Nanographene-Based Decoration as a Panchromatic Antenna for Metalloporphyrin Conjugates.

Porphyrins, a type of heterocyclic aromatic compounds consisting of tetrapyrroles connected by four substituted methine groups, are appealing building blocks for solar energy applications. However, their photosensitization capability is limited by their large optical energy gap, which results in a mismatch in absorption toward efficient harvesting of the solar spectrum. Porphyrin π-extension by edge-fusing with nanographenes can be employed for narrowing their optical energy gap from 2.35 to 1.08 eV, enabling the development of porphyrin-based panchromatic dyes with an optimized energy onset for solar energy conversion in dye-sensitized solar fuel and solar cell configurations. By combining time-dependent density functional theory with fs transient absorption spectroscopy, it is found that the primary singlets, which are delocalized across the entire aromatic part, are transferred into metal centred triplets in only 1.2 ps; and subsequently, relax toward ligand-delocalized triplets. This observation implies that the decoration of the porphyrin moiety with nanographenes, while having a large impact on the absorption onset of the novel dye, promotes the formation of a ligand-centred lowest triplet state of large spatial extension, potentially interesting for boosting interactions with electron scavengers. These results reveal a design strategy for broadening the applicability of porphyrin-based dyes in optoelectronics.

Precise tuning of interlayer electronic coupling in layered conductive metal-organic frameworks.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have attracted increasing interests for (opto)-electronics and spintronics. They generally consist of van der Waals stacked layers and exhibit layer-depended electronic properties. While considerable efforts have been made to regulate the charge transport within a layer, precise control of electronic coupling between layers has not yet been achieved. Herein, we report a strategy to precisely tune interlayer charge transport in 2D c-MOFs via side-chain induced control of the layer spacing. We design hexaiminotriindole ligands allowing programmed functionalization with tailored alkyl chains (HATI_CX, X = 1,3,4; X refers to the carbon numbers of the alkyl chains) for the synthesis of semiconducting Ni3(HATI_CX)2. The layer spacing of these MOFs can be precisely varied from 3.40 to 3.70 Å, leading to widened band gap, suppressed carrier mobilities, and significant improvement of the Seebeck coefficient. With this demonstration, we further achieve a record-high thermoelectric power factor of 68 ± 3 nW m-1 K-2 in Ni3(HATI_C3)2, superior to the reported holes-dominated MOFs.

An overview of the use and misuse/abuse of opioid analgesics in different world regions and future perspectives.

Opioids are an important therapeutic option for severe resistant chronic pain but, in the absence of proper oversight, their use has risks. The level of prescription opioid misuse/abuse differs among countries, due to differences in healthcare systems and pain management approaches. However, evaluating the true dimension of prescription opioid misuse/abuse is complicated by statistical reporting which often does not differentiate between prescription and illicit opioid use, or between prescription opioid use by patients and nonpatients, highlighting a need for greater uniformity. Parallel efforts to educate patients and the general public about opioid risks, facilitate appropriate analgesic prescribing and identify alternative formulations or options to use instead of or with opioids, may contribute to optimizing prescription opioid use for pain management.

Cove-Edged Hexa-peri-hexabenzo-bis-peri-octacene: Molecular Conformations and Amplified Spontaneous Emission.

The bottom-up synthesis of an unprecedentedly large cove-edged nanographene, hexa-peri-hexabenzo-bis-peri-octacene (HBPO), is reported in this work. Chiral high-performance liquid chromatography and density functional theory (DFT) calculations revealed multiple conformations in solution. Two different molecular conformations, "waggling" and "butterfly", were found in crystals by X-ray crystallography, and the selectivity of conformations could be tuned by solvents. The optoelectronic properties of HBPO were investigated by UV/Vis absorption and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations. The contorted geometry and branched alkyl groups suppress the aggregation of HBPO in solution, leading to a high fluorescence quantum yield of 79 %. The optical-gain properties were explored through transient absorption and amplified spontaneous emission spectroscopies, which enrich the choices of edge structures for potential applications in laser cavities.

Covalent modification of franckeite with maleimides: connecting molecules and van der Waals heterostructures.

The building of van der Waals heterostructures and the decoration of 2D materials with organic molecules share a common goal: to obtain ultrathin materials with tailored properties. Performing controlled chemistry on van der Waals heterostructures would add an extra level of complexity, providing a pathway towards 2D-2D-0D mixed-dimensional heterostructures. Here we show that thiol-ene-like "click" chemistry can be used to decorate franckeite, a naturally occurring van der Waals heterostructure with maleimide reagents. ATR-IR and NMR analyses corroborate the Michael addition mechanism via the formation of a S-C covalent bond, while Raman and HR-TEM show that the SnS2-PbS alternating structure of franckeite is preserved, and suggest that SnS2 reacts preferentially, which is confirmed through XPS. We illustrate how this methodology can be used to add functional molecular moieties by decorating franckeite with porphyrins. UV-vis-NIR spectroscopy confirms that the chromophore ground state remains operative, showing negligible ground-state interactions with the franckeite. Excited-state interactions across the hybrid interface are revealed. Time-resolved photoluminescence confirms the presence of excited-state deactivation in the linked porphyrin ascribed to energy transfer to the franckeite.

Key factors influencing clinical and functional outcomes in extracapsular proximal femur fractures: the role of early weight-bearing - one-year follow-up cohort of 495 patients.

Aim To establish a correlation between immediate post-surgical weight bearing in extracapsular hip fractures and final functional outcome as well as to study the correlation between immediate post-surgical weight bearing and morbidity and mortality during the first year. Methods Retrospective observational cohort study including 495 consecutive patients ≥75 years old operated of extracapsular proximal femur fracture. Medical records were reviewed and information of demographic data, radiological evolution, time to weight-bearing, mortality rate, medical and surgical complications and final ambulation status were recorded. Results Patients' mean age was 87 years; 378 (76.4%) were females. One-year mortality rate was 21.2%. Immediate weight bearing was associated with: decreased hospital stays (7.5 days vs. 9.2 days; p=0.001) and decreased medical complications (78.3% vs. 82.3 %; p=0.02). Surgical complications prevalence was comparable (4.4% vs. 7.8 %; p=0.43) within the groups. Despite mortality rate was lower in patients with immediate weight bearing (21%) compared with delayed weight bearing (21.4%), the difference was not statistically significant (p=0.9). Conclusion Immediate weight bearing was associated with shorter hospital stay and fewer medical complications, improving functional outcome. Also, no correlation was found between immediate weight bearing and increased surgical complications or mortality rate during first year after surgery.

Localised neuropathic pain in the primary care setting: a cross-sectional study of prevalence, clinical characteristics, treatment patterns, quality of life and sleep performance.

BACKGROUND: Localised Neuropathic Pain (LNP) is challenging to diagnose and manage in primary care. OBJECTIVE: To describe clinical characteristics, treatment patterns, quality of life and sleep performance of patients with LNP and estimate its prevalence in primary care. METHODS: Cross-sectional study in 4 European countries. Patients were identified using a screening tool for LNP. Patients completed the EQ-5D VAS score and Chronic Pain Sleep Inventory (CPSI). RESULTS: There were 1030 LNP patients for analysis. They presented a median pain intensity of 6.0 (IQR 4.0-7.0) with a median duration of 30.9 months (IQR 12.0-75.3), despite 97% receiving pain treatment. Main sites affected were the limbs (62% upper/58% lower) and spine (41%). Main aetiologies were neuropathic low back pain (47%), post-surgical neuropathic pain (17%), and diabetic poly-neuropathy (12%). Thirty percent received a single analgesic (2% topical), while combinations comprised 43% systemic-systemic, 24% topical-systemic, 1% topical-topical. Medications included NSAIDs (45%), anticonvulsants (38%), WHO step 2 opioids (35%), and topical analgesics (27%). In the previous 6 months, 40% had switched treatment. The mean (SD) EQ-5D VAS score was 58 (22.3) and the mean (SD) EQ-5D summary score (UK tariff) was 0.62 (0.25). Patients had a CPSI mean index of 41/100, and sleeping pills were used by 33% of patients. The standardized prevalence of LNP by age and sex was 2.01% in the general population and 43.3% among chronic pain patients. CONCLUSIONS: Many LNP patients reported pain intensities of six on a ten-point scale in average for durations longer than 2.5 years, with quality of life and sleep performance affected, with frequent treatment combinations and switches, suggesting suboptimal pain management.

Epidemiología, repercusión clínica y objetivos terapéuticos en la artrosis / Epidemiology, clinical impact and therapeutic objectives in osteoarthritis

La artrosis es uno de los principales problemas de salud en todos los países, más prevalente en los países desarrollados probablemente debido a factores como el aumento de la longevidad, el sedentarismo y la obesidad. Las estadísticas de salud muestran un continuo crecimiento de su incidencia e importancia global sobre la discapacidad. El objetivo es analizar y sintetizar el problema de salud que representa la artrosis, aportando datos epidemiológicos de prevalencia, repercusión clínica, pérdida de calidad de vida y costes que ocasiona. Se muestran los objetivos terapéuticos que son clínicamente relevantes, tanto aquellos preventivos o modificables como los cofactores que modifican el grado de respuesta a los mismos. Se trata de una revisión sistemática de la literatura de los últimos 10 años en la base de datos PubMed para términos “Mesh” relacionados con epidemiología, prevención, tratamiento y resultados informados por el paciente para artrosis de rodilla y cadera. Hemos encontrado una gran variabilidad en los resultados epidemiológicos comunicados, consecuencia de los diferentes criterios de inclusión y metodología de los estudios, mostrando prevalencias del 83 % en estudios con resonancia magnética en pacientes asintomáticos hasta el 3,8 % de artrosis sintomática de rodilla en estudios poblacionales en adultos. La edad, el sexo femenino, la etnia y la obesidad parecen ser los factores más importantes relacionados con la enfermedad. Otros factores como los genéticos, biomecánicos (consecuencia de lesiones deportivas y ocupacionales), hormonales, el síndrome metabólico y el sedentarismo han mostrado una clara asociación con la enfermedad. El coste directo e indirecto de la artrosis representa entre el 0,5 y el 1 % del PIB, según países. La revisión de los objetivos terapéuticos muestra que los pacientes perciben como cambios mínimamente relevantes aquellas terapias...(AU)

Osteoarthritis is one of the main health problems in all countries, most prevalent in developed countries, probably due to factors such as increased longevity, a sedentary lifestyle and obesity. Health statistics show a continued growth in its overall impact and importance on disability. The objective is to analyze and synthesize the health problem posed by osteoarthritis, providing epidemiological data on prevalence, clinical impact, loss of quality of life and costs it causes. Those therapeutic objectives that are clinically relevant, will be shown, both those preventive and modifiable as well as the cofactors that modify the degree of response to them. Systematic review of the literature of the last 10 years in the Pubmed database for terms "Mesh" related to epidemiology, prevention, treatment, and patient reported outcomes for knee and hip osteoarthritis.We have found great variability in reported epidemiological results, a consequence of the different inclusion criteria and methodology of studies, showing prevalence of 83% in Magnetic Resonance studies with asymptomatic patients up to 3.8% of symptomatic knee osteoarthritis in adult population studies. Age, female sex, ethnicity and obesity seem like the most important factors related to the disease. Other factors such as genetics, biomechanics resulting from sports and occupational injuries, hormonal, metabolic syndrome and sedentary lifestyles have shown a clear association with the disease. The direct and indirect cost of osteoarthritis represents between 0.5 and 1% of GDP, according to countries. The review of therapeutic goals shows that patients perceive as minimally relevant changes those therapies that achieve a decrease of 2 points or 33 % on the VAS Analypain scale, but these cut-off points will depend on the affected joint and the severity of the initial pain...(AU)

Sociedad Española del Dolor (SED). Recomendaciones asistenciales para unidades de dolor ante la normalización progresiva de la actividad durante la pandemia por COVID-19 / Spanish Pain Society (SPS). Healthcare recommendations for pain units in the face of progressive normalization of activity during the COVID-19 pandemic

INTRODUCCIÓN: La infección por SARS-CoV-2 es una nueva infección viral que ha emergido en forma de pandemia, con un espectro clínico respiratorio y multisistémico, que ocasiona una elevada morbimortalidad. Su rápida expansión es dependiente de la ausencia de exposición e inmunidad previas, la ausencia de vacuna y de tratamientos específicos, y de un mecanismo de transmisión por vía respiratoria y contacto con mucosas y proximidad entre los individuos, incluso asintomáticos. La necesidad de protección sobre la población y sus profesionales sanitarios obliga a establecer protocolos de control y prevención de exposiciones. Una de las nuevas situaciones generadas es el restablecimiento de la actividad asistencial en condiciones de seguridad, que en muchos casos son específicas de cada especialidad. OBJETIVO: Elaborar un documento de recomendaciones clínicas y de gestión que oriente a los gestores y personal asistencial de las unidades de dolor sobre cómo afrontar el retorno escalonado a la labor asistencial con la mejor evidencia disponible. El documento tiene en cuenta la seguridad de los pacientes y profesionales en el contexto de la pandemia por SARS-CoV-2, aunque reconocemos que el entorno cambiante puede modificar en un futuro cercano las recomendaciones. METODOLOGÍA: Tras una revisión narrativa de la literatura en PubMed, Google Scholar, y recomendaciones de autoridades competentes y sociedades científicas, la Sociedad Española del Dolor publicó un primer documento (V1.0) el 21 de abril del 2020 en su web (www.sedolor.es) que fue compartido con los socios y presidentes de las sociedades autonómicas de dolor, dejando abierta la posibilidad para su mejora a través de un correo (posicionamiento.covid.sed@sedolor.es), donde se han recibido sugerencias hasta la Versión 2.1, publicada el 13 de mayo de 2020. Algunos socios también se han dirigido directamente a la junta directiva y sus aportaciones han sido asimismo evaluadas e incorporadas cuando ha sido posible. El presente documento está basado en esta última versión. RESULTADOS: El documento ofrece una serie de recomendaciones generales y otras adaptadas a los diferentes entornos asistenciales, desde la asistencia telemática a la organización de los espacios físicos de consulta, como la atención hospitalaria, las salas de técnicas o el quirófano. Las recomendaciones contemplan desde las medidas higiénicas y protección al diagnóstico de la enfermedad, la categorización del riesgo, las modificaciones en las opciones farmacológicas y técnicas analgésicas disponibles, así como un documento de acompañamiento al consentimiento informado. CONCLUSIONES: Una nueva realidad asistencial se está imponiendo. Esta realidad no solo pasa por unos estándares de seguridad adaptados a la contagiosidad y otros efectos del virus, si no también a un nuevo modelo asistencial que incorpore las herramientas telemáticas con seguridad tecnológica y un adecuado marco legal. Las secuelas biológicas y psicológicas deletéreas del virus sobre los pacientes con dolor aún no han sido esclarecidas plenamente por lo que debemos estar atentos, previniendo y tratando dicha posibilidad

INTRODUCTION: SARS-CoV-2 infection is a new viral infection that has emerged in the form of a pandemic, with a respiratory and multisystemic clinical spectrum, which causes high morbidity and mortality. Its rapid expansion is dependent on the absence of previous exposure and immunity, the absence of a vaccine and specific treatments, as well as its mechanism of air transmission and contact with mucous membranes, including asymptomatic individuals. The need for protection on the population and its health professionals requires the establishment of exposure and prevention protocols. One of the new situations generated is the need for a safe return to normal healthcare activities, which in many cases are specific to each specialty. OBJECTIVE: To elaborate a document of clinical and management recommendations to guide managers and staff of pain units on how to face the staggered return to normal care with the best available evidence. The document takes into account the safety of patients and professionals in the context of the SARS-CoV-2 pandemic, although we recognize that the changing environment may change the recommendations in the near future. METHODOLOGY: After a narrative review of the literature on PubMed , Google Scholar, and recommendations of competent authorities and scientific societies, The Spanish Pain Society published a first document (V1.0) on April 21st 2020 into its WEB (www.sedolor.es), which was shared with the members of the society as well as the presidents of the Spanish autonomous pain societies, leaving open the possibility for improvement through an email posicionamiento.covid.sed@sedolor.es, where suggestions have been received up to Version 2.1 published on May 13th, 2020. Some partners have also addressed the board of directors directly and their contributions have also been evaluated and incorporated when possible. This document is based on this latest version. RESULTS: The document offers a series of general recommendations and others adapted to the different healthcare settings, from telematic assistance to the organization of physical consultation spaces, hospital care, interventional rooms and operating theaters. The recommendations cover from the hygienic measures and protection, to the diagnosis of the disease, risk categorization, the potential modifications in the pharmacological options and available analgesic techniques, as well as an accompanying document to the informed consent. CONCLUSIONS: A new healthcare reality is prevailing. This reality not only goes through security standards adapted to the contagiousness and other consequences of the virus, but also a new healthcare model that incorporates telematic tools with technological security and an adequate legal framework. The deleterious biological and psychological consequences of the virus on pain patients have not yet been fully clarified, so we must be vigilant, preventing and treating this possibility

Top 10 cuestiones bioéticas en dolor / Top 10 bioethical issues in pain

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Monolayer black phosphorus by sequential wet-chemical surface oxidation.

We report a straightforward chemical methodology for controlling the thickness of black phosphorus flakes down to the monolayer limit by layer-by-layer oxidation and thinning, using water as solubilizing agent. Moreover, the oxidation process can be stopped at will by two different passivation procedures, namely the non-covalent functionalization with perylene diimide chromophores, which prevents the photooxidation, or by using a protective ionic liquid layer. The obtained flakes preserve their electronic properties as demonstrated by fabricating a BP field-effect transistor (FET). This work paves the way for the preparation of BP devices with controlled thickness.

Solvent exfoliation stabilizes TiS2 nanosheets against oxidation, facilitating lithium storage applications.

Titanium disulfide is a promising material for a range of applications, including lithium-ion battery (LIB) anodes. However, its application potential has been severely hindered by the tendency of exfoliated TiS2 to rapidly oxidize under ambient conditions. Herein, we confirm that, although layered TiS2 powder can be exfoliated by sonication in aqueous surfactant solutions, the resultant nanosheets oxidise almost completely within hours. However, we find that upon performing the exfoliation in the solvent cyclohexyl-pyrrolidone (CHP), the oxidation is almost completely suppressed. TiS2 nanosheets dispersed in CHP and stored at 4 °C in an open atmosphere for 90 days remained up to 95% intact. In addition, CHP-exfoliated nanosheets did not show any evidence of oxidation for at least 30 days after being transformed into dry films even when stored under ambient conditions. This stability, probably a result of a residual CHP coating, allows TiS2 nanosheets to be deployed in applications. To demonstrate this, we prepared lithium ion battery anodes from nano : nano composites of TiS2 nanosheets mixed with carbon nanotubes. These anodes displayed reversible capacities (920 mA h g-1) close to the theoretical value and showed good rate performance and cycling capability.

Percolation Effects in Electrolytically Gated WS2/Graphene Nano:Nano Composites.

Mixed networks of conducting and nonconducting nanoparticles show promise in a range of applications where fast charge transport is important. While the dependence of network conductivity on the loading level of conductive additive is well understood, little is known about the loading dependence of mobility and carrier density. This is particularly important as the addition of graphene might lead to increases in the mobility of semiconducting nanosheet network transistors. Here, we use electrolytic gating to investigate the transport properties of spray-coated composite networks of graphene and WS2 nanosheets. As the graphene loading is increased, we find that both conductivity and carrier density increase in line with the percolation theory with percolation thresholds (∼8 vol %) and exponents (∼2.5) consistent with previous reporting. Perhaps surprisingly, we find the mobility increases modestly from ∼0.1 cm2/V s (for a WS2 network) to ∼0.3 cm2/V s (for a graphene network) which we attribute to the similarity between WS2-WS2 and graphene-graphene junction resistances. In addition, we find both the transistor on- and off-currents to scale with loading according to the percolation theory, changing sharply at the percolation threshold. Through fitting, we show that only the current in the WS2 network changes significantly upon gating. As a result, the on-off ratio falls sharply at the percolation threshold from ∼104 to ∼2 at higher loading. Reflecting on these results, we conclude that the addition of graphene to a semiconducting network is not a viable strategy to improve transistor performance as it reduces the on:off ratio far more than it improves the mobility.

Five year long term results of total joint arthroplasties in the treatment of trapeziometacarpal osteoarthritis.

INTRODUCTION: Trapeziometacarpal (TMC) osteoarthritis is a common disease. Patients with advanced disease who have failed conservative treatment have different surgical options, including total joint prosthesis. The aim of this study was to investigate the long-term outcome and complications of trapeziometacarpal (TMC) total arthroplasty. MATERIALS AND METHODS: One hundred and forty-seven patients with TMC osteoarthritis were surgically treated with TMC arthroplasty, and one hundred and thirty-seven patients were seen for follow-up (102 women and 35 men). At follow -up patients were asked to complete a visual linearanalogue scale (VAS) for satisfaction with the result of the operation and persisting pain from the thumb, the Spanish validated Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was used to evaluate function of the affected hand.(9) The radiological examination consisted of posterior-anterior and oblique radiographs. In preoperative radiographs Eaton-Little was used, and in postoperative radiographs were assessed with regard to implant loosening and alignment. RESULTS: The subjective outcome was satisfactory in 126 cases (92 %), 14 (12 %) patients would undergo the same procedure in the other hand. The DASH questionnaireswere 19.55 (range 5.6-33,5) on average, and EVA was 1 on average. The mean key pinch strength was 5.8 Kg at 5 years follow-up. The most frequent postoperative complication was De Quervain tenosynovitis (21%), other complications were: Cup loosening (3.6%), traumatic dislocation (3,6%). The prosthesis was removed in nine cases (7%). There were four intraoperative complications. The survival rate for ARPE prosthesis was 92,7% at 60,5 months. TMC total arthroplasty offers a reliable treatment alternative in patients with thumb carpometacarpal joint osteoarthrosis which conservatives' treatment had failed. CONCLUSIONS: The TMC joint prosthesis is an option for patients with TCM osteoarthritis, provides satisfactory outcomes and has a low failure rate.(www.actabiomedica.it).

Liquid phase exfoliation of MoO2 nanosheets for lithium ion battery applications.

Molybdenum dioxide (MoO2) is a layered material which shows promise for a number of applications in the electrochemical energy storage arena. Mostly studied as a bulk layered material, MoO2 has not previously been exfoliated in large quantities. Here we demonstrate the liquid phase exfoliation of MoO2 in the solvent isopropanol, yielding reasonable amounts of good quality nanosheets. However, we found that, when dispersed in isopropanol under ambient conditions, MoO2 nanosheets are gradually oxidized to higher oxides such as MoO3 over a period of days. Conversely, if the nanosheets are processed into dried films immediately after exfoliation, and before oxidation has had a chance to progress, the nanosheets are relatively stable under ambient conditions, remaining unoxidised unless the films are heated. We also found that MoO2 nanosheets can be size selected by controlled centrifugation and show size-dependent optical properties. This allows us to propose spectroscopic metrics which allow concentration- and size-estimation from extinction spectra. Finally, we found that liquid-exfoliated MoO2 nanosheets could be used to produce lithium ion battery anodes with capacities of up to 1140 mA h g-1.

Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria.

OBJECTIVE: Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness. METHODS: A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). RESULTS: Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete. CONCLUSIONS: A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.

Electroconductive Biohybrid Collagen/Pristine Graphene Composite Biomaterials with Enhanced Biological Activity.

Electroconductive substrates are emerging as promising functional materials for biomedical applications. Here, the development of biohybrids of collagen and pristine graphene that effectively harness both the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching native cardiac tissue) obtainable with pristine graphene is reported. As well as improving substrate physical properties, the addition of pristine graphene also enhances human cardiac fibroblast growth while simultaneously inhibiting bacterial attachment (Staphylococcus aureus). When embryonic-stem-cell-derived cardiomyocytes (ESC-CMs) are cultured on the substrates, biohybrids containing 32 wt% graphene significantly increase metabolic activity and cross-striated sarcomeric structures, indicative of the improved substrate suitability. By then applying electrical stimulation to these conductive biohybrid substrates, an enhancement of the alignment and maturation of the ESC-CMs is achieved. While this in vitro work has clearly shown the potential of these materials to be translated for cardiac applications, it is proposed that these graphene-based biohybrid platforms have potential for a myriad of other applications-particularly in electrically sensitive tissues, such as neural and neural and musculoskeletal tissues.

The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized Neuropathic Pain, and Clinical Evidence Supporting its Use.

When peripheral neuropathic pain affects a specific, clearly demarcated area of the body, it may be described as localized neuropathic pain (LNP). Examples include postherpetic neuralgia and painful diabetic neuropathy, as well as post-surgical and post-traumatic pain. These conditions may respond to topical treatment, i.e., pharmaceutical agents acting locally on the peripheral nervous system, and the topical route offers advantages over systemic administration. Notably, only a small fraction of the dose reaches the systemic circulation, thereby reducing the risk of systemic adverse effects, drug-drug interactions and overdose. From the patient's perspective, the analgesic agent is easily applied to the most painful area(s). The 5% lidocaine-medicated plaster has been used for several years to treat LNP and is registered in approximately 50 countries. Many clinical guidelines recommend this treatment modality as a first-line option for treating LNP, particularly in frail and/or elderly patients and those receiving multiple medications, because the benefit-to-risk ratios are far better than those of systemic analgesics. However, some guidelines make only a weak recommendation for its use. This paper considers the positioning of the 5% lidocaine-medicated plaster in international treatment guidelines and how they may be influenced by the specific criteria used in developing them, such as the methodology employed by randomized, placebo-controlled trials. It then examines the body of evidence supporting use of the plaster in some prevalent LNP conditions. Common themes that emerge from clinical studies are: (1) the excellent tolerability and safety of the plaster, which can increase patients' adherence to treatment, (2) continued efficacy over long-term treatment, and (3) significant reduction in the size of the painful area. On this basis, it is felt that the 5% lidocaine-medicated plaster should be more strongly recommended for treating LNP, either as one component of a multimodal approach or as monotherapy.

The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence.

Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug-drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events.