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Thin-film transistors (TFTs) are a cutting-edge technology for biosensing applications due to their fast response time, low signal-to-noise ratio, and straightforward miniaturization into electronic circuitry. Liquid-gated reduced graphene oxide TFTs (rGO-TFTs) are particularly promising as biosensors since they allow direct coupling between the active material and any (bio-) chemical species dissolved in aqueous solution. In this work, we explore the use of ambipolar rGO-TFTs as transducers for biosensing, focusing on the detection of bacteria proliferation in laboratory-made samples. We choose Lactococcus lactis (L. lactis) as a reference bacterial species due to the potential final applications for the dairy industry. We performed electrical characterization of two different rGO-TFTs based on Si substrate (Si-TFT) and PET substrate (PET-TFT), assessing the devices’ stability, and extrapolating the parameters through a suitable model. The characterization is carried out using M17 broth as the liquid gate. The L. lactis detection is based on the evident parametric shifts of threshold potential caused by the bacterial presence at the liquid gate. The experimental results are compared with optical absorbance measurements at 600 nm to validate the proposed method. Experimental tests with laboratory-made L. lactis samples confirm that PET-TFTs have a higher detection capability compared to Si-TFTs, being also suitable to monitor the bacteria proliferation during observation of 370 min. rGO-TFTs show evident shifts of threshold potential of more than −100 mV in L. lactis spiked M17 broth compared to the pristine one.

The large number of studies involving nanoparticles for cancer therapy is due to their peculiar features: they protect loaded active molecules while extending circulation time and can extravasate from the blood flow to the tumor to deliver drugs directly in the target area. Mathematical modeling can provide a preliminary in silicoexploration of design space to optimize an experimental activity that often relies on a trial-and-error approach. However, because of the characteristic size of these vectors (10–1000 nm), numerous phenomena of interest occur at different time and length scales, making a single modeling technique insufficient to fully characterize the system of interest. In this work we employed a multiscale modeling approach, which bridges the phenomena of interest across different scales, to study the in vitrorelease from polymeric core/shell nanoparticles for cancer therapy loaded with an active compound assembled as a hydrophobic ion pair. The “computational microscope” provided by molecular dynamics simulations was used to track drug molecules through the release process at an atomic scale. The outcomes suggested that the drug is mainly partitioned in the polymer and released as hydrophobic ion pair rather than a free molecule, and that the hydrophobic ion pair is preferentially partitioned in Tween 20 micelles in the release media. A model at macroscale, aimed at describing the release rate and elucidating the release mechanism, was developed according to the results from molecular simulations and validated against experimental data. The outcomes provided insights that are challenging to be obtained experimentally and which supported the development and validation of a release model at macroscale. Overall, the adopted multiscale approach corroborated the experimental findings and provided significant insights into the mechanisms of release.

DAG1encodes for dystroglycan, a key component of the dystrophin-glycoprotein complex (DGC) with a pivotal role in skeletal muscle function and maintenance. Biallelic loss-of-function DAG1variants cause severe muscular dystrophy and muscle-eye-brain disease. A possible contribution of DAG1deficiency to milder muscular phenotypes has been suggested. We investigated the genetic background of twelve subjects with persistent mild-to-severe hyperCKemia to dissect the role of DAG1in this condition. Genetic testing was performed through exome sequencing (ES) or custom NGS panels including various genes involved in a spectrum of muscular disorders. Histopathological and Western blot analyses were performed on muscle biopsy samples obtained from three patients. We identified seven novel heterozygous truncating variants in DAG1segregating with isolated or pauci-symptomatic hyperCKemia in all families. The variants were rare and predicted to lead to nonsense-mediated mRNA decay or the formation of a truncated transcript. In four cases, DAG1variants were inherited from similarly affected parents. Histopathological analysis revealed a decreased expression of dystroglycan subunits and Western blot confirmed a significantly reduced expression of beta-dystroglycan in muscle samples. This study supports the pathogenic role of DAG1haploinsufficiency in isolated or pauci-symptomatic hyperCKemia, with implications for clinical management and genetic counseling.

Purpose: Aims of this study were to investigate the prevalence of TP53and TERTmutations in Medullary Thyroid carcinoma (MTC) and their role in inducing aggressiveness in positive cases. Methods: We performed a literature search in PubMed to identify studies investigating the prevalence of TERTand TP53mutations in MTC. We also included data on MTC cases (n = 193) obtained at our center and unpublished. The in-silico pathogenicity of the TP53mutations has been evaluated by predictor tools. Results: We identified a total of 25 and 11 published papers: all together 1280 cases have been investigated for the presence of TP53mutations and 974 for TERTpromoter mutation. Twenty-five out of 1280 (2%) cases had a TP53mutation while only 3/974 MTC cases (0.3%) have been found to be positive for TERTpromoter mutations. Among all, we identified 19 different TP53 mutations that in 12 cases were demonstrated to have an in silico predicted high pathogenic role and a high impact on protein function. Three non-sense and 4 probably not damaging mutations were also reported. The pathogenic role of the TERTpromoter mutations has been previously in vitro determined. No correlation between TP53and/or TERTmutations and aggressiveness of MTC has been demonstrated. Conclusion: The prevalence of TP53and TERTpromoter mutations is very low in MTC. The reported mutations are pathogenic in the majority of cases. Because of their rarity it is not possible to clarify if they play or not a role in the pathogenesis and/or aggressiveness of this specific thyroid tumor.

A series of synthetic alternating and amphiphilic aromatic amide polymers were synthesized by a step growth polymerization. Alternating meta- and para-linkages were introduced to force the polymer chain into a helical shape in the highly polar solvent water. The polymers were analyzed by 1H NMR spectroscopy and SEC in polar aprotic solvents such as DMSO and DMF. However, the polymers also showed good solubility in water. 1H NMR spectroscopy, small-angle X-ray scattering, and dynamic light scattering provided clear evidence of polymer folding in water but not DMF. We employed parallel tempering metadynamics in the well-tempered ensemble (PTMetaD-WTE) to simulate the free energy surfaces of an analogous model polymer in DMF and water. The simulations gave a molecular model of an unfolded structure in DMF and a helically folded tubular structure in water.

The growth of controlled 1D carbon-based nanostructures on metal surfaces is a multistep process whose path, activation energies, and intermediate metastable states strongly depend on the employed substrate. Whereas this process has been extensively studied on gold, less work has been dedicated to silver surfaces, which have a rather different catalytic activity. In this work, we present an experimental and theoretical investigation of the growth of poly-p-phenylene (PPP) chains and subsequent narrow graphene ribbons starting from 4,4″-dibromo-p-terphenyl molecular precursors deposited at the silver surface. By combing scanning tunneling microscopy (STM) imaging and density functional theory (DFT) simulations, we describe the molecular morphology and organization at different steps of the growth process and we discuss the stability and conversion of the encountered species on the basis of calculated thermodynamic quantities. Unlike the case of gold, at the debromination step we observe the appearance of organometallic molecules and chains, which can be explained by their negative formation energy in the presence of a silver adatom reservoir. At the dehydrogenation temperature, the persistence of intercalated Br atoms hinders the formation of well-structured graphene ribbons, which are instead observed on gold, leading only to a partial lateral coupling of the PPP chains. We numerically derive very different activation energies for Br desorption from the Ag and Au surfaces, thereby confirming the importance of this process in defining the kinetics of the formation of molecular chains and graphene ribbons on different metal surfaces.

ABSTRACTIntroductionLiver involvement in COVID-19 is multifactorial, and the three potential mechanisms are direct hepatocyte viral damage, vascular or cellular damage during the cytokine storm of severe COVID-19 and drug-induced liver injury. To date, three antivirals are licensed for the treatment of COVID-19 by most guidelines: remdesivir, molnupiravir, and ritonavir-boosted nirmatrelvir.Areas coveredWe performed a narrative review about the hepatic safety profile of the three antivirals licensed for COVID-19 treatment. We used data about hepatobiliary adverse events from English-language randomized clinical trials (RCTs).Expert opinionRemdesivir was found to be potentially hepatotoxic, and liver biochemistry abnormalities were common (2–34%) but mild and reversible. Molnupiravir exhibits a favorable safety profile and the increase in aminotransferases was usually mild and reversible (up to 11% of patients in one study). Ritonavir-boosted nirmatrelvir is potentially hepatotoxic, but in the only phase 3 RCT there were no safety issues and aspartate aminotransferase/alanine aminotransferase levels increase did not exceed 2.4% of patients. All antivirals have a favorable safety profile, but they are not sufficiently studied in patients with underlying chronic kidney or liver disease. In this special populations, antivirals should be used with caution and careful monitoring during treatment should be pursued on a case-by-case basis.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies, and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow-up. Early diagnosis and treatment are crucial to avoid central nervous system damage and germ cell tumor dissemination and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with apparently idiopathic CDI is particularly emphasized because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.

Background: Several recent studies suggest that γδ T lymphocytes play an important role in immunity against Mycobacterium tuberculosis. However, the dynamics of these cells in the peripheral blood of patients [...]

High-MgO lamproite and lamproite-like (i.e. lamprophyric) ultrapotassic rocks are recurrent in the Mediterranean and surrounding regions. They are associated in space and time with ultrapotassic shoshonites and high-K calc-alkaline rocks. This magmatism is linked with the geodynamic evolution of the westernmost sector of the Alpine–Himalayan collisional margin, which followed the closure of the Tethys Ocean. Subduction-related lamproites, lamprophyres, shoshonites and high-K calc-alkaline suites were emplaced in the Mediterranean region in the form of shallow level intrusions (e.g. plugs, dykes and laccoliths) and small volume lava flows, with very subordinate pyroclastic rocks, starting from the Oligocene, in the Western Alps (northern Italy), through the Late Miocene in Corsica (southern France) and in Murcia-Almeria (southeastern Spain), to the Plio-Pleistocene in Southern Tuscany and Northern Latium (central Italy), in the Balkan peninsula (Serbia and Macedonia) and in the Western Anatolia (Turkey). The ultrapotassic rocks are mostly lamprophyric, but olivine latitic lavas with a clear lamproitic affinity are also found, as well as dacitic to trachytic differentiated products. Lamproite-like rocks range from slightly silica under-saturated to silica over-saturated composition, have relatively low Al2O3, CaO and Na2O contents, resulting in plagioclase-free parageneses, and consist of abundant K-feldspar, phlogopite, diopsidic clinopyroxene and highly forsteritic olivine. Leucite is generally absent, and it is rarely found only in the groundmasses of Spanish lamproites. Mediterranean lamproites and associated rocks share an extreme enrichment in many incompatible trace elements and depletion in High Field Strength Elements and high, and positively correlated Th/La and Sm/La ratios. They have radiogenic Sr and unradiogenic Nd isotope compositions, high 207Pb over 206Pb and high time-integrated 232Th/238U. Their composition requires an originally depleted lithospheric mantle source metasomatized by at least two different agents: (1) a high Th/La and Sm/La (i.e. SALATHO) component deriving from lawsonite-bearing, ancient crustal domains likely hosted in mélanges formed during the diachronous collision of the northward drifting continental slivers from Gondwana; (2) a K-rich component derived from a recent subduction and recycling of siliciclastic sediments. These metasomatic melts produced a lithospheric mantle source characterized by network of felsic and phlogopite-rich veins, respectively. Geothermal readjustment during post-collisional events induced progressive melting of the different types of veins and the surrounding peridotite generating the entire compositional spectrum of the observed magmas. In this complex scenario, orogenic Mediterranean lamproites represent rocks that characterize areas that were affected by multiple Wilson cycles, as observed in the Alpine–Himalayan Realm.

Mast Cell Hyperplasia and Evidence for Extracellular Release of Tryptase Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by air space inflammation and fibrosis of unknown origin. The pathogenesis of [...]

AbstractThe trophic ecology of Chiloneusweevil species from Sicily was unknown until recently when the host plant of these closely related species was discovered. The opportunity to collect many samples of these elusive species allowed us to re-evaluate the morphology and the genetic relationships among the three closest of the four species inhabiting Sicily and the adjoining islands. We analysed a fragment of the cox1 mitochondrial gene of adult specimens collected from the host plant Drimia pancrationin Sicily, Pantelleria, Pelagie Islands and Malta to study the population structure and the relationships among the different nominal species known so far. Both morphological and genetic results suggest that the previous three species are actually two species with disjunct distribution, for which the new synonymy C. hoffmanni(González, 1970) (= C. solariiPesarini, 1970, syn. nov.) is established. Chiloneus meridionalis(Boheman, 1840) inhabits the main island of Sicily and Pantelleria island, while C. hoffmanniis restricted to Malta and Pelagie islands. Adults of the two species are very similar in general appearance but still distinguishable by a set of well-established characters presented here in a key to their identification. The genetic approach provided evidence of a certain degree of structure of the genetic variation within the two species that would be worth addressing from a phylogeographic perspective in future work.urn:lsid:zoobank.org:pub:1F03BA05-B7A9-44B7-8225-321174A1E3FB

Confinement of liquid crystals (LCs) in polymeric fibers offers a promising strategy to control liquid crystal response to external stimuli. Here, the confinement of 4-cyano-4′-pentylbiphenyl (5CB), a nematic liquid crystal, within the core of coaxially electrospun fibers composed of poly(vinylpyrrolidone) (PVP) containing different surfactants is discussed. The effects of surfactant type, surfactant concentration, and core flow rate (confinement) on the LC behavior were demonstrated using polarized optical microscopy, scanning electron microscopy, differential scanning calorimetry, Raman, and dielectric spectroscopy. Introduction of surfactant dopants of varying hydrophilic and hydrophobic components into the sheath altered the interfacial interaction between the PVP sheath and the 5CB core of the fibers. Significant effects on the LC nematic to isotropic phase transition were attributed to changes in surface anchoring between the sheath and core. Confinement of nematic LCs in surfactant doped polymeric fibers demonstrates a facile method for tuning LC phase behavior.

Conformationally rigid multipodal molecules should control the orientation and packing density of functional head groups upon self-assembly on solid supports. Common tripods frequently fail in this regard because of inhomogeneous bonding configuration and stochastic orientation. These issues are circumvented by a suitable tetrapodal diazatriptycene moiety, bearing four thiol-anchoring groups, as demonstrated in the present study. Such molecules form well-defined self-assembled monolayers (SAMs) on Au(111) substrates, whereby the tetrapodal scaffold enforces a nearly upright orientation of the terminal head group with respect to the substrate, with at least three of the four anchoring groups providing thiolate-like covalent attachment to the surface. Functionalization by condensation chemistry allows a large variety of functional head groups to be introduced to the tetrapod, paving the path toward advanced surface engineering and sensor fabrication.

Byline: Michael Casalini The American banking system needs to get back to its roots as the hub of small-business growth. Lending is down, penalty fees are up, and, as the [...]

Abstract Dynamic relaxation processes are fundamental to understand the mechanical and physical properties of metallic glasses. In the current work, mechanical relaxations in a La 30 Ce 30 Al 15 Co 25 bulk metallic glass were probed by dynamic mechanical analysis. In contrast to many metallic glasses, La 30 Ce 30 Al 15 Co 25 metallic glass shows a pronounced slow β relaxation peak. Physical aging below the glass transition temperature T g leads to an increase of the apparent activation energy and a decrease of the slow β relaxation magnitude. The correlation between the slow β relaxation and the main α relaxation is discussed. [ABSTRACT FROM AUTHOR]

Background: The work presented here is focused on the development of a comprehensive theoretical model for the description of drug release from a double - layer bioresorbable suture thread and the therapeutic efficacy of the active compounds delivered in the surrounding tissue. Methods: In particular, the system under investigation is composed of a core of slow-degrading polylactic- acid-co-ε-caprolactone (PLCL), where an antibiotic compound (Vancomycin) is loaded, surrounded by a shell of a fast-degrading polylactic-co-glycolic acid (PLGA) which contains an anesthetic drug (Lidocaine hydrochloride) for the post-surgical pain relief. Results: This system is of potential interest for the combined effects provided by the different active molecules, but the different release and polymer degradation dynamics, as well as their mutual influence, do not allow an intuitive a priori evaluation of device behavior, which can be rationalized through mathematical modeling. The model takes into account the main involved phenomena (polymer degradation and diffusion of the drugs within the device and the tissue, where they are metabolized) and their synergic effects on the overall system behavior. Conclusion: Model results are discussed in order to quantify the impact of the main design parameters on device performances, thanks to the use of phase diagrams (which show drug effect in time and space) whose insights are summarized in order to determine a design space according to the specific needs.

Background: Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. Goal: To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. Study Design: A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. Results: Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P [is less than] 0.001). Conclusions: For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.

Comparison With Bronchial Wash and BAL Objectives: Sarcoidosis is characterized by a diffuse alveolar inflammatory process, although bronchial airways are often involved. This study compares the cellular profiles of induced [...]

Encapsulation of the nematic liquid crystal N-(4-methoxybenzylidene)-4-butylaniline (MBBA) into the core of poly(vinylpyrrolidone) (PVP) microfibers has been accomplished via coaxial electrospinning for the first time. Data from optical microscopy, two-dimensional Raman mapping, differential scanning calorimetry, and dielectric spectroscopy have been employed to gain detailed insights into the confinement effects on MBBA in a semiflexible polymer sheath. The electrospun fiber diameters could be tuned easily by modifying the flow rate of MBBA, and both the MBBA core and PVP sheath diameters were determined via Raman line cuts. The PVP sheath induced alignment of MBBA, where its long axis is parallel to the fiber axis. Further, the alignment of MBBA led to iridescence in the fibers, which was found to be temperature-sensitive and reversible. Surprisingly, at temperatures below 0 °C, the phase-transition temperatures of confined MBBA are different than the neat and one of its smectic phases is inhibited by the PVP sheath; however, the phases that occur above 0 °C appear to be unrestricted. Thus, electrospun core–sheath fibers with MBBA and PVP provide a useful platform for a semiflexible material, where it is especially necessary to control liquid crystal alignment and polymorphs or phases at low temperature. Overall, the results reported here provide new and important considerations for the effects of confinement on liquid crystals in semiflexible media.

We have previously shown that the d16HER2 splice variant is linked to HER2-positive breast cancer (BC) tumorigenesis, progression and response to Trastuzumab. However, the mechanisms by which d16HER2 contributes to HER2-driven aggressiveness and targeted therapy susceptibility remain uncertain. Here, we report that the d16HER2-positive mammary tumor cell lines MI6 and MI7, derived from spontaneous lesions of d16HER2 transgenic (tg) mice and resembling the aggressive features of primary lesions, are enriched in the expression of Wnt, Notch and epithelial–mesenchymal transition pathways related genes compared with full-length wild-type (WT) HER2-positive cells (WTHER2_1 and WTHER2_2) derived from spontaneous tumors arising in WTHER2 tg mice. MI6 cells exhibited increased resistance to anoikis and significantly higher mammosphere-forming efficiency (MFE) and self-renewal capability than the WTHER2-positive counterpart. Furthermore, d16HER2-positive tumor cells expressed a higher fraction of CD29High/CD24+/SCA1Lowcells and displayed greater in vivo tumor engraftment in serial dilution conditions than WTHER2_1 cells. Accordingly, NOTCH inhibitors impaired mammosphere formation only in MI6 cells. A comparative analysis of stemness-related features driven by d16HER2 and WTHER2 in ad hoc engineered human BC cells (MCF7 and T47D) revealed a higher MFE and aldehyde dehydrogenase-positive staining in d16HER2- vs WTHER2-infected cells, sustaining consistent BC-initiating cell enrichment in the human setting. Moreover, marked CD44 expression was found in MCF7_d16 and T47D_d16 cells vs their WTHER2 and Mock counterparts. Clinically, BC cases from two distinct HER2-positive cohorts characterized by high levels of expression of the activated-d16HER2 metagene were significantly enriched in the Notch family and signal transducer genes vs those with low levels of the metagene.

The active volcano of Ischia, an island off-shore the city of Naples, Southern Italy, has a discontinuous volcanic activity characterized by caldera-forming paroxysmal eruptions, lava flows, and lava domes, and thus offers the opportunity to study the complexity of magma storage, differentiation, and extraction mechanisms in a long-lived magma reservoir. The overall geochemical composition of erupted magmas varies from shoshonite to latite and trachyte/trachyphonolite. Their Sr and Nd, isotope composition variation is typical of subduction-related magmas, akin to other potassic magmas of the Neapolitan District, and there is a complete overlap of radiogenic isotope composition among shoshonite, latite, and trachyte/trachyphonolite. The lack of systematic radiogenic isotope covariation during differentiation suggests that the radiogenic isotope variability could be a signature of each magma pulse that subsequently evolved in a closed-system environment. Erupted magmas record a recurrent evolutionary process consisting of two-step fractional crystallization along similar liquid lines of descent for each magma pulse, suggesting near steady-state magma chamber conditions with balanced alternating periods of replenishment, differentiation, and eruption. The dominant role of fractionating feldspars determines a significant depletion of Sr (<10 ppm) coupled with high Rb/Sr (>200) in the residual trachyte magma.

Because of its complex life cycle and due to multiple stress factors, the European eel is suffering a dramatic decline and has been declared Critically Endangered by the IUCN. A possible way to address this problem could be relieve the pressure on natural stocks by implementing its mass production by artificial breeding protocols. A previous study based on direct observation and parentage assignment underlined the presence of an allegedly hierarchic structure among European eel males in semi-natural mating conditions, with a consequent bias in F1 proportion assigned to each one. The aim of the present study is to attest if a different fertilization protocol based on the artificial mixing of female eggs with different males’ milt in equal volume (1 F:4 M) could represent a solution to the disproportion observed in semi-natural conditions. For this purpose, six families of European eels were generated, and 10 species-specific microsatellite loci were used to infer offspring composition by paternity assignment on 280 samples. Due to the asynchronous ovarian development of female European eels, the percentage of fertilized eggs for each female showed a great variability, ranging from 4.70% to 94.50%. A proportion of 94.02% of genotyped offspring were assigned with high confidence to their true parents. As regard males’ fertilization pattern, no substantial differences from natural mating were observed: a single male accounted for most offspring, which was just mostly composed of full sibs. Concluding, the obtained results suggest that the admixture of an equal volume of different males’ milt seems to contribute to the single-locus genetic variability (observed heterozygosity higher than expected in 7 out 9 loci), but it is not sufficient to ensure all the males the same chance to transmit their gene pool, and new fertilization strategies must be developed.

Dissolution of ionizable drugs and their salts is a function of drug surface solubility driven by the surface pH, i.e., the microenvironmental pH at the solid/liquid interface, which will deviate from bulk pH when there is an acid–base reaction occurring at the solid/liquid interface. In this work, we first present a brief overview of the modeling approaches available in the literature, classified according to the rate-determining step assumed in the dissolution process. In the second part, we present and evaluate the prediction performance of two different modeling approaches for surface pH. The first method relies only on thermodynamic equilibria, while the second method accounts for transport phenomena of charged compounds through the diffusional boundary layer using the Nernst – Planck equation. Model outcomes are compared with experimental data taken from the literature and obtained during this work. In terms of surface pH predictions, the models provide identical values for weak acids or weak bases. The models’ outcomes for bases are in good agreement with experimental data in acidic conditions (bulk pH 1–4), while overpredictions are observed in the 5–7 bulk pH range in a system-dependent manner. Deviations can be related to the effect of surface dissolution (also referred to as surface reaction), which may become a controlling mechanism and slow the replenishment of the unionized drug at the surface of the crystal. Surface pH predictions for acids are generally in good agreement with experiments, with a slight underestimation for some drug examples, which could be related to errors in intrinsic solubility determination or to the assumption of thermodynamic equilibrium at the surface of the drug. A good agreement is also observed for salts with the thermodynamic model except for mesylate salts, suggesting that other phenomena, not currently included in the thermodynamic equilibrium model, may determine the surface pH.

Byline: Antonio Corno, Michele Samaja, Stefania Casalini, Sonia Allibardi Author Affiliation: Milan, Italy Article Note: (footnote) [star] From Hospital 'S. Donato,' a University of Milan,b and Scientific Institute 'S. Raffaele,' c Milan, Italy., [star][star] J THORAC CARDIOVASC SURG 1995;109:1250-1, a 0022-5223/95 $3.00 + 0, aa 12/8/59359

Electrolyte-gated organic field-effect transistors (EGOFETs), based on ultrathin pentacene films on quartz, were operated with electrolyte solutions whose pH was systematically changed. Transistor parameters exhibit nonmonotonic variation versus pH, which cannot be accounted for by capacitive coupling through the Debye–Helmholtz layer. The data were fitted with an analytical model of the accumulated charge in the EGOFET, where Langmuir adsorption was introduced to describe the pH-dependent charge buildup at the quartz surface. The model provides an excellent fit to the threshold voltage and transfer characteristics as a function of the pH, which demonstrates that quartz acts as a second gate controlled by pH and is mostly effective from neutral to alkaline pH. The effective capacitance of the device is always greater than the capacitance of the electrolyte, thus highlighting the role of the substrate as an important active element for amplification of the transistor response.

L’évaluation des pratiques professionnelles (EPP) est définie comme « l’analyse de la pratique professionnelle en référence à des recommandations et selon une méthode élaborée ou validée par la Haute Autorité de santé et inclut la mise en œuvre et le suivi d’actions d’amélioration de la pratique ». L’utilisation d’une recommandation de bonne pratique portant sur la douleur chronique peut être déclinée selon les différentes méthodologies disponibles : l’audit clinique ciblé, la revue de morbi-mortalité, la revue de pertinence, l’élaboration d’une réunion de concertation pluridisciplinaire ou d’un chemin clinique. Elle permet ainsi d’allier la clinique à la démarche qualité de façon ludique. Cet article a pour objectif de vous proposer une boite à outils afin de faire votre EPP sur le domaine de la douleur chronique à partir des recommandations de bonne pratique. De quoi vous aider pour la nouvelle certification de votre établissement !

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Antibody–antigen (Ab–Ag) recognition is the primary event at the basis of many biosensing platforms. In label-free biosensors, these events occurring at solid–liquid interfaces are complex and often difficult to control technologically across the smallest length scales down to the molecular scale. Here a molecular-scale technique, such as single-molecule force spectroscopy, is performed across areas of a real electrode functionalized for the immunodetection of an inflammatory cytokine, viz. interleukin-4 (IL4). The statistical analysis of force–distance curves allows us to quantify the probability, the characteristic length scales, the adhesion energy, and the time scales of specific recognition. These results enable us to rationalize the response of an electrolyte-gated organic field-effect transistor (EGOFET) operated as an IL4 immunosensor. Two different strategies for the immobilization of IL4 antibodies on the Au gate electrode have been compared: antibodies are bound to (i) a smooth film of His-tagged protein G (PG)/Au; (ii) a 6-aminohexanethiol (HSC6NH2) self-assembled monolayer on Au through glutaraldehyde. The most sensitive EGOFET (concentration minimum detection level down to 5 nM of IL4) is obtained with the first functionalization strategy. This result is correlated to the highest probability (30%) of specific binding events detected by force spectroscopy on Ab/PG/Au electrodes, compared to 10% probability on electrodes with the second functionalization. Specifically, this demonstrates that Ab/PG/Au yields the largest areal density of oriented antibodies available for recognition. More in general, this work shows that specific recognition events in multiscale biosensors can be assessed, quantified, and optimized by means of a nanoscale technique.

Four linear terarylene molecules (i) 4-nitro-terphenyl-4″-methanethiol (NTM), (ii) 4-nitro-terphenyl-3″,5″-dimethanethiol (NTD), (iii) ([1,1′;4′,1″] terphenyl-3,5-diyl)methanethiol (TM), and (iv) ([1,1′;4′,1″] terphenyl-3,5-diyl)dimethanethiol (TD) have been synthesized and their self-assembled monolayers (SAMs) have been obtained on polycrystalline gold. NTM and NTD SAMs have been characterized by X-ray photoelectron spectroscopy, Kelvin probe measurements, electrochemistry, and contact angle measurements. The terminal nitro group (−NO2) is irreversibly reduced to hydroxylamine (−NHOH), which can be reversibly turned into nitroso group (−NO). The direct comparison between NTM/NTD and TM/TD SAMs unambiguously shows the crucial influence of the nitro group on electrowetting properties of polycrystalline Au. The higher grade of surface tension related to NHOH has been successfully exploited for basic operations of digital μ-fluidics, such as droplets motion and merging.

The present work is focused on the development and the validation of a mechanistic model describing the degradation of drug-loaded polylactic-co-glycolic acid microparticles and the drug release process from such devices. Microparticles’ degradation is described through mass conservation equations; the application of population balances allows a detailed description of the hydrolysis kinetics, which also takes into account the autocatalytic behavior that characterizes bulk eroding polymers. Drug release considers both drug dissolution and the diffusion of dissolved active principle through the polymeric matrix. The diffusion of oligomers, water, and drug is assumed to follow Fickian behavior; the use of effective diffusion coefficients takes into account the diffusivity increase due to polymer hydrolysis. The model leads to a system of partial differential equations, solved by means of the method of lines. The model predictions satisfactorily match with different sets of literature data, indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing the device behavior.

We describe the case of a newborn presenting with multicystic encephalomalacy, hydrocephalus and bilateral hemovitreous. An underlying coagulation disorder was suspected and laboratory tests revealed severe protein C deficiency. At 25 days of life, after the appearance of purpura fulminans, replacement therapy with intravenous protein C concentrate (Ceprotin; Baxter, Vienna, Austria) was started.

The morphology, relaxation properties, and conductivity of the statistical copolymer polystyrenic (alkoxy 1H-tetrazole-co-alkoxy nitrile), an anhydrous proton conductor, were measured. The material phase-separates into hard and soft domains, the latter corresponding to a phase richer in the pendant tetrazole groups. Using dielectric and mechanical spectroscopies, two relaxation processes were observed, the slower associated with local segmental dynamics of the backbone and the higher-frequency process involving motion of the tetrazole moieties. The latter is coupled to the ionic conductivity, which means that below the principal glass transition of the material (∼313 K) the conductive mechanism remains active. Thus, the usual compromise in proton exchange membranes between mechanical stability and ion conductivity can be avoided.

To compare pre and post-ART attrition between youth (15–24 years) and other patients in HIV care, and to investigate factors associated with attrition among youth.

AbstractLung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

Foreign body (FB) inhalation is a potentially life-threatening emergency also in clinically stable patients as the situation could worsen at any moment. There is varying opinion regarding the urgency for removal of inhaled FBs, and there are no guidelines in the literature. The aim of our study was to present our experience with FB aspiration in children and adults from 1993, when we introduced our Thoracic Endoscopy Service with the availability “on call” of a bronchologist 24 hours a day, 7 days a week, defining a dedicated protocol together with our anaesthesiologists for prompt intervention in this situation.

An investigation of the recombination kinetics and the density of states distribution in bulk heterojunction organic photovoltaic cells was undertaken using impedance spectroscopy measurements under varying levels of illuminations. Three organic polymer solar cells were investigated which differed only by the p-type polymer used in the active layers while the device architecture and acceptor molecule (PC70BM) were kept the same. We found that the density of states profiles for the three cells are similar and can be superimposed by a horizontal shift due to a difference between the polymers’ HOMO and the PC70BM’s LUMO levels. The recombination mechanisms for the three cells showed the same behavior, suggesting an important role of the acceptor in this process; however, large differences in the absolute value of carrier lifetime τeffrelated to the choice of the polymer are evident, indicating that the recombination kinetics depends on a combination of the properties of both materials and the morphology of their blend.