.

Array of biosensors for discrimination of grapes according to grape variety, vintage and ripeness.

A bioelectronic tongue based on nanostructured biosensors specific for the simultaneous detection of sugars and phenols has been developed. The array combined oxidases and dehydrogenases immobilized on a lipidic layer prepared using the Langmuir-Blodgett technique where Glucose oxidase, d-Fructose dehydrogenase, Tyrosinase or Laccase were imbibed. A phthalocyanine was co-immobilized in the sensing layer and used as electron mediator. The array thus formed has been used to analyze grapes and provides global information about the samples while providing specific information about their phenolic and their sugar content. Using Principal Component Analysis (PCA) the array of voltammetric biosensors has been successfully used to discriminate musts prepared from different varieties of grapes (Tempranillo, Garnacha, Cabernet-Sauvignon, Prieto Picudo and Mencía). Differences could be also detected between grapes of the same variety and cultivar harvested in two successive vintages (2012 and 2013). Moreover, the ripening of grapes could be monitored from veraison to maturity due to the changes in their phenolic and sugar content. Using Partial Least Squares (PLS-1) analysis, excellent correlations have been found between the responses provided by the array of biosensors and classical parameters directly related to phenols (total polyphenol index, TPI) and sugar concentration (degree Brix) measured by chemical methods with correlation coefficients close to 1 and errors close to 0. It is also worthy to notice the good correlations found with parameters associated with the pH and acidity that can be explained by taking into account the influence of the pH in the oxidation potentials of the phenols and in the enzymatic activity. This bioelectronic tongue can assess simultaneously the sugar and the phenolic content of grapes and could be used to monitor the maturity of the fruit and could be adapted easily to field analysis.

Analysis of organic acids and phenols of interest in the wine industry using Langmuir-Blodgett films based on functionalized nanoparticles.

A chemically modified electrode consisting of Langmuir-Blodgett (LB) films of n-dodecanethiol functionalized gold nanoparticles (SDODAuNP-LB), was investigated as a voltammetric sensor of organic and phenolic acids of interest in the wine industry. The nanostructured films demonstrated interfacial properties being able to detect the main organic acids present in grapes and wines (tartaric, malic, lactic and citric). Compared to a bare ITO electrode, the modified electrodes exhibited a shift of the reduction potential in the less positive direction and a marked enhancement in the current response. Moreover, the increased electrocatalytic properties made it possible to distinguish between the different dissociable protons of polyprotic acids. The SDODAuNP-LB sensor was also able to provide enhanced responses toward aqueous solutions of phenolic acids commonly found in wines (caffeic and gallic acids). The presence of nanoparticles increased drastically the sensitivity toward organic acids and phenolic compounds. Limits of detection as low as 10(-6) mol L(-1) were achieved. Efficient catalytic activity was also observed in mixtures of phenolic acid/tartaric in the range of pHs typically found in wines. In such mixtures, the electrode was able to provide simultaneous information about the acid and the phenol concentrations with a complete absence of interferences. The excellent sensing properties shown by these sensors could be attributed to the electrocatalytic properties of the nanoparticles combined with the high surface to volume ratio and homogeneity provided by the LB technique used for the immobilization. Moreover, the LB technique also provided an accurate method to immobilize the gold nanoparticles giving rise to stable and reproducible sensors showing repeatability lower than 2% and reproducibility lower than 4% for all the compounds analyzed.

Improved selectivity towards NO2 of phthalocyanine-based chemosensors by means of original indigo/nanocarbons hybrid material.

A new and original gas sensor-system dedicated to the selective monitoring of nitrogen dioxide in air and in the presence of ozone, has been successfully achieved. Because of its high sensitivity and its partial selectivity towards oxidizing pollutants (nitrogen dioxide and ozone), copper phthalocyanine-based chemoresistors are relevant. The selectivity towards nitrogen dioxide results from the implementation of a high efficient and selective ozone filter upstream the sensing device. Thus, a powdered indigo/nanocarbons hybrid material has been developed and investigated for such an application. If nanocarbonaceous material acts as a highly permeable matrix with a high specific surface area, immobilized indigo nanoparticles are involved into an ozonolysis reaction with ozone leading to the selective removal of this analytes from air sample. The filtering yields towards each gas have been experimentally quantified and establish the complete removal of ozone while having the concentration of nitrogen dioxide unchanged. Long-term gas exposures reveal the higher durability of hybrid material as compared to nanocarbons and indigo separately. Synthesis, characterizations by many complementary techniques and tests of hybrid filters are detailed. Results on sensor-system including CuPc-based chemoresistors and indigo/carbon nanotubes hybrid material as in-line filter are illustrated. Sensing performances will be especially discussed.

Evaluation of oxygen exposure levels and polyphenolic content of red wines using an electronic panel formed by an electronic nose and an electronic tongue.

An electronic panel formed by an electronic nose and an electronic tongue has been used to analyse red wines showing high and low phenolic contents, obtained by flash release and traditional soaking, respectively, and processed with or without micro-oxygenation. Four oxygen transfer rate conditions (0.8, 1.9, 8.0, and 11.9 µl oxygen/bottle/day) were ensured by using synthetic closures with controlled oxygen permeability and storage under controlled atmosphere. Twenty-five chemical parameters associated with the polyphenolic composition, the colour indices and the levels of oxygen were measured in triplicate and correlated with the signals registered (seven replicas) by means of the electronic nose and the electronic tongue using partial least squares regression analysis. The electronic nose and the electronic tongue showed particularly good correlations with those parameters associated with the oxygen levels and, in particular, with the influence of the porosity of the closure to oxygen exposure. In turn, the electronic tongue was particularly sensitive to redox species including oxygen and phenolic compounds. It has been demonstrated that a combined system formed from the electronic nose and the electronic tongue provides information about the chemical composition of both the gas and the liquid phase of red wines. This complementary information improves the capacity to predict values of oxygen-related parameters, phenolic content and colour parameters.

Bioelectronic tongue based on lipidic nanostructured layers containing phenol oxidases and lutetium bisphthalocyanine for the analysis of grapes.

In this work, a multisensor system formed by nanostructured voltammetric biosensors based on phenol oxidases (tyrosinase and laccase) has been developed. The enzymes have been incorporated into a biomimetic environment provided by a Langmuir-Blodgett (LB) film of arachidic acid (AA). Lutetium bisphthalocyanine (LuPc2) has also been introduced in the films to act as electron mediator. The incorporation of the enzymes to the floating layers to form Tyr/AA/LuPc2 and Lac/AA/LuPc2 films has been confirmed by the expansion in the surface pressure isotherms and by the AFM images. The voltammetric response towards six phenolic compounds demonstrates the enhanced performance of the biosensors that resulted from a preserved activity of the tyrosinase and laccase combined with the electron transfer activity of LuPc2. Biosensors show improved detection limits in the range of 10(-7)-10(-8) mol L(-1). An array formed by three sensors AA/LuPc2, Tyr/AA/LuPc2 and Lac/AA/LuPc2 has been employed to discriminate phenolic antioxidants of interest in the food industry. The Principal Component Analysis scores plot has demonstrated that the multisensor system is able to discriminate phenols according to the number of phenolic groups attached to the structure. The system has also been able to discriminate grapes of different varieties according to their phenolic content. This good performance is due to the combination of four factors: the high functionality of the enzyme obtained using a biomimetic immobilization, the signal enhancement caused by the LuPc2 mediator, the improvement in the selectivity induced by the enzymes and the complementary activity of the enzymatic sensors demonstrated in the loading plots.

Structural and electrochemical properties of lutetium bis-octachloro-phthalocyaninate nanostructured films. Application as voltammetric sensors.

Thin films of the bis[2,3,9,10,16,17,23,24-octachlorophthalocyaninate] lutetium(III) complex (LuPc2Cl32) have been prepared by the Langmuir-Blodgett and the Langmuir-Schaefer (LS) techniques. The influence of the chlorine substituents in the structure of the films and in their spectroscopic, electrochemical and sensing properties has been evaluated. The π-A isotherms exhibit a monolayer stability greater than the observed in the unsubstituted analogue (LuPc2), being easily transferred to solid substrates, also in contrast to LuPc2. The LB and LS films present a linear growth forming stratified layers, monitored by UV-VIS absorption spectroscopy. The latter also revealed the presence of LuPc2Cl32 in the form of monomers and aggregates in both films. The FTIR data showed that the LuPc2Cl32 molecules present a non-preferential arrangement in both films. Monolayers of LB and LS were deposited onto 6 nm Ag island films to record surface-enhanced resonance Raman scattering (SERRS), leading to enhancement factors close to 2 x 10(3). Finally, LB and LS films deposited onto ITO glass have been successfully used as voltammetric sensors for the detection of catechol. The improved electroactivity of the LB and LS films has been confirmed by the reduction of the overpotential of the oxidation of catechol. The enhancement of the electrocatalytic effect observed in LB and LS films is the result of the nanostructured arrangement of the surface which increases the number of active sites. The sensors show a limit of detection in the range of 10(-5) mol/L.

Application of multi-way analysis to UV-visible spectroscopy, gas chromatography and electronic nose data for wine ageing evaluation.

In this study, a multi-way method (Tucker3) was applied to evaluate the performance of an electronic nose for following the ageing of red wines. The odour evaluation carried out with the electronic nose was combined with the quantitative analysis of volatile composition performed by GC-MS, and colour characterisation by UV-visible spectroscopy. Thanks to Tucker3, it was possible to understand connections among data obtained from these three different systems and to estimate the effect of different sources of variability on wine evaluation. In particular, the application of Tucker3 supplied a global visualisation of data structure, which was very informative to understand relationships between sensors responses and chemical composition of wines. The results obtained indicate that the analytical methods employed are useful tools to follow the wine ageing process, to differentiate wine samples according to ageing type (either in barrel or in stainless steel tanks with the addition of small oak wood pieces) and to the origin (French or American) of the oak wood. Finally, it was possible to designate the volatile compounds which play a major role in such a characterisation.

Analysis of the influence of the type of closure in the organoleptic characteristics of a red wine by using an electronic panel.

An electronic panel formed by an electronic nose, an electronic tongue and an electronic eye has been successfully used to evaluate the organoleptic characteristics of red wines vinified using different extraction techniques and micro-oxygenation methods and bottled using closures of different oxygen transmission rates (OTR). The three systems have demonstrated a good capability of discrimination by means of Principal Component Analysis (PCA). Partial Least Squares Discriminant Analysis (PLS-DA) has permitted to establish prediction models based on the type of closure, the polyphenol content or the effect of micro-oxygenation. The best correlations found using the e-eye and the e-nose are related to the OTR of the closure. In contrast, the electronic tongue is more sensitive to the polyphenol content. The discrimination and prediction capabilities of the system are significantly improved when signals from each module are combined. The electronic panel can be a useful tool for the characterisation and control of oxygen and antioxidant capability of red wines.

Biomimetic biosensor based on lipidic layers containing tyrosinase and lutetium bisphthalocyanine for the detection of antioxidants.

This paper describes the preparation of a biomimetic Langmuir-Blodgett film of tyrosinase incorporated in a lipidic layer and the use of lutetium bisphthalocyanine as an electron mediator for the voltammetric detection of phenol derivatives, which include one monophenol (vanillic acid), two diphenols (catechol and caffeic acid) and two triphenols (gallic acid and pyrogallol). The first redox process of the voltammetric responses is associated with the reduction of the enzymatically formed o-quinone and is favoured by the lutetium bisphthalocyanine because significant signal amplification is observed, while the second is associated with the electrochemical oxidation of the antioxidant and occurs at lower potentials in the presence of an electron mediator. The biosensor shows low detection limit (1.98×10(-6)-27.49×10(-6) M), good reproducibility, and high affinity to antioxidants (K(M) in the range of 62.31-144.87 µM). The excellent functionality of the enzyme obtained using a biomimetic immobilisation method, the selectivity afforded by enzyme catalysis, the signal enhancement caused by the lutetium bisphthalocyanine mediator and the increased selectivity of the curves due to the occurrence of two redox processes make these sensors exceptionally suitable for the detection of phenolic compounds.

Combination of an e-nose, an e-tongue and an e-eye for the characterisation of olive oils with different degree of bitterness.

An electronic panel has been used to characterise the organoleptic characteristics of twenty-five extra virgin olive oils from varieties Hojiblanca, Picual and Arbequina, with different degree of bitterness. The method consists in the combination of three systems: electronic nose, electronic tongue and electronic eye. The Principal Component Analysis (PCA), where PC1, PC2 and PC3 explained 59% of the total variance between the samples, has demonstrated that the capability of discrimination of the combined system is superior to that obtained with the three instruments separately. This improvement is due to the increased information extracted from each sample. Partial Least Squares-Discriminant Analysis (PLS-DA) has allowed separation of the groups in function of olive variety with a root mean square error of prediction (RMSEP) lower than 0.099. Using PLS1 and PLS2 regression models, good correlations have been found between the signals obtained from the electronic tongue and the polyphenolic content (measured by chromatographic methods) or the bitterness index (scored by a panel of experts) with correlation coefficients higher than 0.9 in calibration and validation. These preliminary results indicate that the combination of an e-nose, an e-tongue and an e-eye can be a useful tool for the analysis of olive oil bitterness.

Taking advantage of electrostatic interactions to grow Langmuir-Blodgett films containing multilayers of the phospholipid dipalmitoylphosphatidylglycerol.

The use of phospholipids as mimetic systems for studies involving the cell membrane is a well-known approach. In this context, the Langmuir and Langmuir-Blodgett (LB) methods are among the main techniques used to produce ordered layers of phospholipids structured as mono- or bilayers on water subphase and solid substrates. However, the difficulties of producing multilayer LB films of phospholipids restrict the application of this technique depending on the sensitivity of the experimental analysis to be conducted. Here, an alternative approach is used to produce LB films containing multilayers of the negative phospholipid dipalmitoylphosphatidylglycerol (DPPG). Inspired by the electrostatic layer-by-layer (LbL) technique, DPPG multilayer LB films were produced by transferring the DPPG Langmuir monolayers from the water subphase containing low concentrations of the cationic polyelectrolyte poly(allylamine hydrochloride) (PAH) onto solid substrates. Fourier transform infrared (FTIR) absorption spectroscopy revealed that the interactions between the NH(3)(+) (PAH) and PO(4)(-) (DPPG) groups might be the main driving forces that allow growth of these LB films. Besides, ultraviolet-visible (UV-vis) absorption spectroscopy showed that the multilayer LB films can be grown in a controlled way in terms of thickness at nanometer scale. Cyclic voltammetry showed that DPPG and PAH are more packed in the LB than LbL films. The latter finding is related to the distinct molecular architecture of the films since DPPG is structured as monolayers in the LB films and multilamellar vesicles in the LbL films. Despite the interaction with PAH, cyclic voltammetry also showed that DPPG retains its biological activity in LB films, which is a key factor since this makes DPPG a suitable material in sensing applications. Therefore, multilayer LB films were deposited onto Pt interdigitated electrodes forming sensing units, which were applied in the detection of a phenothiazine compound [methylene blue (MB)] using impedance spectroscopy. The performance of DPPG in single-layer and multilayer LB films was compared to the performance of sensing unities composed of DPPG in single-layer and multilayer LbL films, showing the importance of both the thickness and the molecular architecture of the thin films. As found in a previous work for LbL films, the high sensitivity reached by these sensing units is intimately related to changes in the morphology of the film as evidenced by the micro-Raman technique. Finally, the interaction between MB and the (DPPG+PAH) LB films was complemented by pi-A isotherms and surface-enhanced resonance Raman scattering (SERRS).

Sensors based on double-decker rare earth phthalocyanines.

Phthalocyanines are interesting materials for sensing applications because their physicochemical properties are susceptible to be modified by the presence of certain molecules. Among the large family of the phthalocyanines, the sensing properties of double-decker phthalocyanines (which are sandwich-type complexes where a lanthanide metal is co-ordinated with two phthalocyanine rings) are of special interest due to their unique physicochemical properties. Their high intrinsic semiconductivity and their rich electrochemical and electrochromic behaviour, facilitate enormously the measurement of the changes in the physicochemical properties caused by the environment. In spite of their remarkable sensing behaviour, bisphthalocyanines have not been so extensively studied as sensitive materials as the parent monophthalocyanine compounds. This is due to the difficulty of the synthesis and purification processes, and to the fact that these compounds are not commercially available. In this paper, the sensing devices constructed using rare earth bisphthalocyanines are revised (including sensors foe electronic noses and electronic tongues) and their advantages discussed.

Association of HCV and HBV markers in Spanish HIV-seropositive patients in relation to risk practices.

BACKGROUND/AIMS: HBV, HCV, and HIV have some transmission routes in common. Viral liver disease is a leading cause of mortality in HIV-infected patients. The study was aimed at evaluating the prevalence of HBV and HCV markers in subjects with different risk practices for HIV infection. METHODOLOGY: A total of 699 subjects were studied Of these subjects, 517 were intravenous drug users (373 HIV-positive and 144 HIV-negative), 127 had heterosexual risk practice (66 HIV-positive and 61 HIV-negative), 31 had homosexual risk practice (all HIV-positive), 15 had post-transfusional HIV infection, and nine had HIV infection of unknown source. Patients with anti-HBc antibody were considered HBV-positive, and cases with anti-HCV antibodies were considered HCV-positive. RESULTS: Among patients with HIV infection, most intravenous drug users (79%) had markers of both HBV and HCV, compared with 20%, 11%, and 10% of cases infected by transfusional, heterosexual, and homosexual route, respectively (p < 0.001). Absence of both HBV and HCV markers was observed in most HIV-positive heterosexuals (62%) compared with 40% of post-transfusional cases, 32% of homosexuals and 4% of intravenous drug users (p: NS, p = 0.009, and p < 0.001, respectively). Isolated HBV-positivity was the most frequent pattern in HIV-infected homosexuals (58%), compared with 27% of post-transfusional, 21% of heterosexuals and 11% of intravenous drug users (p: NS, p < 0.001 and p < 0.001, respectively). HIV-negative intravenous drug users had a lower prevalence of HBV/HCV association than HIV-positive cases (p < 0.001). Isolated HCV-positivity was more frequent in HIV-negative than in HIV-positive intravenous drug users (27% vs. 6%, p < 0.001). In heterosexuals, isolated HBV-positivity was more prevalent in HIV-positive than in HIV-negative cases (21% vs. 7%, p = 0.04). CONCLUSIONS: HBV and HCV seroprevalence in HIV infected patients vary depending on the risk practice. This suggests a variable transmissibility depending on the route considered. Within the same risk practice, differences in HCV and HBV seroprevalence between HIV-positive and HIV-negative cases suggest that some factors associated with HIV infection may influence the rate of infection by HCV and HBV.