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Curr Protoc Stem Cell Biol ; 50(1): e93, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31479593


This article describes a screening platform to identify compounds that affect human embryonic vascular development. The procedure comprises the generation of human embryonic-like endothelial cells (ECs) from human pluripotent stem cells (hPSCs) and subsequent maturation under arterial flow conditions; the use of these cells for the high-throughput screening of small molecules that specifically inhibit the survival of embryonic-like ECs; the confirmation of the hits in embryonic-like ECs cultured under flow shear stress; and final validation in mouse embryonic ECs. The embryonic-like ECs express embryonic genes including DLL1, EPHB2, LYN, TEK, ID1, NRP2, CAST, FLT1, IGF1, DKK3, NIN, LEF1, and SORBS3. The entire screening procedure (without the validation step) can be completed within 1 month. This platform is an alternative/complement to standard animal protocols for assessing the effects of chemicals on embryonic vascular development. © 2019 by John Wiley & Sons, Inc.

Rev Bras Enferm ; 72(4): 1119-1123, 2019 Aug 19.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31432974


OBJECTIVE: to present an academic practice experienced by professors in a curricular unit of the public health field entitled "Comprehensive health care", offered in the undergraduate nursing course of a public university. METHODS: experience report of dialogic activities between professors and undergraduates. RESULTS: it was possible to discuss nursing care from the perspective of comprehensiveness, which allowed the understanding of the need to broaden the scope regarding the practices conducted in primary care and enabled the attribution of new meanings to the actions experienced by undergraduate students in their curricular internships; thus, contributing to the training of a professional with critical and creative capacity. FINAL CONSIDERATIONS: the students were able to understand that quality care should go beyond complaint-behavior, providing care based on a networked health service structure aligned with SUS policies and programs.

Nanoscale ; 11(30): 14312-14321, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322143


Bioinstructive scaffolds for regenerative medicine are characterized by intrinsic properties capable of directing cell response and promoting wound healing. The design of such scaffolds requires the incorporation of well-defined physical properties that mimic the native extracellular matrix (ECM). Here, inspired by epithelial tissue morphogenesis, we present a novel approach to code nanofiber materials with controlled hierarchical wavy structures resembling the configurations of native EMC fibers through using thermally shrinking materials as substrates onto which the fibers are deposited. This approach could serve as a platform for fabricating functional scaffolds mimicking various tissues such as trachea, iris, artery wall and ciliary body. Modeling affirms that the mechanical properties of the fabricated wavy fibers could be regulated through varying their wavy patterns. The nanofibrous scaffolds coded with wavy patterns show an enhanced cellular infiltration. In addition, we further investigated whether the wavy patterns could regulate transforming growth factor-beta (TGF-ß) production, a key signalling pathway involved in connective tissue development. Our results demonstrated that nanofibrous scaffolds coded with wavy patterns could induce TGF-ß expression without the addition of a soluble growth factor. Our new approach could open up new avenues for fabricating bioinstructive scaffolds for regenerative medicine.

Acta Paul. Enferm. (Online) ; 32(3): 334-340, Mai.-Jun. 2019. tab, graf
Artigo em Português | LILACS-Express | ID: biblio-1010807


Resumo Objetivo Identificar as principais literaturas científicas sobre o cuidado prestado ao agressor familiar frequente e apresentar as experiências exitosas mais relevantes. Métodos Revisão integrativa da literatura, com busca de artigos publicados entre os anos de 2008 a 2017, nas bases de dados MEDLINE, CINAHL e SciELO. Resultados Dos 1.496 artigos identificados, 15 atenderam aos critérios de inclusão. A análise desses estudos revelou duas categorias: Fatores intervenientes à agressividade intrafamiliar e Medidas exitosas para cuidado ou reabilitação de agressores familiares. Conclusão Há escassez de produção sobre a temática em países emergentes. Aspectos como padrões intergeracionais e vivência de situações violentas na infância podem ser intervenientes para o comportamento agressivo contra a família. São apontadas como medidas exitosas para o cuidado do agressor familiar a meditação de atenção plena, o aconselhamento pessoal, a melhoria do padrão do sono, participação em programas de prevenção e em formas de psicoterapia.

Resumen Objetivo Identificar las principales literaturas científicas sobre el cuidado ofrecido al agresor familiar recurrente y presentar las experiencias exitosas más relevantes. Métodos Revisión integradora de literatura, con búsqueda de artículos publicados entre 2008 y 2017 en las bases de datos MEDLINE, CINAHL y SciELO. Resultados De los 1496 artículos identificados, 15 cumplieron los criterios de inclusión. El análisis de estos estudios reveló dos categorías: factores intervinientes en la agresividad intrafamiliar y medidas exitosas para cuidado o rehabilitación de agresores familiares. Conclusión Hay escasez de producción sobre este tema en países emergentes. Aspectos como patrones intergeneracionales y vivencia de situaciones violentas durante la infancia pueden ser intervinientes en el comportamiento agresivo contra la familia. Se señalaron las siguientes medidas exitosas para el cuidado del agresor familiar: meditación de atención plena, consejos personales, mejora del patrón del sueño, participación en programas de prevención y tipos de psicoterapia.

Abstract Objectives Identifying the main articles in scientific literature on care of perpetrators of repeat family violence and presenting the most relevant successful experiences. Methods Integrative literature review consisting of a survey for articles published from 2008 to 2017 indexed in MEDLINE, CINAHL, and SciELO. Results Out of the 1,496 identified articles, 15 met all inclusion criteria. After analysis of all studies included, two categories were elaborated: intervening factors for intra-familial violence and successful measures for the treatment or rehabilitation of perpetrators of family violence. Conclusion Literature on the topic is scarce in emerging countries. Aspects such as intergenerational patterns and experience of violence in childhood may be intervening factors for aggressive family behavior. Mindfulness meditation, individual counseling, improvement in sleep pattern, participation in prevention programs, and forms of psychotherapy were shown to be successful measures for the care of perpetrators.

Stem Cell Res Ther ; 10(1): 135, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109365


BACKGROUND: Xenotransplantation of spermatogonial stem cells (SSCs) has become a popular topic in various research fields because manipulating these cells can provide insights into the mechanisms associated with germ cell lines and the entire spermatogenesis process; moreover, these cells can be used in several biotechnology applications. To achieve successful xenotransplantation, the in vitro microenvironment in which SSCs are cultured should be an ideal microenvironment for self-renewal and similar to the in vivo testicular microenvironment. The age of the donor, the correct spermatogenesis cycle, and the quality of the donor tissue are also important. Although cell culture-related factors, such as the in vitro supplementation of hormonal factors, are known to promote successful xenotransplantation in mice, little is known about the influence of these factors on SSCs in vitro or in vivo in other mammalian species, such as dogs (Canis lupus familiaris). In this context, the goals of this study were to test the effect of follicle-stimulating hormone (FSH) on canine spermatogonial stem cell (cSSC) cultures since this hormone is related to the glial cell-derived neurotrophic factor (GDNF) signaling pathway, which is responsible for the self-renewal and maintenance of these cells in vivo, and to investigate the microenvironment of the SSC culture after FSH supplementation. Additionally, in vivo analyses of transplanted FSH-supplemented cSSCs in the testes of infertile mice were performed to assess the capacity of cSSCs to develop, maintain, and restore spermatogenesis. METHODS: SSCs from canine prepubertal testes (aged 3 months) were cultured in vitro in the presence of FSH (10 IU L-1). GFRA1 transcript expression was detected to confirm the spermatogonia population in culture and the effect of FSH on these cells. The protein and transcript levels of late germ cell markers (GFRA1, DAZL, STRA8, PLZF, and CD49f) and a pluripotency marker (OCT4) were detected at 72 and 120 h to confirm the cSSC phenotype. In vivo experiments were performed by transplanting GFP+ cSSCs into infertile mice, and a 10-week follow-up was performed. Histological and immunofluorescence analyses were performed to confirm the repopulation capacity after cSSC xenotransplantation in the testis. RESULTS: Supplementation with FSH in cell culture increased the number of cSSCs positive for GFRA1. The cSSCs were also positive for the pluripotency and early germline marker OCT4 and the late germline markers PLZF, DAZL, C-kit, and GFRA-1. The in vivo experiments showed that the cSSCs xenotransplanted into infertile mouse testes were able to repopulate germline cells in the seminiferous tubules of mice. CONCLUSIONS: In conclusion, our results showed for the first time that the treatment of cSSC cultures with FSH can promote in vitro self-renewal, increase the population of germline cells, and possibly influence the success of spermatogenesis in infertile mice in vivo.

Biomaterials ; 210: 12-24, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31048198


In the past decade, calcium phosphate (CaP) ceramics have emerged as alternatives to autologous bone grafts for the treatment of large, critical-sized bone defects. In order to be effective in the regeneration of such defects, ceramics must show osteoinductive behaviour, defined as the ability to induce de novo heterotopic bone formation. While a set of osteoinductive CaP ceramics has been developed, the exact processes underlying osteoinduction, and the role of the physical and chemical properties of the ceramics, remain largely unknown. Previous studies have focused on the role of the transcriptome to shed light on the mechanism of osteoinduction at the mRNA level. To complement these studies, a proteomic analysis was performed to study the behaviour of hMSCs on osteoinductive and non-osteoinductive CaPs. The results of this analysis suggest that plasma cell glycoprotein 1 (PC-1), encoded by the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, plays a key role in the process of osteoinduction by CaP ceramics. Validation experiments have confirmed that indeed, the mRNA expression of ENPP1 and the production of PC-1 are higher on osteoinductive than on non-osteoinductive CaP ceramics, a trend that was also observed for other osteogenic markers such as bone morphogenetic protein 2 (BMP2) and osteopontin (OPN), but not for alkaline phosphatase (ALP). Our results also showed that the expression of PC-1 is restricted to those cells which are in direct contact with the CaP ceramic surface, plausibly due to the localised depletion of calcium and inorganic phosphate ions from the supersaturated cell culture medium as CaP crystallises on the ceramic surface. Replicating the surface of the osteoinductive ceramic in polystyrene resulted in a significant decrease in ENPP1 expression, suggesting that surface structural properties alone are not sufficient to induce ENPP1 expression. Finally, knocking down ENPP1 expression in hMSCs resulted in increased BMP2 expression, both at the mRNA and protein level, suggesting that ENPP1 is a negative regulator of BMP-2 signalling. Taken together, this study shows, for the first time, that ENPP1/PC-1 plays an important role in CaP-induced osteogenic differentiation of hMSCs and thus possibly osteoinduction by CaP ceramics. Furthermore, we have identified a crucial role for the interfacial (chemical) events occurring on the CaP ceramic surface in the process of osteoinduction. This knowledge can contribute to the development of new bone graft substitutes, with improved osteoinductive potential.

J Neurophysiol ; 121(6): 2267-2275, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31017845


If the brain abstractly represents probability distributions as knowledge, then the modality of a decision, e.g., movement vs. perception, should not matter. If, on the other hand, learned representations are policies, they may be specific to the task where learning takes place. Here, we test this by asking whether a learned spatial prior generalizes from a sensorimotor estimation task to a two-alternative-forced choice (2-Afc) perceptual comparison task. A model and simulation-based analysis revealed that while participants learn prior distribution in the sensorimotor estimation task, measured priors are consistently broader than sensorimotor priors in the 2-Afc task. That the prior does not fully generalize suggests that sensorimotor priors are more like policies than knowledge. In disagreement with standard Bayesian thought, the modality of the decision has a strong influence on the implied prior distributions. NEW & NOTEWORTHY We do not know whether the brain represents abstract and generalizable knowledge or task-specific policies that map internal states to actions. We find that learning in a sensorimotor task does not generalize strongly to a perceptual task, suggesting that humans learned policies and did not truly acquire knowledge. Priors differ across tasks, thus casting doubt on the central tenet of many Bayesian models, that the brain's representation of the world is built on generalizable knowledge.

Nat Commun ; 10(1): 1817, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000720


Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's disease manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances the clearance of such proteins and ameliorates their toxicities in animal models, we and others have sought to re-position/re-profile existing compounds used in humans to identify those that may induce autophagy in the brain. A key challenge with this approach is to assess if any hits identified can induce neuronal autophagy at concentrations that would be seen in humans taking the drug for its conventional indication. Here we report that felodipine, an L-type calcium channel blocker and anti-hypertensive drug, induces autophagy and clears diverse aggregate-prone, neurodegenerative disease-associated proteins. Felodipine can clear mutant α-synuclein in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug. This is associated with neuroprotection in mice, suggesting the promise of this compound for use in neurodegeneration.

Autofagia/efeitos dos fármacos , Reposicionamento de Medicamentos , Felodipino/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Animais , Animais Geneticamente Modificados , Linhagem Celular , Córtex Cerebral/citologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Embrião de Mamíferos , Embrião não Mamífero , Felodipino/uso terapêutico , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Cultura Primária de Células , Suínos , Porco Miniatura , Resultado do Tratamento , Peixe-Zebra , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
Hum Mol Genet ; 28(12): 2001-2013, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30753527


Parkinson's disease (PD) is the second most common neurodegenerative disorder and a central role for α-synuclein (αSyn; SNCA) in disease aetiology has been proposed based on genetics and neuropathology. To better understand the pathological mechanisms of αSyn, we generated induced pluripotent stem cells (iPSCs) from healthy individuals and PD patients carrying the A53T SNCA mutation or a triplication of the SNCA locus and differentiated them into dopaminergic neurons (DAns). iPSC-derived DAn from PD patients carrying either mutation showed increased intracellular αSyn accumulation, and DAns from patients carrying the SNCA triplication displayed oligomeric αSyn pathology and elevated αSyn extracellular release. Transcriptomic analysis of purified DAns revealed perturbations in expression of genes linked to mitochondrial function, consistent with observed reduction in mitochondrial respiration, impairment in mitochondrial membrane potential, aberrant mitochondrial morphology and decreased levels of phosphorylated DRP1Ser616. Parkinson's iPSC-derived DAns showed increased endoplasmic reticulum stress and impairments in cholesterol and lipid homeostasis. Together, these data show a correlation between αSyn cellular pathology and deficits in metabolic and cellular bioenergetics in the pathology of PD.

Rev Bras Enferm ; 71(suppl 6): 2854-2857, 2018.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30540067


OBJECTIVE: To reflect on technologies for the peace culture that can be used in family nursing. METHOD: Theoretical essay, based on the premises of non-violence and peace culture. RESULTS: Four light technologies are singled out for the peace culture within families: nonviolent communication, qualified listening, conflict mediation, and restorative circles. CONCLUSION: The technologies proposed can be used by nurses to promote care and policies aiming at a peace culture and non-violence in families, with the objective of assisting in the obtainment of the well-being for family systems and their correlations.

Saúde da Família/tendências , Cuidados de Enfermagem/métodos , Violência/prevenção & controle , Comunicação , Humanos , Violência/psicologia
Rev Bras Enferm ; 71(5): 2599-2601, 2018 Sep-Oct.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30304196


OBJECTIVE: To present a reflection on the forms of violence in health care settings and on preventive actions. METHOD: This is a theoretical reflection about the phenomenon of violence and its possible coping actions. RESULTS: Nurses and other professionals working in health care environments may experience situations of aggression and disrespect through institutional or managerial violence, horizontal violence and patient violence. FINAL CONSIDERATIONS: Violent practices are not applicable in any workplace, especially in care settings. Actions or measures of control should be taken in pursuit of healthier environments and in harmony with the culture of peace.

Rev. bras. enferm ; 71(5): 2599-2601, Sep.-Oct. 2018.
Artigo em Inglês | LILACS-Express | ID: biblio-958706


ABSTRACT Objective: To present a reflection on the forms of violence in health care settings and on preventive actions. Method: This is a theoretical reflection about the phenomenon of violence and its possible coping actions. Results: Nurses and other professionals working in health care environments may experience situations of aggression and disrespect through institutional or managerial violence, horizontal violence and patient violence. Final considerations: Violent practices are not applicable in any workplace, especially in care settings. Actions or measures of control should be taken in pursuit of healthier environments and in harmony with the culture of peace.

RESUMEN Objetivo: Presentar reflexión sobre las formas de violencia en ambientes de atención a la salud y sobre las acciones para prevención. Método: Es una reflexión teórica acerca del fenómeno de la violencia y sus posibles acciones de enfrentamiento. Resultados: Enfermeros y otros profesionales que actúan en ambientes de cuidado a la salud pueden experimentar situaciones de agresión y falta de respeto a través de la violencia institucional o gerencial, la violencia horizontal y la violencia de los pacientes. Consideraciones finales: Las prácticas violentas no se aceptan en cualquier lugar de trabajo, especialmente en ambientes destinados al cuidado. Las acciones o medidas de control deben ser adoptadas en busca de ambientes más saludables y en consonancia con la cultura de paz.

Resumo Objetivo: Apresentar reflexão sobre as formas de violência em ambientes de cuidados à saúde e sobre as ações para prevenção. Método: Trata-se de uma reflexão teórica acerca do fenômeno da violência e suas possíveis ações de enfrentamento. Resultados: Enfermeiros e outros profissionais que atuam em ambientes de cuidado à saúde podem vivenciar situações de agressão e desrespeito por meio da violência institucional ou gerencial, da violência horizontal e da violência dos pacientes. Considerações finais: As práticas violentas não são cabíveis em quaisquer locais de trabalho, especialmente em ambientes destinados ao cuidado. Ações ou medidas de controle devem ser adotadas em busca de ambientes mais saudáveis e em consonância com a cultura de paz.

Front Comput Neurosci ; 12: 56, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30072887


Neuroscience has long focused on finding encoding models that effectively ask "what predicts neural spiking?" and generalized linear models (GLMs) are a typical approach. It is often unknown how much of explainable neural activity is captured, or missed, when fitting a model. Here we compared the predictive performance of simple models to three leading machine learning methods: feedforward neural networks, gradient boosted trees (using XGBoost), and stacked ensembles that combine the predictions of several methods. We predicted spike counts in macaque motor (M1) and somatosensory (S1) cortices from standard representations of reaching kinematics, and in rat hippocampal cells from open field location and orientation. Of these methods, XGBoost and the ensemble consistently produced more accurate spike rate predictions and were less sensitive to the preprocessing of features. These methods can thus be applied quickly to detect if feature sets relate to neural activity in a manner not captured by simpler methods. Encoding models built with a machine learning approach accurately predict spike rates and can offer meaningful benchmarks for simpler models.

Am J Sports Med ; 46(12): 2905-2914, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30074814


BACKGROUND: The anterior cruciate ligament (ACL) has poor regenerative capacity, and an injury leads to loss of function, limiting quality of life and increasing the incidence of osteoarthritis. Surgical interventions can stabilize the joint and improve functional recovery. The delivery of growth factors (GFs) enhances the healing process; however, this is complex in its regulation, is high in costs, has side effects, and can only be accomplished with supraphysiological concentrations and thus is currently not clinically feasible. However, the immobilization of a patient's endogenous GFs in biomaterials can overcome these problems. PURPOSE: To develop a method to capture endogenous bone morphogenetic protein-2 (BMP-2) and ultimately show enhanced ACL healing in vivo using this novel methodology. STUDY DESIGN: Controlled laboratory study. METHODS: BMP-2 binding peptides were synthetized, purified, and immobilized on polycaprolactone (PCL) films. The affinity between the peptide and human BMP-2 (hBMP-2) was confirmed with immunofluorescence and enzyme-linked immunosorbent assay. The C2C12 Luc reporter cell line was used to confirm the bioactivity of immobilized BMP-2. For in vivo experiments, the same functionalization technology was applied to the commercially available Polytape, and the functionalized tape was sutured together with the graft used for ACL reconstruction in rats. Each animal underwent reconstruction with either native Polytape (n = 3) or Polytape with BMP-2 binding peptides (n = 3). At 2 and 6 weeks after surgery, the graft was assessed by histology and micro-computed tomography. RESULTS: The covalent immobilization of the peptide in PCL was successful, allowing the peptide to capture hBMP-2, which remained bioactive and led to the osteogenic differentiation of C2C12. In vivo experiments confirmed the potential of the Polytape functionalized with the BMP-2 binding peptide to capture endogenous BMP-2, leading to enhanced bone formation inside the femoral and tibial tunnels and ultimately improving the graft's quality. CONCLUSION: The incorporation of BMP-2 binding peptides into materials used for ACL reconstruction can capture endogenous hBMP-2, which enhances the healing process inside the bone tunnels. CLINICAL RELEVANCE: These results demonstrate the potential of using synthetic peptides to endow biomaterials with novel biological functions, namely to capture and immobilize endogenous GFs.

Biofabrication ; 10(4): 045005, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30024388


The fabrication of bioactive scaffolds able to mimic the in vivo cellular microenvironment is a challenge for regenerative medicine. The creation of sites for the selective binding of specific endogenous proteins represents an attractive strategy to fabricate scaffolds able to elicit specific cell response. Here, electrospinning (ESP) and soft-molecular imprinting (soft-MI) techniques were combined to fabricate a soft-molecular imprinted electrospun bioactive scaffold (SMIES) for tissue regeneration. Scaffolds functionalized using different proteins and growth factors (GFs) arranged onto the surface were designed, fabricated and validated with different polyesters, demonstrating the versatility of the developed approach. The scaffolds bound selectively each of the different proteins used, indicating that the soft-MI method allowed fabricating high affinity binding sites on ESP fibers compared to non-imprinted ones. The imprinting of ESP fibers with several GFs resulted in a significant effect on cell behavior. FGF-2 imprinted SMIES promoted cell proliferation and metabolic activity. BMP-2 and TGF-ß3 imprinted SMIES promoted cellular differentiation. These scaffolds hold the potential to be used in a cell-free approach to steer endogenous tissue regeneration in several regenerative medicine applications.

Pharmacology ; 101(5-6): 290-297, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29587275


BACKGROUND/AIMS: Several guidelines for neuropathic pain management and various effective drugs are available; however, neuropathic pain remains undertreated. This retrospective study aimed to evaluate the efficacy of topical capsaicin 8% in peripheral neuropathic pain in a routine clinical setting. METHODS: Therapeutic efficacy was evaluated through pain intensity, using numerical pain rating scale at baseline and 7-14 days after each treatment, and using pain treatment area (PTA) assessed immediately before each treatment. RESULTS: A total of 43 patients with either post-herpetic neuralgia or post-traumatic/post-surgical neuropathic pain were enrolled. The median percentage reduction in numerical pain rating scale score and in PTA was -40.0 (-50.0 to -33.3; 95% CI, bootstrap) and -35.1 (-50.9 to 3.4; 95% CI, bootstrap), respectively. Pain intensity and PTA were equally improved and reduced in both treated conditions. CONCLUSION: This study suggests that topical capsaicin 8% reduces peripheral neuropathic pain as well as treatment pain area.

Capsaicina/administração & dosagem , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia/tratamento farmacológico , Fármacos do Sistema Sensorial/administração & dosagem , Administração Cutânea , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Adesivo Transdérmico , Resultado do Tratamento