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Objective To characterize a cohort of patients with SCN8A-related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills. Methods We analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children with SCN8A variants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the Denver II items. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression. Results The 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant in SCN8A and those with an additional variant reported in a gene other than SCN8A, as well as between patients with different patterns of regression before and at seizure onset. Significance This is the first study of an SCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children with SCN8A-related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures for SCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.

Variants implicated in childhood epilepsy have been identified in all four voltage-gated sodium channels that initiate action potentials in the central nervous system. Previous research has focused on the functional effects of particular variants within the most studied of these channels (NaV1.1, NaV1.2 and NaV1.6); however, there have been few comparative studies across channels to infer the impact of mutations in patients with epilepsy. Here we compare patterns of variation in patient and public databases to test the hypothesis that regions of known functional significance within voltage-gated sodium (NaV) channels have an increased burden of deleterious variants. We assessed mutational burden in different regions of the Nav channels by (1) performing Fisher exact tests on odds ratios to infer excess variants in domains, segments, and loops of each channel in patient databases versus public "control" databases, and (2) comparing the cumulative distribution of variant sites along DNA sequences of each gene in patient and public databases (i.e., independent of protein structure). Patient variant density was concordant among channels in regions known to play a role in channel function, with statistically significant higher patient variant density in S4-S6 and DIII-DIV and an excess of public variants in SI-S3, DI-DII, DII-DIII. On the other hand, channel-specific patterns of patient burden were found in the NaV1.6 inactivation gate and NaV1.1 S5-S6 linkers, while NaV1.2 and NaV1.6 S4-S5 linkers and S5 segments shared patient variant patterns that contrasted with those in NaV1.1. These different patterns may reflect different roles played by the NaV1.6 inactivation gate in action potential propagation, and by NaV1.1 S5-S6 linkers in loss of function and haploinsufficiency. Interestingly, NaV1.2 and NaV1.6 both lack amino acid substitutions over significantly long stretches in both the patient and public databases suggesting that new mutations in these regions may cause embryonic lethality or a non-epileptic disease phenotype.

This paper presents the selective adsorption of bromine-metallic complexes of Au and Ag on composite membranes, as well as the desorption process and redoping of the conducting polymers. The polyaniline (PANI) and polypyrrole (PPy) membranes exhibited relevant adsorption properties. 72% for gold and 98% for silver with PANI, 50% for gold and 97% for silver with PPy, in bromine complexes. The adsorption capabilities of the composite membranes were attributed to the ion exchange between the dopant and the AuBr 4 − or AgBr 2 − complexes. Both materials fitted to a Langmuir isotherm. PANI-based membranes reached 31.4% of gold and 54.4% of silver desorption whereas PPy-based membranes reached 54% of gold and 28.8% of silver. Redoping studies suggested the potential reuse of the PANI-based membranes at least for six cycles of the adsorption/desorption process. The preparation of cellulose acetate membranes modified with poly (acrylic acid) and triphenyl phosphate and coated with the conducting polymers, PANI or PPy was in accordance to our previously reported method. The composite membranes were characterized by FT-IR, scanning electron microscopy, electrical conductivity measurements, I–V, mechanical tests, contact angle measurements, XRD and energy disperse spectroscopy. The novelty of the present work is the combination of electroconductive polymers, for the recovery of metals, and bromide as a leachate, less harmful than the traditionally used leachers.

Objective: Pathogenic variants in SCN 8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS ) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID ) or movement disorders without epilepsy have been reported. The vast majority of the published SCN 8A patients suffer from severe developmental and epileptic encephalopathy (DEE ). In this study, we aimed to provide further insight on the spectrum of milder SCN 8A‐related epilepsies. Methods: A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. Results: We found 36 probands who presented with an SCN 8A‐related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure‐free, two‐thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. Significance: With this study, we explore the electroclinical features of an intermediate SCN 8A‐related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

Pecan nutshells are a solid form of waste obtained from the pecan nut production and they have been explored as an inexpensive filler for incorporation by melt blending into the poly(lactic acid) (PLA) matrix. The pecan nutshells contain polyphenols, proteins, tannins, sugars, and lipids; some of these components must be released in order to improve adhesion with a polymeric matrix. The physicochemical characterization of the extruded biocomposites of pecan nutshell powder (PNSP) at 0, 5, and 7.5% wt. with two treatments (untreated and defatted) into PLA is presented in this work. The incorporation of PNSP into the PLA matrix caused a variation in color and density and increased the water absorption. However, some mechanical and thermal parameters of the biocomposites showed a significant decrease. The morphological analysis showed good dispersion and adhesion of the PNSP to the PLA matrix. Based on the results of the characterization, biocomposites formulated with defatted PNSP have a potential to be used as sustainable fillers in PLA biocomposites. These biocomposites have a potential application as food containers, packaging trays, or disposable items.

We report, for the first time, the use of a bile salt, the sodium taurocholate (Tch), as a surface-active agent in the emulsion synthesis of electroactive polypyrrole (PPy) nanoparticles. PPy was obtained under mild and environmentally friendly conditions, using hydrogen peroxide (H2O2) as a green oxidant. The combined addition of a non-ionic surfactant, Tween 20 (Tw), was also studied. The electrical, structural, morphological, and colloidal properties of reaction products were analyzed in detail to find the best conditions of synthesis. The pre-polymerization emulsion systems were studied by osmometric measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). A consistent mechanism of nucleation and growth of PPy colloids is proposed. The Tch acts as an emulsifier of the reaction media, a doping agent of oxidized chain of PPy, and a stabilizer of the resulting colloids. The main advantage of this work is the preparation of polymer colloids through a completely green alternative route, which could open up new possibilities for obtaining nanoparticles through an effective and non-toxic method.

Aim Rotator cuff repairs have shown a high level of re-ruptures. We hypothesized that the use of adipose-derived stem cells (ASC) could improve the biomechanical and histological properties of the repair. Materials and methods Controlled experimental study conducted on 44 BDIX rats with section and repair of the supraspinatus tendon and randomization to one of three groups: group A, no intervention (control); group B, local applications of a fibrin sealant; and group C, application of the fibrin sealant with 2 × 106 ASC. At 4 and 8 weeks a biomechanical and histological analysis was performed. Results There were no differences in load-to-failure at 4 and 8 weeks between groups. The load-to-failure did increase between week 4 and week 8. Histologically the tendon-to bone union showed a disorganized fibrovascular tissue. Group C showed a different inflammatory pattern, with less presence of neutrophils and more presence of plasma cells. Conclusion The use of ASC does not improve the biomechanical or histological properties of the repair site. More studies are needed to improve techniques that enhance the healing site of the repair.

Resumen Objetivo La reparacion del manguito rotador tiene una alta tasa de fracaso. Se investiga si la aplicacion de celulas troncales derivadas de lipoaspirado mejorara la resistencia de la reparacion y recreara la entesis original. Material y metodos Estudio experimental en 44 ratas BDIX con seccion y reparacion con sutura del tendon supraespinoso y asignacion aleatoria a uno de 3 grupos: grupo A, nada (control); grupo B, aplicacion local de vehiculo de fibrina; y grupo C, aplicacion de 2 x 106 celulas troncales derivadas de lipoaspirado. Se realiza estudio mecanico en celula de carga y estudio histologico en hematoxilina-eosina. Resultados En el estudio mecanico no hubo diferencias entre grupos. La carga hasta el fracaso aumento de los grupos de 4-8 semanas. En el estudio histologico se observo la union hueso-tendon mediante un tejido fibrovascular desorganizado. En el grupo C se observo un aumento de celulas plasmaticas a las 4 y 8 semanas. Conclusion La utilizacion de celulas troncales derivadas de lipoaspirado no recrea la organizacion celular de la entesis ni mejoran las propiedades biomecanicas de la misma. Son necesarios mas estudios para investigar tecnicas que mejoren la cicatrizacion del tendon.

Investigators from the University of British Columbia, Great Ormond Street Hospital for Children, and the National Hospital reported their findings on neurotransmitter deficiencies in two patients with mutations in voltage-gated sodium genes (SCN2A and SCN8A) discovered by whole exome sequencing.

Diffuse osteosclerotic lesions are a very uncommon radiologic presentation in multiple myeloma. These lesions affect the axial skeleton and proximal limbs; they may be accompanied by osteolytic lesions in the course of the disease. In fact, in cases of diffuse osteosclerosis, the diagnosis of multiple myeloma is reached only after ruling out other, more common diseases. We present an exceptional case of multiple myeloma with diffuse osteosclerosis and highlight the differences between this entity and POEMS syndrome.

The electrical, mechanical, and piezoresistive properties of ternary composites based on elastomeric polydimethylsiloxane (PDMS), carbon nanotubes (CNTs), and polyaniline (PANI) were studied and compared with those of binary PDMS–CNT composites. The presence of PANI affected the percolating network of the CNTs. At lower PANI concentrations (2.5 and 5%), the conductive network of the CNTs was constructively modified; this led to an enhancement in the conductivity in the sample containing 2% CNTs. A higher PANI content (7.5%) hindered the flow of main charge carriers through the composite. The piezoresistive response of the binary and ternary composites was studied by cyclic experiments under compression loads. In all of the samples, the electrical resistance increased monotonically up to a 10% strain. The reproducibility of the piezoresistive behavior in the binary and ternary composites provided evidence that the fillers could reversibly recover their initial position together with the PDMS chains without a significant displacement with respect to their original positions. The reduction of the piezoresistive sensibility by PANI addition was attributed to the displacement restrictions of the CNTs within the composite under pressure because of the volume exclusion of PANI particles; this maintained the probability of CNT contact and increased the possibility of the formation of new CNT conductive channels. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44780.

The purpose of this study was to evaluate the poly-axial locked plating system inserted through a minimally invasive approach for the treatment of three-part fractures of the proximal humerus. Twenty-three patients with a three-part fracture of the proximal humerus treated with a poly-axial locking plate through a percutaneous approach were available for clinical and radiological analysis at a minimum of 2 years follow up (average 36 months; range, 24-54 months). To assess objective and subjective outcomes the Constant Score (CS) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were obtained. All complications were recorded. There were 17 women and 6 men, with a mean age of 62 years (range, 18-86). All fractures healed. At final follow up, the mean forward flexion, external rotation and internal rotation were 126°, 44° and L1, respectively; the mean CS was 64 and the mean DASH score was 23. Twelve patients (52%) had a postoperative complication, which included screw cut-out, stiffness and infection. The poly-axial locked plating system through a minimally-invasive approach may be an appropriate treatment for three-part fractures of the proximal humerus and may reduce the biological aggression of conventional plate fixation.

Aortic aneurysm is predominantly found in the ascending aorta in patients with Marfan syndrome (MFS). However, descending aortic disease has emerged as a problem since people are living longer because of improved medical and surgical management of the ascending aorta. Diagnostic procedures before disease onset and the mechanisms involved in the transition of normal aortic tissue to aneurysm remain unclear. We determined signs of descending aortic disease before disease onset in mice with a mutation in the fibrillin 1 gene (Fbn1 +/C1039G), a validated mouse model of disease susceptibility and progression of aortic aneurysm of MFS. We analyzed a tubular unfixed non-aneurysmal descending thoracic aorta from 8-month-old wild-type and Fbn1 +/C1039G mice by a tubular biaxial tester that works in conjunction with a two-photon nonlinear microscope. Fbn1 +/C1039G mouse aorta was more compliant in the circumferential direction. Two-photon imaging showed defective organization of adventitial collagen fibers in the pressurized aortas of Fbn1 +/C1039G mice. Moreover, disruption in the elastic lamina was noted in the absence of aneurysms in pressurized aortas but not unpressurized aortas of Fbn1 +/C1039G mice. At the molecular level, this altered tissue behavior in non-aneurysmal descending aortas of Fbn1 +/C1039G mice was accompanied by an increasing trend of canonical but not noncanonical, transforming growth factor-β (TGFβ) signaling. Finally, assays of in vitro collagen lattice formation in mouse wild-type and TGFβ1-deficient embryonic fibroblasts indicate that TGFβ1 can regulate collagen organization. The ability to reveal the presence of altered biomechanics and microstructure coupled with subtle changes in TGFβ signaling provides a novel surrogate measure of tissue susceptibility to aneurysm before disease onset.

Composites that incorporate an electrically conducting filler, the hydrochloric polyaniline (PANI-Cl), into hydroxy-terminated polydimethylsiloxane (HO-PDMS) matrix were evaluated for DC electrical, mechanical, thermal, morphological and piezo-resistive properties. The main focus of the study was on the electrical–mechanical behavior of these composites in view of possible piezo-resistive sensor application. The percolation threshold of conductivity was determined to be around 11.5 wt% of PANI-Cl. Compression/expansion cyclic experiments showed that the filler content modified the stiffness, the magnitude of Mullins effect and the hysteresis behavior in elastomeric composites. The piezo-resistive response of composites differed depending on the sample composition and also, on the strain rate. Composites with concentration above the percolation threshold exhibited at least three-order change of its electrical resistance in a narrow interval of maximum 2% of deformation. The piezo-resistive sensitivity and the reproducibility of response suggested the possibility to use this material as a transducer in an electromechanical device.

Cellulose acetate membranes (M1) with controlled thickness were coated with an electroconductive polymer, and the resulting composites were characterized by SEM, XPS, electrical conductivity, and mechanical measurements. A comparative study of M1 coated with polyaniline (PANI) or with polypyrrole (PPy) for adsorption and subsequent desorption of a gold–iodide complex was performed. The PANI-coated M1 (M2) and that coated with PPy (M3) are effective adsorbents for recovery of the AuI2− complex. The adsorption of gold on the membranes was attributed to the exchange between the dopant ions and the AuI2− complex ions. The adsorption equilibrium data fitted the Langmuir isotherm model for both membranes M2 and M3. The desorption of the AuI2− complex with a NH4OH solution 3 M reached 97% for M3 membrane. This study shows a convenient method for the recovery of gold through the use of a complex with iodine without cyanide solutions.

The adsorption of AuIcomplex onto acetate cellulose-polyaniline membranes was investigated. Kinetic experiments showed a rapid adsorption of this complex, which was attributed to an ion-exchange mechanism. Equi- librium adsorption results were represented by the Langmuir model, showing a correlation coefficient of 0.9852. Langmuir parameters K and Qm were found to be 0.2937 L mg � 1 and 1.2394 mg g � 1 , respectively. Approximately 94% of AuI � was adsorbed when a solid/liquid ratio of 40 g L � 1 (grams of membrane/ liter of solution) was used. V C 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 2670-2674, 2009

Four lots of cellulose acetate (CA) membranes, modified with polyacrylic acid, using various plasticizers, and coated with polyaniline (PANI) were prepared. The morphology of the membranes was evaluated by using scanning electron microscopy, and the membranes showed larger pore size when the plasticizers were used. The electrical conductivity of the modified membranes and coated with PANI increased by two orders of magnitude when the plasticizer triphenyl phosphate was used. The strain at break improved by an order of magnitude and the glass transition temperature (Tg) showed an average decrease of 36°C when the membranes were plasticized. Finally, these membranes were tested as ion-exchange materials of a gold-iodide complex. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Seaweed waste (SWW) is a residue or by-product from the filtration step of the agar extraction process, and it has been explored as an inexpensive and effective filler for incorporation by melt blending into a poly(lactic acid) (PLA) matrix. PLA-SWW biocomposites were manufactured with various contents of SWW (0, 5, 10, 15, and 20 wt %) using a sheet extrusion process. PLA was functionalized with maleic anhydride (MAH) by reactive extrusion using dicumyl peroxide (DCP) as an initiator, and it was extruded using 0, 5, and 20 wt %. SWW content. The mechanical, thermal, structural, and morphological properties of the processed biocomposites were investigated. Regarding the mechanical behavior, a slight increase in the tensile modulus was observed at low SWW content. The thermal properties indicated that the rigid amorphous phase content was enhanced in the biocomposites. This work suggests that SWW can be used as filler to develop environmental friendly biocomposites. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42320.

(2006). Triboluminescence of Poly(n-Butyl Methacrylate)- Polyaniline composites. Materials Research Innovations: Vol. 10, No. 2, pp. 262-267.

Poly(n-butyl methacrylate) (PBMA)–polyaniline (PANI) composite films were obtained by extrusion by use of two methods: the first method consisted of polymerizing a thin layer of PANI, with Cl− as dopant, on the extruded film of PBMA; the second method was based on blends of PBMA and PANI produced by the extrusion of the two polymers by using dodecylbenzene sulfonic acid (DBSA) as dopant. The thermal properties, electrical conductivity, and morphology of the composite films obtained were measured. The sensitivity of the composites films as detectors of hydrogen peroxide and ammonia was evaluated. The change in the electrical resistance on exposure to different aqueous solutions of these components shows a linear behavior. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 179–183, 2003

Polyaniline–poly( n -butyl methacrylate) (PAn–PBMA) composite films were obtained by casting. The homogeneous films were prepared with poly(vinyl methyl ether) (PVME) and poly(vinyl ethyl ether) (PVEE) as dispersants, and the electric conductivity, mechanical properties and morphology were studied. The PAn integration to the composite is better when PVEE is used as dispersant, but the conductivity is higher when PVME is used. The composites with PVME were tested as chemical sensors for H 2 O 2 and NH 3 , showing good performance. These samples were also tested as biosensor for urea and uric acid using urease and uricase enzymes, respectively. The best results were as chemical sensor for H 2 O 2 , NH 3 , and as biosensors for serum urea determination.

Impacted morcellised bone allograft and a Charnley stem was used to revise 59 loose femoral components in 57 consecutive patients. Femoral bone loss was rated as Endo-Klinik grade 2 in nine patients, grade 3 in 41, and grade 4 in nine. The immediate postoperative radiographs and those taken at the most recent follow-up were compared for radiolucencies, subsidence and incorporation of the graft. One patient was lost to follow-up and two were not available for radiological analysis. The mean clinical follow-up in 58 procedures was 56.7 months (24 to 144) and the mean radiological review of 56 reconstructions was 54.4 months (24 to 144). An intraoperative femoral fracture occurred in one patient (1.7%) and was successfully treated by strut grafting and cerclage wiring. Extrusion of cement through perforations or incomplete hoop fractures was detected in the postoperative radiographs of ten procedures (17%); none of these patients sustained a complete fracture. Three patients had dislocations (5%) and two (3.5%) developed painful subsidence of the stem which required a further revision. The latest follow-up radiographs in 56 reconstructions showed a well fixed stem and radiological healing of the graft in 52 (93%), and definite loosening in four (7%). Of these four, two were revised again and two were asymptomatic after a follow-up of 120 months each. The mean subsidence in the 52 successful revisions was 0.38 mm (0 to 4). Impaction allografting with a Charnley stem restored bone stock and provided adequate fixation of the stem in 93% of the hips. There was a low rate of rerevision (3.5%) and a low incidence of intraoperative and postoperative complications.

Polypyrrole (PPy) was chemically prepared from aqueous solutions individually containing l-serine or l-glutamic acid, with the addition of ammonium persulfate as the oxidant. The electrical, XPS and FTIR characterizations indicated that the amino acids co-doped the PPy backbone. TEM revealed that PPy presented a quasi-spherical morphology with diameters in nanometric scale. The nanostructures of PPy-glutamic acid efficiently adsorbed therapeutic doses of amoxicillin. Composite hydrogels were obtained by the entrapment of amoxicillin-loaded PPy in polyacrylamide network. The antibiotic molecules can be subsequently released (or sustained) from composite hydrogel in response to application (or removal) of electrical stimulation. This tuning release profile can lead to promising drug delivery applications such as implantable devices and iontophoretic systems. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41804.

Rotator cuff repairs have shown a high level of re-ruptures. We hypothesized that the use of adipose-derived stem cells (ASC) could improve the biomechanical and histological properties of the repair.Controlled experimental study conducted on 44 BDIX rats with section and repair of the supraspinatus tendon and randomization to one of three groups: group A, no intervention (control); group B, local applications of a fibrin sealant; and group C, application of the fibrin sealant with 2 x 10(6) ASC. At 4 and 8 weeks a biomechanical and histological analysis was performed.There were no differences in load-to-failure at 4 and 8 weeks between groups. The load-to-failure did increase between week 4 and week 8. Histologically the tendon-to bone union showed a disorganized fibrovascular tissue. Group C showed a different inflammatory pattern, with less presence of neutrophils and more presence of plasma cells.The use of ASC does not improve the biomechanical or histological properties of the repair site. More studies are needed to improve techniques that enhance the healing site of the repair.

The vitamin D receptor (VDR) stimulates transcription as a 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-activated heterodimer with retinoid X receptor (RXR). RXR also forms homodimers to mediate 9-cis retinoic acid (9-cis RA)-induced gene expression. Both receptors possess a C-terminal hormone-dependent activation function-2 (AF-2), a highly conserved region that binds coactivators to transduce the transcriptional signal. By replacing single amino acids within the AF-2 of human RXR alpha (hRXR alpha) or mouse RXR beta (mRXR beta), the contribution of these residues to transactivation by the RXR-VDR heterodimer and the RXR-RXR homodimer was evaluated. In 9-cis RA-responsive homodimers, the second and fourth positions of the AF-2 (leucine and glutamate respectively) are essential. However, in the context of an RXR-VDR heterodimer activated by 1,25(OH)(2)D(3), alteration of these two RXR residues has little effect. Instead, AF-2 residues located towards the C-terminus, such as the penultimate position (L455 in hRXR alpha or L441 in mRXR beta), are crucial for RXR-VDR heterodimers. Indeed, L455A mutant RXR exerts a dominant negative effect on RXR-VDR transcriptional responsiveness to 1,25(OH)(2)D(3). Further experiments with a mutant hRXR alpha (F313A) which elicits 9-cis RA-independent transactivation as a homodimer demonstrate that, when heterodimerized with VDR, this RXR mutant is incapable of activating the RXR-VDR heterocomplex in the absence of the VDR ligand. Taken together, these results indicate that RXR is a subordinate, yet essential transcriptional partner in RXR-VDR-mediated activation of gene expression. Furthermore, a functional switch in RXR AF-2 signaling occurs between RXR residues in the homodimeric versus the heterodimeric states, likely reflecting different interactions between subregions of the AF-2 and coactivator(s).

Polypyrrole–thermoplastic composite films were obtained by casting. Homogeneous films were prepared with dispersant poly(vinyl methyl ether) or poly(vinyl ethyl ether) by two methods. Electric conductivity, morphology, mechanical properties, and sensitivity to H2O2 in water were studied. Composites of polypyrrole with poly(vinyl chloride) carboxylated and poly(vinyl methyl ether) presented improved mechanical and electrical properties compared with other composites studied. These films were sensitive to H2O2 in water, showing a significant change in electric resistance. This change is discussed in relation to the H2O2 concentration and the exposure time. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1498–1506, 2001

This paper presents a novel biosensing platform for cholesterol accomplished by the spin-coating deposition of neutral polyaniline on poly(methyl methacrylate) support and the subsequent covalent immobilization of cholesterol oxidase onto polyaniline surface. The polyaniline film entraps the enzyme and it also acts as an active layer for optical sensing of free cholesterol. The effects of immobilization process of the enzyme over the oxidation state of polyaniline backbone and the optimum pH and temperature conditions for immobilized cholesterol oxidase were studied. The sensibility of the system to cholesterol in concentrations equivalent to those present in human serum evidences its potentiality in an optical method simply based on chemochromic properties of polyaniline.

Background A lack of adherence to disease modifying antirheumatic drugs (DMARDs) can increase inflammatory activity (IA) in patients with rheumatoid arthritis (RA). Purpose To estimate adherence to subcutaneous biological (DMARD-b) and conventional (DMARD-c) DMARDs in RA patients. To evaluate IA as a function of DMARD adherence. Material and methods Cross sectional study in pharmaceutical care outpatients with RA receiving DMARD-b at a 550 bed hospital in April 2015. Study variables: age, sex, DMARDs, adherence and IA. Adherence was evaluated by two indirect methods: (1) patient self-administered questionnaire (CQR5-Compliance Questionnaire Rheumatology); and (2) electronic dispensation records, calculating the ‘medication possession rate’ (MPR), defined as the number of days a medication was dispensed divided by the number of days of the treatment period during the previous 12 months. ‘Adherent’ patients were defined by MPR ≥80% and CQR5 classification of ‘high adherence’. DAS28 was used to evaluate IA as in remission (DAS28 ≤2.6), low (DAS28 ≤3.2) or moderate (DAS28 >3.2). Data were obtained from: electronic clinical records, community pharmacy electronic prescription dispensing programmes (specialists and community physicians), outpatient dispensing records and pharmaceutical interview. Statistical analysis: Pearson’s χ 2 test was used to compare IA between adherence and non-adherence groups to combination therapy with DMARD-b and DMARD-c. . Results The study included 55 patients (81.8% females, mean age 56 ± 14.0 yrs) treated with DMARD-b (50.9% etanercept, 30.9% adalimumab,12.7% certolizumab, 5.5% golimumab): 19 with monotherapy and 36 associated with DMARD-c (72.2% methotrexate,13.9% leflunomide,13.9% others). 81.8% of patients were adherent to DMARD-b (89.5% with monotherapy). Adherence was higher for adalimumab (82.4%) than for other DMARD-b. In the combination therapy group, 58.3% were adherent to both (DMARD-b 77.7%, DMARD-c 72.2%). Adherence was higher to leflunomide (80.0%) than to methotrexate (69.2%). Among the 17 adherent patients receiving DMARD-b monotherapy, IA was in remission in 35.3%, low in 17.6%, moderate in 35.3% and high in 11.8%. Among non-adherent patients, 1 was in remission and 1 had low IA. Comparing the adherence and non-adherence groups receiving combination therapy, IA was in remission in 38.9% vs. 30.8% (p > 0.05), low in 22.2% vs. 30.8% (p > 0.05) and moderate in 38.9% vs. 38.4% (p > 0.05), respectively. Conclusion Adherence to DMARD-b was high in RA patients. Adherence to the combination therapy was lower, being higher for DMARD-b than for DMARD-c. Non-adherence to this combination therapy does not appear to increase IA. References and/or Acknowledgements Hughes. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDS. BMC Musculoskeletal Disorders 2013;14:286-94 No conflict of interest.

Background In April 2015, a national project was created to reduce the rate of patients with nosocomial infections by multiresistant bacterias (MRBs). This project had several recommendations, including ones for improving the use of antibiotics, especially against MRBs. Purpose To analyse the impact of the project on the consumption of antibiotics in our intensive care unit (ICU) during the first months after initiation of the project; and also to assess its economic impact and the number of patients colonised/infected by multiresistant Acinetobacter baumannii (MAB), the most important MRB in our ICU. Material and methods Retrospective, observational study to compare two periods of time (April–September 2015 vs April–September 2014). The number of defined daily dose per 100 admissions (DDD/100A) was used to evaluate consumption of the following antibiotics: glycopeptides, linezolid, daptomycin, tigecycline, colistin and carbapenems. The average cost of these drugs was used to do the economic assessment; we did not considerate either the indirect costs or the possible variation in the number of admissions between the two periods. We supposed that infected/colonised patients by MAB were those that had a positive microbiological test for Acinetobarter baummanni that was resistant to three or more families of antibiotics, including carbapenems. Results Overall antimicrobial consumption was reduced by 45.4% (56.3 vs 30.7 DDD/100A) and costs decreased by 32,9% (42783€ vs 28685€). All studied antibiotics reduced their consumption: 55% for carbapenems (20 vs 9 DDD/100A), 7.4% for linezolid (2.7 vs 2.5 DDD/100A), 56.5% for daptomycin (2.3 vs 1 DDD/100A), 50% for tigecycline (1.8 vs 0.9 DDD/100A) and 48.1 for colistin (16.2 vs 8.4 DDD/100A). There were the same numbers of patients (n = 13) with infection/colonisation with MAB in both studied periods. Conclusion Avoiding the use of unnecessary broad spectrum antibiotics and/or a shorter treatment period could reduce the selective pressure and number of MRBs. In addition, this also could lead to an important saving. Implementation of the project has reduced the use of all studied antibiotics for the treatment of MRBs, but no significant differences were found in the number of patients infected/colonised by MAB. This could be because more time is needed to detect this difference. No conflict of interest.

Diffuse osteosclerotic lesions are a very uncommon radiologic presentation in multiple myeloma. These lesions affect the axial skeleton and proximal limbs; they may be accompanied by osteolytic lesions in the course of the disease. In fact, in cases of diffuse osteosclerosis, the diagnosis of multiple myeloma is reached only after ruling out other, more common diseases. We present an exceptional case of multiple myeloma with diffuse osteosclerosis and highlight the differences between this entity and POEMS syndrome.

Background Metformin is widely used against diabetes type II mellitus. Its most severe adverse effect is lactic acidosis. Although rare, the risk of its development can be increased by kidney failure (KF). Purpose To report on pharmaceutical interventions (PIs) for preventing metformin-associated lactic acidosis (MALA) in diabetics admitted to hospital with KF and to evaluate their degree of acceptance. Material and methods This prospective study (October 2013–March 2014) included all metformin-treated patients admitted. Creatinine clearance (CrCl) was estimated with the Cockcroft-Gault equation. PIs were: PI-1, stop-order for metformin when CrCl Results During the study period, 234 metformin-treated patients were admitted (61.5% males), most frequently to the Cardiology Department (33.3%); mean (standard deviation) age was 71.3 (12.4) yrs; mean dose was 1,552.8 (560.7) mg/day. CrCl Conclusion A small proportion of these patients had KF. A large majority of these required PI, most frequently PI-1. The degree of satisfaction was high and was especially elevated for PI-1 when CrCl was References and/or acknowledgements AEMPS No conflict of interest.

Background In 2012, treatment protocols were agreed for the most common infections (pneumonia, urinary tract, bacteraemia and intra-abdominal catheter), approved by the relevant Committees and implemented in the Intensive Care Unit (ICU). Purpose This study aims to assess the impact on mortality, the financial situation and the profile of antimicrobial prescribing in the ICU before and after implementing the protocols. Material and methods Retrospective observational study comparing 2012 with 2013. The average cost of drugs was used for the financial assessment; we did not include associated indirect costs, nor the possible variation between the number of stays. The number of defined daily doses per 100 admissions (DDD/100 BD) was used to assess the prescription profile. DDD/Total 100 bed days were calculated, including all antimicrobials of the J01, J02 and J03 groups, and antimicrobials considered particularly relevant: carbapenems (imipenem and meropenem), linezolid, daptomycin, tigecycline and echinocandins (caspofungin and anidulafungin). Results The overall antimicrobial consumption was reduced by 17.3% (221.5 vs. 183.2 DDD/100 BD) and costs decreased by 23.9% (€257,476 vs. €195,891). The consumption of all antimicrobials studied reduced in 2013: 17.4% carbapenems (36.99 vs. 30.55 DDD/100 BD), linezolid 38.6% (3.76 vs. 2.31 DDD/100 BD), daptomycin 82.2% (2.86% vs. 0.51 DDD/100 BD), tigecycline 64.9% (4.98 vs. 1.75 DDD/100 BD) and echinocandins 13.8% (3.61 vs. 3 11 DDD/100 BD). ICU mortality was 12.8% in 2012 and 10.9% in 2013. Conclusion Antibiotic treatment protocols in the ICU have resulted in significant antibiotics savings, not only in financial terms but also in number of doses, without increasing mortality. This effect may be relevant to the need to optimise their use in order to prolong their useful life and reduce the selection of resistant organisms. In turn, protocols might be useful to reduce the variability of prescriptions. References and/or Acknowledgements No conflict of interest.

Background Drugs returned by patients have to be managed properly. Purpose To analyse drugs returned by patients and the associated financial impact after the implementation of a quality system (corrective action to ensure traceability of these drugs). Materials and methods Retrospective descriptive study of returns recorded after implementation of the improved procedure for ‘return of drugs for the patient’, from March 2011 to June 2013. The auxiliary records the return in formalised form indicating date, name of the patient, drug, number of units, batch and expiry date. The pharmacist validates the return based on a decision algorithm allowing the acceptance or rejection of the drug, taking into account whether it is in date, the physical appearance of the product and the storage conditions at home. If the drug is accepted, it is recorded back in the APD-Prism software and is labelled with ‘Return accepted drug’ so it can be traced to the patient to whom the returned medicine is dispensed. WE analysed the number of patients who returned drugs, units of returned drugs, therapeutic group of returned drugs (according to ATC classification), causes of the return and the financial impact associated with returned drugs. Results During the study period, 132 patients out of 1811 returned 77 different drugs corresponding to 400 lines of returns and 10,377 returned units. The main therapeutic groups and amounts of returned units were: J05 antivirals (44.7%), L01 antineoplastics (23%), J01 anti-infectives for systemic use (5.7%), C02 antihypertensives (4.4%), L04 immunosuppressants (4.3%), L03 immunomodulators (3.8%) and L02 endocrine drugs (3.3%). Returned drugs were accepted for the following reasons: end of treatment (31%), change of treatment (21.8%), death (12%), less than the expected treatment duration (11.8%), change of dose (11.3%), adverse reactions (10.3%), did not start the treatment (1.3%) and patient transfer (0.5%). The total value of returns was 188,862 € (0.77% of total), of which 4.6% were not accepted due to being expired (30%), defective (30%), badly stored (20%) and to opening of the primary multi-dose container (abiraterone) (20%). Conclusions A standard procedure for return of drugs facilitates the traceability of drugs and optimises the use of resources allocated to the budget line of drugs. It should inform patients of the importance of returning drugs no longer needed and their proper storage. The cost opportunity in the repackaging of drugs dispensed in the outpatient area should be discussed. No conflict of interest.

Background Satisfaction surveys are an important tool for ascertaining patient opinions. Purpose To evaluate the degree of satisfaction with interferon beta-1a pre-filled pens and patient preferences. Materials and methods We conducted a survey of patients who were treated with interferon beta-1a after the change from syringe to pre-filled pen. The survey, conducted by the pharmacist after the second device had been dispensed in the Outpatient department, picked up the following aspects: a) self-administration (yes or no), b) ease of use (preparation and injection), rated from 0 (more difficult) to 10 (easier), c) adverse effects (pain, hematoma, induration, redness and swelling and flu-like symptoms), d) preference for syringe or pre-filled pen and reason, e) overall satisfaction, rated from 0 (lowest) to 10 (highest). The assessment of pain at the injection site was measured by a visual analogue scale (VAS). Results All patients (44) completed the survey. 84% self-administered with the pen. The average score received both for ease of preparation and injection was 9. 9% did not like the pen because they had difficulty with device preparation and 2.3% because the safety lock release had failed. Adverse effects experienced: hematoma (13.6%), induration (13.6%), redness and swelling (6.8%) and flu-like symptoms (6.8%). Pain at the injection site obtained an average of 2.14. 88.7% preferred the pen, the main reason was ease of injection (56.4%) and other reasons were: the need to spend less time (25.7%), ease of preparation (7.7%), reduced pain (5.1%) and less anxiety due to the injection (5.1%). The overall patient satisfaction was 8.7. Conclusions The degree of satisfaction was high; some patients did prefer the syringe but weren’t given the option of continuing to use it. The majority preferred the pre-filled pen because of the ease of use. They agreed with the goal of changing the presentation in the Pharmacy Service. The change did not cause an increase in the perception of adverse reactions associated with the device. No conflict of interest.

Fixed drug eruption from paracetamol is not rare but no cases of nonpigmented fixed drug eruption caused by paracetamol have been previously described. We present the case of a woman who developed a nonpigmented fixed drug eruption following administration of paracetamol. Patch tests performed on affected and unaffected skin with paracetamol were negative. The diagnosis was made by a double-blind oral challenge with paracetamol. The patient tolerated aspirin.

A 34-year-old woman, after 2 weeks of treatment with phenytoin and amitriptyline, developed fever and cutaneous lesions consisting of a generalized maculopapular rash and eosinophilia. Her biochemical data showed abnormal liver functions with increased levels of SGOT, SGPT, LDH, gamma-glutamyl transpeptidase and alkaline phosphatase. The skin biopsy pattern was compatible with phenytoin drug eruption of the erythemamultiforme-like type (lymphocytic exocytosis, isolated dyskeratotic cells, vacuolation of basal cells and incontinence of pigment). The patch tests were positive with phenytoin (patch test biopsy showed a typical eczematous pattern). The patch test with amitriptyline was negative. An oral challenge with amitriptyline showed an erythematous maculopapular rash. The challenge with phenytoin was not carried out because the previously abnormal liver function tests contraindicated the challenge. Although there are a few cases reported, the patch tests could be useful for diagnosing phenytoin allergy. Cross-reactivity between phenytoin and amitriptyline is possible.

Background Hepatitis C virus (HCV) infection is a major health problem in the western world. Current treatment with interferon (IFN) and ribavirin (RBV) is able to produce a sustained virological response in approximately 50% of patients with genotype-1. Telaprevir (TPV) represents a change in the treatment of HCV. Purpose To describe the proportion of patients who had undetectable plasma HCV-RNA at week 4 and 12 of treatment, the haemoglobin and platelets level during treatment and the most frequently reported adverse events. Materials and Methods We conducted a retrospective study of all patients who started triple therapy in 2012. We collected demographics (age and sex), genotype, pre-treatment response, haemoglobin, platelets, plasma HCV-RNA at weeks 0, 4 and 12 and reported adverse events. Results Since January 2012, 9 patients began treatment with RBV+IFN+TPV with a mean of age of 49 (SD:6.2). 89% were male. Genotype-1a was predominant (95%). Five patients were previous non-responders, three were relapsers and one was missing. The mean haemoglobin at weeks 0, 4 and 12 was 15.5 (SD:1.2), 13.0 (SD:1.7), and 11.3.(SD:1.9) mg/dl respectively and the mean platelets at week 0, 4 and 12 were 217 (SD:142.4), 132 (SD:46.2) and 121 (SD:33.9) respectively. The mean of plasma HCV-RNA at the beginning was log 6.55 (SD:0.39). At week 4, 8 patients (88.9%) had undetectable plasma HCV-RNA and 1 had to discontinue treatment (HCV-RNA: log5.63). At week 12, 7 patients had undetectable plasma HCV-RNA. One patient had to discontinue treatment due to severe anaemia. The most frequent adverse event was anaemia (89%); in two cases it was even necessary to administer erythropoietin. Other adverse events were rash, fatigue and haemorrhoids. Conclusions Our rate of undetectable plasma HCV-RNA at week 4 is high (89%) which allowed TPV to be suspended at week 12 and RBV+IFN treatment to be shortened to 24 weeks. Anaemia was the major serious adverse event reported. No conflict of interest.

Background Appropriately timed cessation of chemotherapy is integral to the patient’s quality of life. Purpose To describe and evaluate the use of chemotherapy in cancer patients in their last days of life. Materials and Methods Retrospective observational study that included all cancer patients who died in our hospital in 2011. Information sources used were: a) Mambrino for the age, date of death of the patient and clinical charts; b) Oncofar to record the type of cancer, the last cycle of intravenous (IV) chemotherapy received, the historic administration, lines of treatment and the percentage of the last dose received; c) APD-Athos to review data from the patient’s hospital stay and outpatient oral cytostatics dispensing. We collected for each patient their demographics, pharmacotherapy, the temporal interval between the last chemotherapy administration and death of the patient and the number of days in hospital one month before death. Results A total of 94 patients (30% female) died in 2011 in our hospital. Of these, 10 patients didn’t receive chemotherapy, 10 received IV chemotherapy combined with oral, 4 received oral chemotherapy alone and 70 IV chemotherapy alone. Tumours with the highest number of deaths were non-small cell lung cancer (21), head and neck cancer (11) and colorectal cancer (10). The most common last chemotherapy regimens were combinations of carboplatin (16) (especially with pemetrexed and paclitaxel), gemcitabine (11) (mostly alone), combinations of cisplatin (9), paclitaxel (9) (alone or combined with carboplatin) and monoclonal antibodies (9) (in 67% combined with bevacizumab); the most frequent oral chemotherapy drugs were erlotinib (4) and temozolomide (3). Of the 80 patients who received IV chemotherapy, 27.5% (22) received chemotherapy in the last 14 days of life, another 27.5% (22) received chemotherapy between 15 and 30 days before death, 21.25% (17) between 31 and 60 days, 13.75% (11) between 61 and 90 days and 10% (8) more than 90 days before death. In addition, 14% (12) started a new IV chemotherapy regimen a month before death. About lines of treatment, 45.25% (38) of the patients received first-line chemotherapy, 20.25% (17) in second line, 21.4% (18) in third line and 13.1% (11) received more than 3 lines of chemotherapy. In 48.75% (39), the percentage of the last dose of IV chemotherapy administered was ≤ 80%. All patients were admitted to the Oncology floor at some point in the last 30 days of life, with an average stay of 9.73 days. Conclusions The percentage of patients receiving IV chemotherapy in the last 14 days of life and that of those who started with a new regimen a month before death are much higher in our hospital than in similar studies. In view of the results obtained, more than half of these patients received IV chemotherapy in the last month of life. This makes us ask ourselves what factors contributed to this decision to treat, were the benefit and toxicity correctly assessed and was it is really necessary to have active cancer treatment in the last days of life? No conflict of interest.