RESUMO
BACKGROUND: When commencing enteral feeding, patients and families will want to know the likelihood of returning to an oral diet. There is a paucity of data on the prognosis of patients with gastrostomies. We describe a large dataset of patients, which identifies factors influencing gastrostomy removal and assesses the likelihood of the patient having at home enteral nutrition. METHODS: Retrospective data was collected on patients from Sheffield Teaching Hospitals who had received a gastrostomy and had outpatient enteral feeding between January 2016 and December 2019. Demographic data, indication and outcomes were analysed. RESULTS: A total of 451 patients were assessed, median age: 67.7. 183/451(40.6%) gastrostomies were for head and neck cancer, 88/451 (19.5%) for stroke, 28/451 (6.2%) for Motor Neuron Disease, 32/451 (7.1%) for other neurodegenerative causes, 120/451 (26.6%) other. Of the 31.2% who had their gastrostomy removed within 3 years, head and neck cancer was the most common indication (58.3%) followed by stroke (10.2%), Motor Neuron Disease (7.1%) and other neurodegenerative diseases (3.1%). Gastrostomy removal was significantly influenced by age, place of residence, and having head and neck cancer (p < 0.05). There was the greatest likelihood of removal within the first year (24%). 70.5% had enteral feeding at home. CONCLUSION: This large cohort study demonstrates 31.2% of patients had their gastrostomy removed within 3 years. Head and neck cancer patients, younger age and residing at home can help positively predict removal. Most patients manage their feeding at home rather than a nursing home. This study provides new information on gastrostomy outcomes when counselling patients to provide realistic expectations.
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Remoção de Dispositivo , Nutrição Enteral , Gastrostomia , Humanos , Gastrostomia/estatística & dados numéricos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Nutrição Enteral/estatística & dados numéricos , Pessoa de Meia-Idade , Remoção de Dispositivo/estatística & dados numéricos , Idoso de 80 Anos ou mais , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/terapia , Acidente Vascular Cerebral , Doença dos Neurônios Motores/terapia , Adulto , Doenças Neurodegenerativas/terapiaRESUMO
BACKGROUND: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non-invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions. METHODS: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis. FINDINGS: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision-making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision-making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change. CONCLUSION: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation. PATIENT OR PUBLIC CONTRIBUTION: The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs).
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Gastrostomia , Doença dos Neurônios Motores , Humanos , Gastrostomia/psicologia , Qualidade de Vida , Doença dos Neurônios Motores/terapia , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/psicologia , Pessoal de Saúde , Cuidadores/psicologiaRESUMO
Lactate levels are commonly used as an indirect measure to assess metabolic stress in clinical conditions like sepsis. Dynamic lactate measurements are recommended to assess and guide treatment in patients with shock and other critical care conditions. A minimally invasive, continuous lactate monitor has potential to improve clinical decisions and patient care. The purpose of the study was to evaluate continuous lactate measurements of a novel enzymatic Continuous Lactate Monitor (CLM) developed in our laboratory. Lactate levels were monitored during incremental cycling exercise challenges as a tool for hyperlactatemia. Six healthy individuals 18-45 y/o (4 males, 2 females) participated in the study. CLM devices were inserted subcutaneously in the postero-lateral trunk below the renal angle, one hour before the exercise challenge. Each exercise challenge consisted of a 3 to 12-min warm up period, followed by up to 7, 4-min incremental workload bouts separated by rest intervals. Continuous lactate measurements obtained from CLM were compared with commercial lactate analyzer (Abbott iSTAT) measurements of venous blood (plasma) drawn from the antecubital vein. Blood was drawn at up to 25 time points spanning the duration of before exercise, during exercise, and up to 120 min post exercise. Area under the curve (AUC), and delay time were calculated to compare the CLM readings with plasma lactate concentration. Average plasma lactate concentration increased from 1.02 to 16.21 mM. Ratio of AUC derived from CLM to plasma lactate was 1.025 (0.990-1.058). Average dynamic delay time of CLM to venous plasma lactate was 5.22 min (2.87-10.35). Insertion sites examined 48 h after CLM removal did not show signs of side effects and none required medical attention upon examination. The newly developed CLM has shown to be a promising tool to continuously measure lactate concentration in a minimally invasive fashion. Results indicate the CLM can provide needed trends in lactate over time. Such a device may be used in the future to improve treatment in clinical conditions such as sepsis.
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Sepse , Choque , Cuidados Críticos , Feminino , Humanos , Ácido Láctico , Masculino , Monitorização FisiológicaRESUMO
Copy-number variations (CNVs) are strong risk factors for neurodevelopmental and psychiatric disorders. The 15q13.3 microdeletion syndrome region contains up to ten genes and is associated with numerous conditions, including autism spectrum disorder (ASD), epilepsy, schizophrenia, and intellectual disability; however, the mechanisms underlying the pathogenesis of 15q13.3 microdeletion syndrome remain unknown. We combined whole-genome sequencing, human brain gene expression (proteome and transcriptome), and a mouse model with a syntenic heterozygous deletion (Df(h15q13)/+ mice) and determined that the microdeletion results in abnormal development of cortical dendritic spines and dendrite outgrowth. Analysis of large-scale genomic, transcriptomic, and proteomic data identified OTUD7A as a critical gene for brain function. OTUD7A was found to localize to dendritic and spine compartments in cortical neurons, and its reduced levels in Df(h15q13)/+ cortical neurons contributed to the dendritic spine and dendrite outgrowth deficits. Our results reveal OTUD7A as a major regulatory gene for 15q13.3 microdeletion syndrome phenotypes that contribute to the disease mechanism through abnormal cortical neuron morphological development.
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Transtornos Cromossômicos/enzimologia , Transtornos Cromossômicos/genética , Enzimas Desubiquitinantes/fisiologia , Endopeptidases/genética , Deficiência Intelectual/enzimologia , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Convulsões/enzimologia , Convulsões/genética , Animais , Transtorno do Espectro Autista/genética , Deleção Cromossômica , Cromossomos Humanos Par 15/enzimologia , Cromossomos Humanos Par 15/genética , Espinhas Dendríticas/metabolismo , Enzimas Desubiquitinantes/genética , Endopeptidases/metabolismo , Feminino , Deleção de Genes , Estudos de Associação Genética , Humanos , Masculino , Camundongos , Fenótipo , Prosencéfalo/patologiaRESUMO
PURPOSE: To evaluate the feasibility of a new optical device that measures peripheral blood flow as a diagnostic and monitoring tool for patients with peripheral artery disease (PAD). MATERIALS AND METHODS: In this prospective study, 167 limbs of 90 patients (mean age, 76 y; 53% men) with suspected PAD were evaluated with the FlowMet device, which uses a new type of dynamic light-scattering technology to assess blood flow in real time. Measurements of magnitude and phasicity of blood flow were combined into a single-value flow-waveform score and compared vs ankle-brachial index (ABI), toe-brachial index (TBI), and clinical presentation of patients per Rutherford category (RC). Receiver operating characteristic curves were constructed to predict RC. Area under the curve (AUC), sensitivity, and specificity were compared among flow-waveform score, ABI, and TBI. RESULTS: Qualitatively, the FlowMet waveforms were analogous to Doppler velocity measurements, and degradation of waveform phasicity and amplitude were observed with increasing PAD severity. Quantitatively, the flow, waveform, and composite flow-waveform scores decreased significantly with decreasing TBI. In predicting RC ≥ 4, the flow-waveform score (AUC = 0.83) showed a linear decrease with worsening patient symptoms and power comparable to that of TBI (AUC = 0.82) and better than that of ABI (AUC = 0.71). Optimal sensitivity and specificity pairs were found to be 56%/83%, 72%/81%, and 89%/74% for ABI, TBI, and flow-waveform score, respectively. CONCLUSIONS: The technology tested in this pilot study showed a high predictive value for diagnosis of critical limb ischemia. The device showed promise as a diagnostic tool capable of providing clinical feedback in real time.
Assuntos
Técnicas de Diagnóstico Cardiovascular/instrumentação , Isquemia/diagnóstico , Doença Arterial Periférica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Velocidade do Fluxo Sanguíneo , Estado Terminal , Estudos Transversais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Isquemia/fisiopatologia , Luz , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Espalhamento de Radiação , Índice de Gravidade de DoençaRESUMO
BACKGROUND: People living with amyotrophic lateral sclerosis (ALS) face many challenges with respect to taking adequate nutrition. Growing evidence links weight loss with negative prognostic outcomes. We aimed to explore the practice of dietitians in the UK with regard to the nutritional management of ALS. METHODS: A national online survey was disseminated via professional groups, social media and newsletters to UK healthcare professionals between September and November 2018. The survey examined the nutritional management of ALS. Dietitian responses are reported in the present study. RESULTS: In total, 130 dietitians responded to the survey. Two-thirds reported that ALS comprised less than 20% of their total patient caseload. Forty-two percent reported that nutritional screening took place in their organisation. One-half of dietitians reported that patients were referred for dietetic assessment at 'about the right time', although 44% reported referrals were made too late. The majority (83%) of dietitians used resting energy expenditure predictive equations not validated in ALS. When setting weight goals, dietitians reported most frequently recommending weight maintenance if the patient's body mass index was 18.5-25 kg m-2 (72%), 25-30 kg m-2 (98%), and > 30 kg m-2 (79%). In addition, 43% reported that people with ALS were not weighed sufficiently frequently. CONCLUSIONS: Although the importance of early nutritional assessment is recognised, the timeliness of dietetic input and on-going monitoring of nutritional status in ALS care might not currently be ideal. Dietitians report using energy requirement predictive equations and setting weight goals that may not promote positive outcomes. Further research is required to understand the optimal nutritional management of ALS.
Assuntos
Esclerose Lateral Amiotrófica , Desnutrição , Nutricionistas , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Avaliação Nutricional , Estado NutricionalRESUMO
Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.
Assuntos
Transtorno do Espectro Autista/metabolismo , Transtornos do Neurodesenvolvimento/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Adulto , Animais , Ansiedade/genética , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/psicologia , Criança , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Dendritos/metabolismo , Dendritos/patologia , Feminino , Humanos , Relações Interpessoais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Transtornos do Neurodesenvolvimento/psicologia , Neurogênese , Fenótipo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Transmissão Sináptica , Sequenciamento do ExomaRESUMO
Anecdotal evidence suggests the use of bolus tube feeding is increasing in the long-term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from ten centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding (n 604, 60 % male, age 58 years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients' complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37 %). Patients were long-term tube fed (4·1 years tube feeding, 3·5 years bolus tube feeding), living at home (71 %) and sedentary (70 %). The majority were head and neck cancer patients (22 %) who were significantly more active (79 %) and lived at home (97 %), while those with cerebral palsy (12 %) were typically younger (age 31 years) but sedentary (94 %). Most patients used bolus feeding as their sole feeding method (46 %), because it was quick and easy to use, as a top-up to oral diet or to mimic mealtimes. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85 % of patients, with 51 % of these being compact-style ONS (2·4 kcal (10·0 kJ)/ml, 125 ml). This survey shows that bolus tube feeding is common among UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.
Assuntos
Nutrição Enteral/métodos , Nutrição Enteral/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Paralisia Cerebral/terapia , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
The feasibility of integrating remote presence technology within a simulation scenario for psychiatric-mental health nursing (PMHN) students to develop telehealth competencies was evaluated. A wireless, audiovisual robot from Double® Robotics, maneuverable by smartphone or tablet computer, was used to simulate the facilitation of students' patient assessment and treatment decisions from a distant location for 32 weeks (total hours of robotic simulation = 32). Qualitative data were collected to assess student and faculty satisfaction, as well as for feasibility evaluations. Overall, students participating in the telehealth-enabled simulations reported moderate (9 of 36 students) to strong (25 of 36 students) value for the use of telemedicine within the simulation in a 3-point Likert scale post-simulation survey. These results illustrate the feasibility of using a remote presence robot in an educational simulation environment. Remote presence in clinical simulations can contribute to workforce preparation to apply telehealth-enabled communication in PMHN settings. [Journal of Psychosocial Nursing and Mental Health Services, 57(7), 23-28.].
Assuntos
Educação a Distância , Educação em Enfermagem , Simulação de Paciente , Enfermagem Psiquiátrica/educação , Robótica , Telemedicina , Humanos , Modelos Educacionais , Pesquisa Qualitativa , Estudantes de EnfermagemRESUMO
A Ni-catalyzed method for arylboration is disclosed. The method allows for highly stereoselective arylboration of unactivated alkenes. The reactions utilize a simple Ni-catalyst and work with a broad range of alkenes and aryl bromides. The products represent useful intermediates for chemical synthesis due to the versatility of the C-B bond. Preliminary mechanistic details of the method are also disclosed.
Assuntos
Alcenos/química , Compostos de Boro/síntese química , Níquel/química , Compostos de Boro/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
CcaA is a ß-carbonic anhydrase (CA) that is a component of the carboxysomes of a subset of ß-cyanobacteria. This protein, which has a characteristic C-terminal extension of unknown function, is recruited to the carboxysome via interactions with CcmM, which is itself a γ-CA homolog with enzymatic activity in many, but not all cyanobacteria. We have determined the structure of CcaA from Synechocystis sp. PCC 6803 at 1.45â Å. In contrast with the dimer-of-dimers organization of most bacterial ß-CAs, or the loose dimer-of-dimers-of-dimers organization found in the plant enzymes, CcaA shows a well-packed trimer-of-dimers organization. The proximal part of the characteristic C-terminal extension is ordered by binding at a site that passes through the two-fold symmetry axis shared with an adjacent dimer; as a result, only one of a pair of converging termini can be ordered at any given time. Docking in Rosetta failed to find well-packed solutions, indicating that formation of the CcaA/CcmM complex probably requires significant backbone movements in at least one of the binding partners. Surface plasmon resonance experiments showed that CcaA forms a complex with CcmM with sub-picomolar affinity, with contributions from residues in CcmM's αA helix and CcaA's C-terminal tail. Catalytic characterization showed CcaA to be among the least active ß-CAs characterized to date, with activity comparable with the γ-CA, CcmM, it either complements or replaces. Intriguingly, the C-terminal tail appears to partly inhibit activity, possibly indicating a role in minimizing the activity of unencapsulated enzyme.
Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Anidrases Carbônicas/química , Anidrases Carbônicas/metabolismo , Synechococcus/enzimologia , Sequência de Aminoácidos , Cristalografia por Raios X , Cinética , Dados de Sequência Molecular , Multimerização Proteica , Ressonância de Plasmônio de SuperfícieRESUMO
BACKGROUND AND OBJECTIVE: Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters. STUDY DESIGN/MATERIALS AND METHODS: We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm2 . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining. RESULTS: TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm2 light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm2 , epidermal damage was noted with vascular injury. At light doses >50 J/cm2 , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm2 light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear. CONCLUSION: TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Lasers Semicondutores/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Animais , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Mancha Vinho do Porto/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPßS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K(+) with Cs(+) Consistent with an underlying mechanism of direct inhibition of one or more K(+) channels, nicotine was found to rapidly reduce the fast-inactivating A-type K(+) current as well as both components of the delayed-rectifier K(+) current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K(+) channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Neurônios/metabolismo , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Animais , Aplysia , Células Cultivadas , Césio/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismoRESUMO
Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.
RESUMO
BACKGROUND AND OBJECTIVE: Nanotechnology offers the possibility of creating multi-functional structures that can provide solutions for biomedical problems. The nanoprobes herein described are an example of such structures, where nano-scaled particles have been designed to provide high specificity and contrast potential for optical detection of cancer. Specifically, enzymatically activated fluorescent nanoprobes (EANPs) were synthesized as cancer-specific contrast agents for optical imaging. STUDY DESIGN/MATERIALS AND METHODS: EANPs were prepared by nanoprecipitation of blends of poly(lactic acid)-b-poly(ethylene glycol) and poly(lactic-co-glycolic acid)-b-poly(l-lysine). The lysine moieties were then covalently decorated with the near infrared (NIR) fluorescent molecule AlexaFluor-750 (AF750). Close proximity of the fluorescent molecules to each other resulted in fluorescence quenching, which was reversed by enzymatically mediated cleavage of poly(l-lysine) chains. EANPs were characterized by dynamic light scattering and electron microscopy. Enzymatic development of fluorescence was studied in vitro by fluorescence spectroscopy. Biocompatibility and contrast potential of EANPs were studied in cancerous and noncancerous cells. The potential of the nanoprobes as contrast agents for NIR fluorescence imaging was studied in tissue phantoms. RESULTS: Spherical EANPs of â¼100 nm were synthesized via nanoprecipitation of polymer blends. Fluorescence activation of EANPs by treatment with a model protease was demonstrated with up to 15-fold optical signal enhancement within 120 minutes. Studies with MDA-MB-231 breast cancer cells demonstrated the cytocompatibility of EANPs, as well as enhanced fluorescence associated with enzymatic activation. Imaging studies in tissue phantoms confirmed the ability of a simple imaging system based on a laser source and CCD camera to image dilute suspensions of the nanoprobe at depths of up to 4 mm, as well as up to a 13-fold signal-to-background ratio for enzymatically activated EANPs compared to un-activated EANPs at the same concentration. CONCLUSION: Nanoprecipitation of copolymer blends containing poly(l-lysine) was utilized as a method for preparation of highly functional nanoprobes with high potential as contrast agents for fluorescence based imaging of cancer. Lasers Surg. Med. 47:579-594, 2015. © 2015 Wiley Periodicals, Inc.
RESUMO
Nicotinic receptors form a diverse group of ligand-gated ionotropic receptors with roles in both synaptic transmission and the control of excitability. In the bag cell neurons of Aplysia, acetylcholine activates an ionotropic receptor, which passes inward current to produce a long-lasting afterdischarge and hormone release, leading to reproduction. While testing the agonist profile of the cholinergic response, we observed a second current that appeared to be gated only by nicotine and not acetylcholine. The peak nicotine-evoked current was markedly smaller in magnitude than the acetylcholine-induced current, cooperative (Hill value of 2.7), had an EC50 near 500 µM, readily recovered from desensitization, showed Ca(2+) permeability, and was blocked by mecamylamine, dihydro-ß-erythroidine, or strychnine, but not by α-conotoxin ImI, methyllycaconitine, or hexamethonium. Aplysia transcriptome analysis followed by PCR yielded 20 full-length potential nicotinic receptor subunits. Sixteen of these were predicted to be cation selective, and real-time PCR suggested that 15 of the 16 subunits were expressed to varying degrees in the bag cell neurons. The acetylcholine-induced current, but not the nicotine current, was reduced by double-strand RNA treatment targeted to both subunits ApAChR-C and -E. Conversely, the nicotine-evoked current, but not the acetylcholine current, was lessened by targeting both subunits ApAChR-H and -P. To the best of our knowledge, this is the first report suggesting that a nicotinic receptor is not gated by acetylcholine. Separate receptors may serve as a means to differentially trigger plasticity or safeguard propagation by assuring that only acetylcholine, the endogenous agonist, initiates large enough responses to trigger reproduction.
Assuntos
Potenciais de Ação , Células Neuroendócrinas/metabolismo , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Acetilcolina/farmacologia , Aconitina/análogos & derivados , Aconitina/farmacologia , Animais , Aplysia , Conotoxinas/farmacologia , Di-Hidro-beta-Eritroidina/farmacologia , Hexametônio/farmacologia , Mecamilamina/farmacologia , Células Neuroendócrinas/efeitos dos fármacos , Células Neuroendócrinas/fisiologia , Nicotina/farmacologia , Receptores Nicotínicos/genética , Estricnina/farmacologia , TranscriptomaRESUMO
OBJECTIVE: Understand the practice and beliefs of healthcare professionals (HCPs) supporting the decision-making of people with MND (pwMND) about gastrostomy placement, including identifying differences between professions. METHODS: An online cross-sectional survey disseminated to HCPs who support the decision-making of pwMND about gastrostomy placement. RESULTS: A total of 139 participants completed the survey including representation from a range of healthcare professions. A third (36/101, 36%) initiated discussions about gastrostomy later in practice than they believed was ideal. In relation to the outcome of declining compared to accepting gastrostomy, participants were more likely to discuss aspiration (80% vs. 68%), choking (76% vs. 58%) and prognosis (36% vs. 22%). Participants believed gastrostomies should be placed after a mean 8.1% weight loss since symptom-onset. More participants favored gastrostomy placement before pwMND presented with respiratory symptoms (45%) compared to onset of dysphagia (11%). Half believed pwMND placed gastrostomies too late. Participants were more likely to 'often'/'always' recommend pwMND to have a gastrostomy (23%) than continue without (7%) or decline (4%) gastrostomy, when believing these were the best option for pwMND. Nurses and dietitians discussed the broadest range of information, while doctors were more likely to discuss mortality risk and prognosis. CONCLUSION: There is variation in HCPs practice and beliefs about initiating discussions, the sharing of information and recommendations, and timing, about gastrostomy placement. The information shared varies by profession and there is evidence of sub-optimal communication between HCPs. Further research is required to understand how these findings may impact on the decision-making of pwMND about gastrostomy.
Assuntos
Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Humanos , Gastrostomia , Estudos Transversais , Doença dos Neurônios Motores/cirurgia , Reino Unido , Atenção à SaúdeRESUMO
BACKGROUND: Enteral tube feeding can require considerable amounts of plastic equipment including delivery sets and containers, often disposed of after a single feeding session because of bacterial contamination concerns. The aim of this research was to assess whether reuse of delivery sets and containers for up to 24 h is safe from a microbiological perspective. METHODS: Four enteral tube feeding systems (FS) were tested under hygienic controlled or repeated inoculation challenge conditions using key foodborne pathogens, to assess bacterial growth over time (FS1: ready-to-hang, closed 1-L system with delivery set reused, stored at room temperature [RT]; FS2: a prepared, powdered, open 1-L system with delivery set and container reused, stored at RT; FS3 and FS4: prepared, powdered, open 200-ml bolus systems with delivery set and container reused, stored at RT [FS3] and refrigeration [FS4]). Feed samples were cultured at 0.5, 6.5, 12.5, 18.5, and 24.5 h with >2 Δlog considered significant bacterial growth. RESULTS: Under hygienic control, FS1, FS3, and FS4 were below the level of enumeration (<5 CFU/g) for all bacteria tested, at all time points. In FS2, significant bacterial growth was observed from 18.5 h. Under repeated bacterial inoculation challenge, no significant growth was observed in FS1 and FS4 over 24.5 h; however, significant growth was observed in FS2 after 6.5 h and in FS3 after 10-12 h. CONCLUSION: With hygienic handling technique, there is limited bacterial growth with reuse of delivery sets and containers over 24 h. Refrigeration between feeding sessions and using boluses of reconstituted powdered feed reduce bacterial growth risk.
Assuntos
Nutrição Enteral , Contaminação de Equipamentos , Humanos , Nutrição Enteral/métodos , Contaminação de Equipamentos/prevenção & controle , Bactérias , Refrigeração , Microbiologia de AlimentosRESUMO
OBJECTIVES: Research suggests that higher Body Mass Index is associated with improved survival in people with Amyotrophic Lateral Sclerosis (pwALS). Yet, understanding of the barriers and enablers to increasing calorie intake is limited. This study sought to explore these issues from the perspective of pwALS, informal carers, and healthcare professionals. METHODS: Interviews with 18 pwALS and 16 informal carers, and focus groups with 51 healthcare professionals. Data were analysed using template analysis and mapped to the COM-B model and Theoretical Domains Framework (TDF). RESULTS: All three COM-B components (Capability, Opportunity and Motivation) are important to achieving high calorie diets in pwALS. Eleven TDF domains were identified: Physical skills (ALS symptoms); Knowledge (about high calorie diets and healthy eating); Memory, attention, and decision processes (reflecting cognitive difficulties); Environmental context/resources (availability of informal and formal carers); Social influences (social aspects of eating); Beliefs about consequences (healthy eating vs. high calorie diets); Identity (interest in health lifestyles); Goals (sense of control); Reinforcement (eating habits); and Optimism and Emotion (low mood, poor appetite). DISCUSSION: To promote high calorie diets for pwALS, greater clarity around the rationale and content of recommended diets is needed. Interventions should be tailored to patient symptoms, preferences, motivations, and opportunities.
Assuntos
Esclerose Lateral Amiotrófica , Cuidadores , Humanos , Pessoal de Saúde/psicologia , Ingestão de Energia , Atenção à Saúde , Pesquisa QualitativaRESUMO
Background: Significant morbidity and mortality can be associated with gastrostomy insertion, likely influenced by patient selection, indication and aftercare. We aimed to establish what current variation in practice exists and how this has improved by comparison to our previously published British Society of Gastroenterology survey of 2010. Methods: We approached all National Health Service (NHS) hospitals in England (n=198). Email and web-based questionnaires were circulated. These data were correlated with the National Endoscopy Database (NED). Results: The response rate was 69% (n=136/198). Estimated Percutaneous Endoscopic Gastrostomy (PEG) placements in the UK are currently 6500 vs 17 000 in 2010 (p<0.01). There is a dedicated PEG consultant involved in 59% of the centres versus 30% in 2010 (p<0.001). Multidisciplinary team meeting (MDT) discussion occurs in 66% versus 40% in 2010 (p<0.05). Formal aftercare provision occurs in 83% versus 64% in 2010 (p<0.001). 74/107 respondents (69%) reported feeling pressurised to authorise a gastrostomy. Conclusion: This national survey, validated by the results from NED, demonstrates a reduction of over 60% for PEG insertion rates compared with previous estimates. There has also been an increase in consultant involvement, MDT discussion and aftercare provision. However, two-third of responders described 'pressure' to insert a gastrostomy. Perhaps further efforts are needed to include and educate other specialty teams, patients and next of kin.