RESUMEN
The three-dimensional positions of atoms in protein molecules define their structure and their roles in biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more mechanistic insights into protein function may be inferred. Electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years1,2. However, it has proved difficult to obtain cryo-EM reconstructions with sufficient resolution to visualize individual atoms in proteins. Here we use a new electron source, energy filter and camera to obtain a 1.7 Å resolution cryo-EM reconstruction for a human membrane protein, the ß3 GABAA receptor homopentamer3. Such maps allow a detailed understanding of small-molecule coordination, visualization of solvent molecules and alternative conformations for multiple amino acids, and unambiguous building of ordered acidic side chains and glycans. Applied to mouse apoferritin, our strategy led to a 1.22 Å resolution reconstruction that offers a genuine atomic-resolution view of a protein molecule using single-particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualized in difference maps, allowing a direct analysis of hydrogen-bonding networks. Our technological advances, combined with further approaches to accelerate data acquisition and improve sample quality, provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery.
Asunto(s)
Apoferritinas/química , Apoferritinas/ultraestructura , Microscopía por Crioelectrón/instrumentación , Microscopía por Crioelectrón/métodos , Receptores de GABA-A/química , Receptores de GABA-A/ultraestructura , Imagen Individual de Molécula/métodos , Animales , Microscopía por Crioelectrón/normas , Descubrimiento de Drogas , Humanos , Ratones , Modelos Moleculares , Polisacáridos/química , Polisacáridos/ultraestructura , Imagen Individual de Molécula/normasRESUMEN
Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs), are two important mechanisms that regulate the time course of glutamatergic neurotransmission. Prior work has shown that alternative splicing of the flip/flop cassette profoundly regulates TARP γ2 modulation, where flip receptor gating exhibits robust sensitivity to TARPs while flop isoforms are relatively insensitive to TARP modulation. Whether this splice variant-specific regulation extends to other auxiliary subunit families, such as cornichons (CNIHs), GSG1L, or CKAMPs, remains unknown. Here, we demonstrate that CNIH-3 modulation is unaffected by AMPAR alternative splicing due to inherent differences in how CNIH-3 and TARP γ2 modify channel gating. CNIH-3 slows receptor deactivation from the outset of current decay, consistent with structural evidence showing its point of contact at the level of the pore. In contrast, TARP γ2 acts via the KGK site of the ligand-binding domain (LBD) to slow the onset of desensitization. Although GSG1L and CKAMP44 primarily slow recovery from desensitization, their effects on channel gating are unaffected by alternative splicing, further underlining that structural events leading to the onset and recovery from desensitization are separable. Together, this work establishes that alternative splicing and TARP auxiliary subunits form a unique partnership that governs fast glutamatergic signaling at central synapses. Since proteomic studies suggest that all native AMPARs co-assemble with at least two TARPs, allosteric coupling between the flip/flop cassette and TARPs may represent a common design element in all AMPAR complexes of the mammalian brain.SIGNIFICANCE STATEMENT All fast excitatory neurotransmission in the mammalian brain is mediated by AMPA-type glutamate receptors (AMPARs). The time course of AMPAR gating can be regulated by two distinct mechanisms: alternative splicing of the flip/flop cassette and association with auxiliary subunits. Although these regulatory mechanisms have been well studied individually, it is not clear whether alternative splicing impacts auxiliary protein modulation of AMPARs. Here, we compare the four main families of AMPAR auxiliary subunits, transmembrane AMPAR regulatory proteins (TARPs; γ2), cornichons (CNIH-3), GSG1L and CKAMPs (CKAMP44), and find a privileged relationship between TARPs and the flip/flop cassette that is not shared by others. The flop cassette acts as a master switch to override TARP action, and this coupling represents a way to fine-tune AMPAR signaling.
Asunto(s)
Empalme Alternativo , Receptores AMPA , Animales , Receptores AMPA/metabolismo , Empalme Alternativo/genética , Proteómica , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Ácido Glutámico/metabolismo , MamíferosRESUMEN
BACKGROUND: Patients with cancer often endure substantial symptoms and treatment toxicities leading to high healthcare utilization, including hospitalizations and emergency department visits, throughout the continuum of their illness. Innovative oncology care models are needed to improve patient outcomes and reduce their healthcare utilization. Using a novel hospital at home care platform, we developed a Supportive Oncology Care at Home intervention to address the needs of patients with cancer. METHODS: We are conducting three trials to delineate the role of Supportive Oncology Care at Home for patients with cancer. The Supportive Oncology Care at Home intervention includes: (1) a hospital at home care model for symptom assessment and management; (2) remote monitoring of daily patient-reported symptoms, vital signs, and body weight; and (3) structured communication with the oncology team. Our first study is a randomized controlled trial to test the efficacy of Supportive Oncology Care at Home versus standard oncology care for improving healthcare utilization, cancer treatment interruptions, and patient-reported outcomes in patients with cancer receiving definitive treatment of their cancer. Participants include adult patients with gastrointestinal and head and neck cancer, as well as lymphoma, receiving definitive treatment (e.g., treatment with curative intent). The second study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention for hospitalized patients with advanced cancer. Eligible participants include adult patients with incurable cancer who are admitted with an unplanned hospitalization. The third study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention to enhance the end-of-life care for patients with advanced hematologic malignancies. Eligible participants include adult patients with relapsed or refractory hematologic malignancy receiving palliative therapy or supportive care alone. DISCUSSION: These studies are approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board and are being conducted in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. This work has the potential to transform the paradigm of care for patients with cancer by providing them with the necessary support at home to improve their health outcomes and care delivery. TRIAL REGISTRATIONS: NCT04544046, NCT04637035, NCT04690205.
Asunto(s)
Neoplasias de Cabeza y Cuello , Cuidado Terminal , Adulto , Humanos , Cuidados Paliativos/métodos , Medición de Resultados Informados por el Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Evaluación de Síntomas , Cuidado Terminal/métodosRESUMEN
Objective: Measurement feedback systems provide clinicians with regular snapshots of a client's mental health status, which can be used in treatment planning and client feedback. There are numerous barriers to clinicians using outcome measures routinely. This study aimed to investigate factors affecting the use of a measurement feedback system across youth mental health settings. Methods: The participants were 210 clinicians from headspace youth mental health services across Australia. They were surveyed on predictors and use of MyLifeTracker, a routine outcome measure. This was explored through three processes: looking at MyLifeTracker before session, using MyLifeTracker in treatment planning, and providing feedback of MyLifeTracker scores to clients. Results: Clinicians were more likely to look at MyLifeTracker before session, less likely to use it in treatment planning, and least likely to provide MyLifeTracker scores to clients. Each measurement feedback system process had a distinct group of predictors. Perceptions of MyLifeTracker's practicality was the only significant predictor of all three processes. Conclusion: Practically, organisations and supervisors can increase the use of measurement feedback systems through targeted supports.
Asunto(s)
Trastornos Mentales , Servicios de Salud Mental , Adolescente , Retroalimentación , Humanos , Salud Mental , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Despite the 6000 patients treated with extracorporeal membrane oxygenation (ECMO) annually, there is a paucity of data regarding the nutritional management of these patients. MATERIALS AND METHODS: We performed a prospective, observational study of nutrition in postcardiotomy shock patients at our institution. Over a 3.5-year study period, we identified 50 ECMO patients and 225 non-ECMO patients. We identified type, amount, duration, and disruption of nutritional delivery by cohort. The primary outcome was percent of caloric goal met, and secondary outcome was gastrointestinal complications. RESULTS: ECMO patients met less of their caloric (29% versus 40%, P = 0.017) and protein goals (34% versus 55%, P < 0.001) compared with non-ECMO patients. Tube feeds were administered more slowly (26 versus 37 mL/h, P < 0.001) and held for longer (8.3 versus 4.5 h/d, P < 0.001) in ECMO patients because of procedures (60%) and high-dose pressors (20% versus 7%, P < 0.001). Multivariate analysis demonstrated that ECMO decreased caloric intake by 14%, with no detected increased risk of gastrointestinal complications. CONCLUSIONS: -ECMO patients received significantly less nutrition support compared with a non-ECMO population. Tube feed hold deficits could potentially be avoided by utilizing postpyloric tubes to feed through procedures, by eliminating holds for vasopressors/inotropes in hemodynamically stable patients, or by establishing volume-based feeding protocols. Further clinical studies are needed to establish efficacy of these interventions and to understand the impact of nutrition on outcomes in ECMO patients.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Apoyo Nutricional/estadística & datos numéricos , Choque Quirúrgico/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Quirúrgico/etiologíaRESUMEN
Background: Causal beliefs are thought to influence consumers' perceptions of their mental illness and self-stigma, and may impact treatment and recovery. Understanding consumers' perspective on causes being addressed in treatment is vital to help guide future research and improve services. Aim: This study aimed to explore consumers' views on causes of mental illness being addressed in treatment, along with their subjective experiences of how causes were focused on in their treatment. Methods: Using a qualitative approach, semi-structured interviews were conducted with 23 consumers who self-identified as having a mental illness. A thematic analytic framework was used to identify and analyse themes that emerged within the data. Results: Consumers believed that causes were important and should be addressed in treatment, and identified several associated benefits including increased insight/personal understanding of their illness, symptom management and relapse prevention and reduced self-blame. Negative consequences and considerations were also identified. Conclusion: Causes help consumers make sense of their illness, and consumers would like causes to be addressed in treatment. More research is needed on how mental health professionals can address causes effectively as consumers are currently dissatisfied with how causes were discussed in their treatment.
Asunto(s)
Trastornos Mentales/psicología , Trastornos Mentales/terapia , Adulto , Comportamiento del Consumidor , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estigma Social , Adulto JovenRESUMEN
Kainate receptors require the presence of external ions for gating. Most work thus far has been performed on homomeric GluK2 but, in vivo, kainate receptors are likely heterotetramers. Agonists bind to the ligand-binding domain (LBD) which is arranged as a dimer of dimers as exemplified in homomeric structures, but no high-resolution structure currently exists of heteromeric kainate receptors. In a full-length heterotetramer, the LBDs could potentially be arranged either as a GluK2 homomer alongside a GluK5 homomer or as two GluK2/K5 heterodimers. We have constructed models of the LBD dimers based on the GluK2 LBD crystal structures and investigated their stability with molecular dynamics simulations. We have then used the models to make predictions about the functional behavior of the full-length GluK2/K5 receptor, which we confirmed via electrophysiological recordings. A key prediction and observation is that lithium ions bind to the dimer interface of GluK2/K5 heteromers and slow their desensitization.
Asunto(s)
Modelos Moleculares , Multimerización de Proteína , Receptores de Ácido Kaínico/química , Receptores de Ácido Kaínico/metabolismo , Glutamatos/metabolismo , Ligandos , Litio/farmacología , Dominios Proteicos , Multimerización de Proteína/efectos de los fármacos , Estructura Cuaternaria de ProteínaRESUMEN
OBJECTIVES: This paper examined the psychological factors that influence the well-being of health professionals who work with people with dementia and the types of care (person-centred or task-oriented) provided to these patients. METHODS: The literature was reviewed to identify the factors influencing the well-being of, and types of care provided by, health professionals working with people experiencing dementia. RESULTS: Based on our review of the literature, we propose that approaches to care and the well-being of health professionals working with dementia patients are influenced by the characterisation of dementia as a terminal illness that typically occurs in older people. Drawing upon terror management theory, we argue that exposure to dementia patients is likely to promote awareness of one's own mortality and death-related anxiety. A theoretical model is presented which posits that health professionals working in dementia care draw on experiential avoidance to manage this anxiety. Both death anxiety, and coping strategies, such as experiential avoidance, used to manage this anxiety may influence health professionals' approaches to care of, and attitudes towards, dementia patients. We also suggest a bi-directional relationship between health professionals' approaches to care and well-being. CONCLUSION: Recommendations are made regarding future directions for research and implications for training of health professionals providing direct service or consultation in dementia care.
Asunto(s)
Adaptación Psicológica , Actitud del Personal de Salud , Actitud Frente a la Muerte , Demencia/terapia , Personal de Salud/psicología , Ageísmo/psicología , Ansiedad/psicología , Humanos , Modelos Psicológicos , Atención Dirigida al PacienteRESUMEN
Activity-dependent strengthening of central synapses is a key factor driving neuronal circuit behavior in the vertebrate CNS. At fast inhibitory synapses, strengthening is thought to occur by increasing the number of GABAA receptors (GABARs) of the same subunit composition to preexisting synapses. Here, we show that strengthening of mouse cerebellar granule cell GABAergic synapses occurs by a different mechanism. Specifically, we show that the neuropeptide hormone, insulin, strengthens inhibitory synapses by recruiting α6-containing GABARs rather than accumulating more α1-containing receptors that are resident to the synapse. Because α6-receptors are targeted to functionally distinct postsynaptic sites from α1-receptors, we conclude that only a subset of all inhibitory synapses are strengthened. Together with our recent findings on stellate cells, we propose a general mechanism by which mature inhibitory synapses are strengthened. In this scenario, α1-GABARs resident to inhibitory synapses form the hardwiring of neuronal circuits with receptors of a different composition fulfilling a fundamental, but unappreciated, role in synapse strengthening.
Asunto(s)
Cerebelo/citología , Hipoglucemiantes/farmacología , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Insulina/farmacología , Neuronas/efectos de los fármacos , Receptores de GABA-A/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Animales Recién Nacidos , Antagonistas de Aminoácidos Excitadores/farmacología , Furosemida/farmacología , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de GABA-A/genética , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Sinapsis/efectos de los fármacos , Sinapsis/genética , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/genética , Factores de Tiempo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
KEY POINTS: Kainate receptor heteromerization and auxiliary subunits, Neto1 and Neto2, attenuate polyamine ion-channel block by facilitating blocker permeation. Relief of polyamine block in GluK2/GluK5 heteromers results from a key proline residue that produces architectural changes in the channel pore α-helical region. Auxiliary subunits exert an additive effect to heteromerization, and thus relief of polyamine block is due to a different mechanism. Our findings have broad implications for work on polyamine block of other cation-selective ion channels. ABSTRACT: Channel block and permeation by cytoplasmic polyamines is a common feature of many cation-selective ion channels. Although the channel block mechanism has been studied extensively, polyamine permeation has been considered less significant as it occurs at extreme positive membrane potentials. Here, we show that kainate receptor (KAR) heteromerization and association with auxiliary proteins, Neto1 and Neto2, attenuate polyamine block by enhancing blocker permeation. Consequently, polyamine permeation and unblock occur at more negative and physiologically relevant membrane potentials. In GluK2/GluK5 heteromers, enhanced permeation is due to a single proline residue in GluK5 that alters the dynamics of the α-helical region of the selectivity filter. The effect of auxiliary proteins is additive, and therefore the structural basis of polyamine permeation and unblock is through a different mechanism. As native receptors are thought to assemble as heteromers in complex with auxiliary proteins, our data identify an unappreciated impact of polyamine permeation in shaping the signalling properties of neuronal KARs and point to a structural mechanism that may be shared amongst other cation-selective ion channels.
Asunto(s)
Activación del Canal Iónico , Lipoproteínas LDL/metabolismo , Proteínas de la Membrana/metabolismo , Poliaminas/metabolismo , Receptores de Ácido Kaínico/metabolismo , Animales , Células HEK293 , Humanos , Proteínas Relacionadas con Receptor de LDL , Potenciales de la Membrana , Ratones , Dominios Proteicos , Ratas , Receptores de N-Metil-D-Aspartato , Receptor de Ácido Kaínico GluK2RESUMEN
BACKGROUND: Few studies have examined the relationship of social anxiety with drinking game participation. Drinking games represent a popular form of drinking in university settings. Due to their structure, games may appeal to socially anxious drinkers, particularly among those seeking to fit in or cope with the social setting. OBJECTIVES: To examine the relationship of social anxiety with frequency of drinking game participation among a university undergraduate sample and to investigate if drinking motives moderate this association. METHOD: A total of 227 undergraduate students aged 18-24 years (73% female) who had consumed alcohol in the prior year were included in the current investigation. Hierarchical regression examined the influences of social anxiety and drinking motives on frequency of drinking game participation, as well the interactions of social anxiety with drinking for coping motives and conformity motives. RESULTS: Social anxiety failed to emerge as a significant predictor of frequency of drinking game participation. However, drinking to cope moderated the relationship of social anxiety with frequency of drinking game participation. Socially anxious students who drank to cope were more likely to participate in drinking games on occasions when they consumed alcohol than those who did not endorse this drinking motive. CONCLUSION: Results demonstrated the influence of drinking to cope in the relationship of social anxiety with frequency of drinking game participation. Future work should examine the relationship with other indicators of drinking game activity. Intervention efforts addressing social anxiety and drinking should consider motives for drinking, as well as drinking patterns.
Asunto(s)
Adaptación Psicológica , Consumo de Bebidas Alcohólicas/epidemiología , Fobia Social/psicología , Estudiantes , Adolescente , Consumo de Bebidas Alcohólicas/psicología , Consumo de Alcohol en la Universidad/psicología , Femenino , Humanos , Masculino , Motivación , Juego e Implementos de Juego/psicología , Análisis de Regresión , Conformidad Social , Universidades , Adulto JovenRESUMEN
Hydrogen peroxide (H2O2), a key reactive oxygen species, is produced at low levels during normal cellular metabolism and at higher concentrations under pathological conditions such as ischemia-reperfusion injury. The mechanisms by which H2O2 contributes to physiological and pathological processes in the brain remain poorly understood. Inhibitory GABA type A (GABAA) receptors critically regulate brain function by generating tonic and synaptic currents; however, it remains unknown whether H2O2 directly modulates GABAA receptor function. Here, we performed patch-clamp recordings, together with pharmacological and genetic approaches, to investigate the effects of H2O2 on GABAA receptor-mediated tonic and synaptic currents recorded in cultured mouse hippocampal neurons and CA1 pyramidal neurons in hippocampal slices. We found that H2O2 caused a dramatic increase in tonic current, whereas synaptic currents were unaffected. This increase in tonic current resulted from an extracellular oxidative reaction, which increased the potency of GABA, but only when GABAA receptors were activated by low concentrations of GABA. Oxygen-glucose deprivation, which produces high endogenous levels of H2O2, similarly increased the tonic current. These results suggest that GABAA receptor-mediated tonic current, which is potentiated by H2O2, might contribute to H2O2-induced brain dysfunction.
Asunto(s)
Hipocampo/citología , Peróxido de Hidrógeno/farmacología , Neuronas/efectos de los fármacos , Oxidantes/farmacología , Receptores de GABA-A/metabolismo , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos , Glucosa/deficiencia , Hipoxia/patología , Hipoxia/fisiopatología , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Potenciales Postsinápticos Inhibidores/genética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Especies Reactivas de Oxígeno/metabolismo , Receptores de GABA-A/genéticaRESUMEN
Intuitive eating is an adaptive and flexible form of eating. Men report higher rates of intuitive eating than women. Objectification processes are proposed to underlie this (binary) gender difference due to the intense body-related pressures that disrupt body image in women. The current study is the first known to test whether body image indirectly explains lower levels of intuitive eating in women relative to men. A cross-sectional sample of 498 adults aged 18-74 years recruited through Prolific completed an online survey assessing intuitive eating and negative and positive body image indicators. Women reported poorer body image and lower levels of intuitive eating compared to men. Significant indirect effects suggested body image explained gender differences in intuitive eating, controlling for age and body mass index. In women relative to men, greater body surveillance and lower aesthetic satisfaction explained lower total intuitive eating and reliance on hunger and satiety, greater aesthetic investment explained lower total intuitive eating and eating for physical reasons, and lower functionality investment explained lower body-food choice congruence. More research is needed, but findings suggest programs may benefit from decreasing critical views of appearance and strengthening functionality investment in women to reduce gender differences in intuitive eating.
Asunto(s)
Conducta Alimentaria , Trastornos de Alimentación y de la Ingestión de Alimentos , Adulto , Masculino , Humanos , Femenino , Imagen Corporal/psicología , Estudios Transversales , Índice de Masa Corporal , Saciedad , Encuestas y Cuestionarios , Ingestión de AlimentosRESUMEN
OBJECTIVE: Young drivers are overrepresented in road traffic crashes and fatalities. Distracted driving, including use of a smartphone while driving (SWD), is a major risk factor for crashes for this age group. We evaluated a web-based tool (Drive in the Moment or DITM) designed to reduce SWD among young drivers. METHODS: A pretest-posttest experimental design with a follow-up was used to assess the efficacy of the DITM intervention on SWD intentions and behaviors, and perceived risk (of having a crash and of being apprehended by the police) associated with SWD. One hundred and eighty young drivers (aged 17-25 years old) were randomly assigned to either the DITM intervention or a control group where participants completed an unrelated activity. Self-reported measures of SWD and perceptions of risk were obtained pre-intervention, immediately post-intervention and at a follow-up 25 days after the intervention. RESULTS: Participants who engaged with the DITM showed a significant reduction in the number of times they used their SWD at follow-up compared to their pre-intervention scores. Future intentions to SWD were also reduced from pre-intervention to post-intervention and follow-up. There was also an increase in the perceived risk of SWD following the intervention. CONCLUSIONS: Our evaluation of DITM suggests that the intervention had an impact on reducing SWD among young drivers. Further research is needed to establish which particular elements of the DITM are associated with reductions in SWD and whether similar findings would be identified in other age groups.
Asunto(s)
Conducción de Automóvil , Conducción Distraída , Humanos , Adolescente , Adulto Joven , Adulto , Accidentes de Tránsito/prevención & control , Teléfono Inteligente , InternetRESUMEN
INTRODUCTION: Young drivers continue to be overrepresented in road crash statistics and smartphone use has been identified as a dangerous form of driver distraction. Previous research has identified factors encouraging drivers to use their mobile phone, with few examining what deters drivers. This study examines the influence of legal and non-legal deterrents on smartphone use while driving (SWD) in a young adult sample. METHOD: An online survey was administered to a sample of 524 Australian drivers aged 17-25â¯years. Measures included demographic variables, legal deterrents (certainty, severity, and swiftness), and non-legal deterrents: social loss (peers and parents), internal loss (anticipated regret) and physical loss (injury to self/others). Self-reported SWD was the outcome variable, measured separately for initiating SWD and responding SWD behaviors. RESULTS: Responding behaviors were reported more frequently than initiating, and social, internal, and physical loss were perceived as higher for initiating versus responding behaviors. Anticipated action regret and physical loss were significant negative predictors of SWD across both modalities of communication. Anticipated inaction regret was also a significant positive predictor of initiating behaviors. Both legal deterrents and social loss were non-significant predictors for both modalities of SWD. CONCLUSIONS: The results reinforce previous evidence showing that legal deterrence variables are not consistently effective at reducing offending behaviors. Future research should continue to explore the effect of non-legal deterrents across different modalities of SWD. PRACTICAL APPLICATIONS: Road safety interventions aimed at young drivers should evaluate the impact of highlighting anticipated regret and potential injury to self and others associated with risky driving behaviors, such as SWD.
Asunto(s)
Conducción de Automóvil , Conducción Distraída , Humanos , Australia , PadresRESUMEN
Enteral nutrition (EN) is a vital component of nutrition around the world. EN allows for delivery of nutrients to those who cannot maintain adequate nutrition by oral intake alone. Common questions regarding EN are when to initiate and in what scenarios it is safe. The answers to these questions are often complex and require an evidence-based approach. The Board of Directors of the American Society for Parenteral and Enteral Nutrition (ASPEN) established an Enteral Nutrition Committtee to address the important questions surrounding the indications for EN. Consensus recommendations were established based on eight extremely clinically relevant questions regarding EN indications as deemed by the Enteral Nutrition Committee. These consensus recommendations may act as a guide for clinicians and stakeholders on difficult questions pertaining to indications for EN. This paper was approved by the ASPEN Board of Directors.
Asunto(s)
Nutrición Enteral , Nutrición Parenteral , ConsensoRESUMEN
PURPOSE: We sought to determine the feasibility of delivering a Supportive Oncology Care at Home intervention among patients with pancreatic cancer. METHODS: We prospectively enrolled patients with pancreatic cancer from a parent trial of neoadjuvant fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX). The intervention entailed (1) remote monitoring of patient-reported symptoms, vital signs, and body weight; (2) a hospital-at-home care model; and (3) structured communication with the oncology team. We defined the intervention as feasible if ≥ 60% of patients enrolled in the study and ≥ 60% completed the daily assessments within the first 2-weeks of enrollment. We determined rates of treatment delays, urgent clinic visits, emergency department visits, and hospitalizations among those who did (n = 20) and did not (n = 24) receive Supportive Oncology Care at Home from the parent trial. RESULTS: From January 2019 to September 2020, we enrolled 80.8% (21/26) of potentially eligible patients. One patient became ineligible following consent because of moving out of state, resulting in 20 participants (median age = 67 years). In the first 2 weeks of enrollment, 65.0% of participants completed all daily assessments. Overall, patients reported 96.1% of daily symptoms, 96.1% of daily vital signs, and 92.5% of weekly body weights. Patients receiving the intervention had lower rates of treatment delays (55.0% v 75.0%), urgent clinic visits (10.0% v 25.0%), and emergency department visits/hospitalizations (45.0% v 62.5%) compared with those not receiving the intervention from the same parent trial. CONCLUSION: Findings demonstrate the feasibility and acceptability of a Supportive Oncology Care at Home intervention. Future work will investigate the efficacy of this intervention for decreasing health care use and improving patient outcomes.
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Neoplasias Pancreáticas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fluorouracilo/efectos adversos , Humanos , Irinotecán/efectos adversos , Leucovorina/efectos adversos , Oxaliplatino/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/terapia , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To explore health professionals' (clinicians) approach to the provision of care in a dementia setting. METHODS: Participants were clinicians from two older persons' mental health services (community and inpatient). Participants completed an interview about strategies to engage with, and barriers to providing person-centred care to consumers with a co-morbid diagnosis of dementia. Thematic analysis was used to analyse the data. RESULTS: Three main themes were developed through analysis of the interview data: (1) overall approach to care (synthesis of care and cure principles), (2) the challenges in the provision of care, and (3) coping strategies to manage care demands. CONCLUSION: Developing a relationship with a patient and attending to their medical needs were seen as optimal care, relevant to both person-centred and task-oriented approaches to dementia care. Clinicians also highlighted the importance of their own personal resources and attitudes in shaping the type of care provided.
Asunto(s)
Demencia , Salud Mental , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Demencia/diagnóstico , Demencia/terapia , Humanos , Morbilidad , Atención Dirigida al PacienteRESUMEN
Establishing a relationship is considered the foundation of providing person-centred care (PCC) when working with a person who has a diagnosis of dementia. Currently, there is a lack of consensus about the how to develop this relationship. This aim of this study was to explore the key skills adopted by clinicians to establish an effective care relationship, referred to as therapeutic alliance, specific to working with patients who have dementia. Participants were clinicians (nursing and allied health professionals) from two older person's mental health service teams (inpatient and community) who routinely provided clinical care to patients with a diagnosis of dementia. Participants self-selected from a purposive sample to complete a semi-structured interview about their provision of care to, and strategies used to engage with, people with a diagnosis of dementia. Exploratory qualitative thematic analysis was conducted using mixed inductive and deductive procedures. Five themes were identified as the interpersonal skills used to develop relationships with patients including the following: empathy, unconditional positive regard, congruence, psychological flexibility, and communication. Findings from this study provide direction for training of clinicians employed in a dementia setting and can also be generalized to other non-specific clinical settings where clinicians may incidentally provide treatment to patients with a diagnosis of dementia.
Asunto(s)
Demencia , Alianza Terapéutica , Anciano , Comunicación , Demencia/diagnóstico , Demencia/terapia , Emociones , Humanos , AutocuidadoRESUMEN
Mobile phone use while driving (MWD) is a threat to road safety, particularly for younger drivers. Research suggests impulsivity may be a psychological risk factor for MWD, however, the literature is limited. The current study examined the unique contributions of impulsivity facets on different social interactive MWD behaviours, and whether these relationships were influenced by mobile phone involvement. Eight hundred and fifty-three young drivers aged 17-25 years (Mage = 19.89; 74 % female) completed an online questionnaire which included measures of the five-facet model of impulsivity, mobile phone involvement, and MWD (initiating, monitoring/reading, and responding to social communications). Of impulsivity facets, lower premeditation and higher positive urgency significantly predicted each MWD behaviour, while higher sensation seeking significantly predicted responding only, providing some support for differential relationships of impulsivity facets with MWD. Mobile phone involvement was a more robust predictor of MWD. Moreover, there were significant indirect effects of positive and negative urgency via mobile phone involvement for all three MWD behaviours. Findings highlight the importance of mobile phone involvement for explaining MWD which should be addressed in future studies.