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Our brain adeptly navigates goals across time frames, distinguishing between urgent needs and those of the past or future. The hippocampus is a region known for supporting mental time travel and organizing information along its longitudinal axis, transitioning from detailed posterior representations to generalized anterior ones. This study investigates the role of the hippocampus in distinguishing goals over time: whether the hippocampus encodes time regardless of detail or abstraction, and whether the hippocampus preferentially activates its anterior region for temporally distant goals (past and future) and its posterior region for immediate goals. We use a space-themed experiment with 7T functional MRI on 31 participants to examine how the hippocampus encodes the temporal distance of goals. During a simulated Mars mission, we find that the hippocampus tracks goals solely by temporal proximity. We show that past and future goals activate the left anterior hippocampus, while current goals engage the left posterior hippocampus. This suggests that the hippocampus maps goals using timestamps, extending its long axis system to include temporal goal organization.
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Mapeamento Encefálico , Objetivos , Hipocampo , Imageamento por Ressonância Magnética , Humanos , Hipocampo/fisiologia , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto , Adulto Jovem , Mapeamento Encefálico/métodosRESUMO
INTRODUCTION: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (<70 years) adults in our population. MATERIALS AND METHODS: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (<70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses. RESULTS: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p < 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p < 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p < 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p < 0.001). Whilst older adults had poorer median OS than those aged <70 years (12.0 vs 34.4 months, p < 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not. DISCUSSION: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.
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Neoplasias Colorretais , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Escócia/epidemiologia , Adulto , Modelos de Riscos Proporcionais , Fatores Etários , Adulto Jovem , Estimativa de Kaplan-Meier , Emergências , Serviço Hospitalar de Emergência/estatística & dados numéricosRESUMO
Aims: Ankle fractures are common injuries and the third most common fragility fracture. In all, 40% of ankle fractures in the frail are open and represent a complex clinical scenario, with morbidity and mortality rates similar to hip fracture patients. They have a higher risk of complications, such as wound infections, malunion, hospital-acquired infections, pressure sores, veno-thromboembolic events, and significant sarcopaenia from prolonged bed rest. Methods: A modified Delphi method was used and a group of experts with a vested interest in best practice were invited from the British Foot and Ankle Society (BOFAS), British Orthopaedic Association (BOA), Orthopaedic Trauma Society (OTS), British Association of Plastic & Reconstructive Surgeons (BAPRAS), British Geriatric Society (BGS), and the British Limb Reconstruction Society (BLRS). Results: In the first stage, there were 36 respondents to the survey, with over 70% stating their unit treats more than 20 such cases per year. There was a 50:50 split regarding if the timing of surgery should be within 36 hours, as per the hip fracture guidelines, or 72 hours, as per the open fracture guidelines. Overall, 75% would attempt primary wound closure and 25% would utilize a local flap. There was no orthopaedic agreement on fixation, and 75% would permit weightbearing immediately. In the second stage, performed at the BLRS meeting, experts discussed the survey results and agreed upon a consensus for the management of open elderly ankle fractures. Conclusion: A mutually agreed consensus from the expert panel was reached to enable the best practice for the management of patients with frailty with an open ankle fracture: 1) all units managing lower limb fragility fractures should do so through a cohorted multidisciplinary pathway. This pathway should follow the standards laid down in the "care of the older or frail orthopaedic trauma patient" British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guideline. These patients have low bone density, and we should recommend full falls and bone health assessment; 2) all open lower limb fragility fractures should be treated in a single stage within 24 hours of injury if possible; 3) all patients with fragility fractures of the lower limb should be considered for mobilisation on the day following surgery; 4) all patients with lower limb open fragility fractures should be considered for tissue sparing, with judicious debridement as a default; 5) all patients with open lower limb fragility fractures should be managed by a consultant plastic surgeon with primary closure wherever possible; and 6) the method of fixation must allow for immediate unrestricted weightbearing.
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BACKGROUND: Frailty is known to be a predictor of poor recovery following trauma and there is evidence that providing early frailty specific care can improve functional and health outcomes. Accurate assessment of frailty is key to its early identification and subsequent provision of specialist care. The aim of this study was to determine the feasibility and acceptability of different frailty screening tools to nurses administering them in the ED in patients admitted following traumatic injury. METHODS: Patients aged 65 and over attending the Emergency Department of five major trauma centres following injury participated in the study between June 2019 and March 2020. Patients were assessed using the clinical frailty scale (CFS), Program of Research to Integrate Services for the Maintenance of Autonomy 7 (PRIMSA7), and the Trauma Specific Frailty Index (TSFI). Nurses were asked to rank ease of use and to state their preference for each of the tools from best to worst. If the tool was not able to be completed fully then free text responses were enabled to identify reasons. Accuracy of the tool in identifying if the patient was frail or not was determined by comparison with frailty determined by a geriatrician. RESULTS: Data were analysed from 372 patients. Completion rates for each of the tools varied, with highest degree of compliance using the CFS (98.9%). TSFI was least likely to be completed with "lack of available information to complete questions" as the most cited reason. Nurses showed a clear preference for the CFS with 57.3% ranking this as first choice (PRISMA-7 32.16%; TSFI 10.54%). Both PRISMA-7 and CFS were both rated highly as 'extremely easy to complete' (PRISMA-7 58.5%, CFS 59.61%). CONCLUSION: Our results suggest that nurses from five centres preferred to use the CFS to assess frailty in ED major trauma patients.
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Fragilidade , Enfermeiras e Enfermeiros , Idoso , Humanos , Fragilidade/diagnóstico , Idoso Fragilizado , Estudos Transversais , Estudos Prospectivos , Avaliação Geriátrica/métodosRESUMO
BACKGROUND: Pre-injury frailty is associated with adverse in-hospital outcomes in older trauma patients, but the association with longer term survival and recovery is unclear. We aimed to investigate post discharge survival and health-related quality of life (HRQoL) in older frail patients at six months after Major Trauma Centre (MTC) admission. METHODS: This was a multi-centre study of patients aged ≥ 65 years admitted to five MTCs. Data were collected via questionnaire at hospital discharge and six months later. The primary outcome was patient-reported HRQoL at follow up using Euroqol EQ5D-5 L visual analogue scale (VAS). Secondary outcomes included health status according to EQ5D dimensions and care requirements at follow up. Multivariable linear regression analysis was conducted to evaluate the association between predictor variables and EQ-5D-5 L VAS at follow up. RESULTS: Fifty-four patients died in the follow up period, of which two-third (64%) had been categorised as frail pre-injury, compared to 21 (16%) of the 133 survivors. There was no difference in self-reported HRQoL between frail and not-frail patients at discharge (Mean EQ-VAS: Frail 55.8 vs. Not-frail 64.1, p = 0.137) however at follow-up HRQoL had improved for the not-frail group but deteriorated for frail patients (Mean EQ-VAS: Frail: 50.0 vs. Not-frail: 65.8, p = 0.009). There was a two-fold increase in poor quality of life at six months (VAS ≤ 50) for frail patients (Frail: 65% vs. Not-frail: 30% p < 0.009). Frailty (ß-13.741 [95% CI -25.377, 2.105], p = 0.02), increased age (ß -1.064 [95% CI [-1.705, -0.423] p = 0.00) and non-home discharge (ß -12.017 [95% CI [118.403, 207.203], p = 0.04) were associated with worse HRQoL at follow up. Requirements for professional carers increased five-fold in frail patients at follow-up (Frail: 25% vs. Not-frail: 4%, p = 0.01). CONCLUSIONS: Frailty is associated with increased mortality post trauma discharge and frail older trauma survivors had worse HRQoL and increased care needs at six months post-discharge. Pre-injury frailty is a predictor of poor longer-term HRQoL after trauma and recognition should enable early specialist pathways and discharge planning.
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Fragilidade , Idoso , Humanos , Fragilidade/epidemiologia , Seguimentos , Idoso Fragilizado , Assistência ao Convalescente , Qualidade de Vida , Centros de Traumatologia , Alta do Paciente , Reino Unido/epidemiologiaRESUMO
PURPOSE: This systematic review aimed to understand older people's perspectives of associated fear-avoidant beliefs following upper limb fracture. METHODS: Published and unpublished literature databases were systematically searched from inception to 1st April 2023. Qualitative studies reporting the perspectives of fear-avoidant beliefs or behaviours in people who had sustained an upper limb fracture were eligible. Data extracted included characteristics of people interviewed, experiences and perceptions of fear, fear of falling, and fear-avoidant beliefs and behaviours. Data were synthesised using a meta-ethnography approach and the GRADE-CERQUAL tool. RESULTS: Eight studies were eligible (n = 150 participants; 109 distal radial/41 humeral fracture). Three overarching themes were identified: (1) type of fear-avoidant experiences, (2) drivers of fear-avoidant beliefs and behaviours, and (3) consequences of fear-avoidant beliefs and behaviours. The themes generated were based on moderate confidence evidence. In summary, whilst some patients initially consider upper limb fractures to be relatively minor injuries, over time, the realisation occurs that they have wide-ranging consequences with longer-term perspectives on recovery. This often occurs following an initial period of reduced fear. Providing education and support immediately post-fracture to prevent or challenge initial health beliefs around fear of falls and fear of movement is imperative to recovery. CONCLUSIONS: Fear-avoidant beliefs can impact heavily on certain older people's recovery, as well as their longer-term health and wellbeing. Consideration of fear avoidance and taking steps to mitigate against this in the acute upper limb trauma setting will better serve these patients in their ongoing recovery from injury.
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Acidentes por Quedas , Medo , Humanos , Medo/psicologia , Idoso , Antropologia Cultural , Fraturas do Úmero/psicologia , Fraturas do Rádio/psicologia , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
In humans, social participation and integration wane with advanced age, a pattern hypothesized to stem from cognitive or physical decrements. Similar age-related decreases in social participation have been observed in several nonhuman primate species. Here, we investigated cross-sectional age-related associations between social interactions, activity patterns, and cognitive function in 25 group-living female vervets (a.k.a. African green monkeys, Chlorocebus sabaeus) aged 8-29 years. Time spent in affiliative behavior decreased with age, and time spent alone correspondingly increased. Furthermore, time spent grooming others decreased with age, but the amount of grooming received did not. The number of social partners to whom individuals directed grooming also decreased with age. Grooming patterns mirrored physical activity levels, which also decreased with age. The relationship between age and grooming time was mediated, in part, by cognitive performance. Specifically, executive function significantly mediated age's effect on time spent in grooming interactions. In contrast, we did not find evidence that physical performance mediated age-related variation in social participation. Taken together, our results suggest that aging female vervets were not socially excluded but decreasingly engaged in social behavior, and that cognitive deficits may underlie this relationship.
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Função Executiva , Comportamento Social , Humanos , Animais , Chlorocebus aethiops , Feminino , Estudos Transversais , Envelhecimento , Integração SocialRESUMO
Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula.
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Posterior fossa ependymomas (PFEs) are designated histologically as low-grade neoplasms. Despite being characterised as benign, cases of metastasis have been reported only a few times with the patients concurrently diagnosed with the primary tumour. Interval drop metastasis or spontaneous second distal tumours are extremely rare and, in most cases, are diagnosed within a few months of primary tumour resection. Here, we report a patient with a grade 2 paediatric PFE exhibiting a 20-year interval to a second sacral ependymoma. The patient was initially diagnosed with a PFE at the age of 10 years and underwent tumour resection and postoperative radiotherapy. In their late 20s, the patient presented with basilar artery occlusion complicated by life-threatening epistaxis. Post-thrombolysis, the patient presented with a large sacral grade 1 myxopapillary ependymoma with cauda equina syndrome-like symptoms. Here, we present a rare case of two ependymomas with a 20-year interval in the same patient with compounding comorbidities.
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Ependimoma , Neoplasias da Medula Espinal , Humanos , Criança , Ependimoma/diagnóstico , Ependimoma/cirurgia , Ependimoma/patologia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Medula Espinal/complicaçõesRESUMO
The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.
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Disfunção Cognitiva , Multiômica , Humanos , Animais , Feminino , Envelhecimento/psicologia , Transdução de Sinais/genética , Córtex Pré-Frontal/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismoRESUMO
Action-outcome associations depend on prefrontal cortex (PFC) projections to the dorsal striatum. To assess how these projections form, we measured PFC axon patterning, synapse formation, and functional maturation in the postnatally developing mouse striatum. Using Hotspot analysis, we show that PFC axons form an adult-like pattern of clustered terminations in the first postnatal week that remains largely stable thereafter. PFC-striatal synaptic strength is adult-like by P21, while excitatory synapse density increases until adulthood. We then tested how the targeted deletion of a candidate adhesion/guidance protein, Cadherin-8 (Cdh8), from corticostriatal neurons regulates pathway development. Mutant mice showed diminished PFC axon targeting and reduced spontaneous glutamatergic synaptic activity in the dorsal striatum. They also exhibited impaired behavioral performance in action-outcome learning. The data show that PFC-striatal axons form striatal territories through an early, directed growth model and they highlight essential contributions of Cdh8 to the anatomical and functional features critical for the formation of action-outcome associations.
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Our brain must manage multiple goals that differ in their temporal proximity. Some goals require immediate attention, while others have already been accomplished, or will be relevant later in time. Here, we examined how the hippocampus represents the temporal distance to different goals using a novel space-themed paradigm during 7T functional MRI (n=31). The hippocampus has an established role in mental time travel and a system in place to stratify information along its longitudinal axis on the basis of representational granularity. Previous work has documented a functional transformation from fine-grained, detail rich representations in the posterior hippocampus to coarse, gist-like representations in the anterior hippocampus. We tested whether the hippocampus uses this long axis system to dissociate goals based upon their temporal distance from the present. We hypothesized that the hippocampus would distinguish goals relevant for ones' current needs from those that are removed in time along the long axis, with temporally removed past and future goals eliciting increasingly anterior activation. We sent participants on a mission to Mars where they had to track goals that differed in when they needed to be accomplished. We observed a long-axis dissociation, where temporally removed past and future goals activated the left anterior hippocampus and current goals activated the left posterior hippocampus. Altogether, this study demonstrates that the timestamp attached to a goal is a key driver in where the goal is represented in the hippocampus. This work extends the scope of the hippocampus' long axis system to the goal-mapping domain.
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Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (3.5-13.6 years) and 71 aged (19.9-32.5 years of age at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching-to-sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all three tasks. Acquisition of delayed response and delayed nonmatching-to-sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching-to-sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe. (181 words).
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Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (aged 3.5-13.6 years) and 71 aged (aged 19.9-32.5 years at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching to sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all 3 tasks. Acquisition of delayed response and delayed nonmatching to sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching to sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for multiple cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe.
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Envelhecimento Cognitivo , Humanos , Animais , Masculino , Feminino , Macaca mulatta , Neuropsicologia , Envelhecimento/fisiologia , Memória de Curto Prazo/fisiologiaRESUMO
Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.
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Glucuronidase , Longevidade , Camundongos , Humanos , Animais , Idoso , Glucuronidase/metabolismo , Envelhecimento , Cognição , Primatas/metabolismoRESUMO
BACKGROUND: Diagnosis of major trauma in the older person is increasingly recognised as clinically challenging with recent reports finding that older patients sustaining major trauma are commonly under-recognised and subsequently are not receiving gold standard major trauma care. This paper is a service evaluation of the processes of major trauma (ISS > 15) care for patients > 65 years presenting to a UK major trauma centre. AIM: To identify modifiable factors within the patient journey that might inform future service improvement initiatives. METHODS: TARN audit data and retrospective notes review of 190 patients > 65 presenting to UHS ED from 1st January 2018 - 31st December 2018 who did not receive a level 1 trauma call on arrival were used to achieve the dataset. Descriptive statistics were combined with multiple logistic regression to look for associations between specific process factors and a missed or delayed diagnosis. RESULTS: The evaluation found that, of the cohort not receiving a level 1 trauma call, 42 (22.1%) patients received a level 2 trauma call; 87 (45.7%) patients were seen initially by a senior clinician, with only 31 (16.3%) patients meeting best practice tariff for consultant within 5 min; 60 (31.5%) patients were seen directly in the resuscitation room; 48 (25.2%) patients received a trauma CT scan with only 27 (14.2%) meeting BPT for CT head within 1 h; 142 (74.7%) patients were admitted to a trauma specialty after discharge from ED. A total of 76 (40%) patients had a missed diagnosis of major trauma with 80 (42%) having a delayed diagnosis. Logistic regression showed a significant association between being seen in a standard initial assessment area (referred to as pitstop in this article) vs the resuscitation room as a first location (p = 0.007) with a delayed diagnosis; and a significant association between plain film imaging vs CT imaging (p = 0.000) and no trauma call vs trauma call (p = 0.009) with a missed diagnosis of major trauma. CONCLUSION: The findings of this service evaluation suggest that service improvement initiatives should be aimed at the early stages of the patient journey to improve missed or delayed diagnoses of major trauma in this patient group.
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Tomografia Computadorizada por Raios X , Centros de Traumatologia , Humanos , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Serviço Hospitalar de EmergênciaRESUMO
Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and ß. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52-90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERß expression. There was no survival impact according to ERß expression level. Female sex and younger age were associated with lower ERß expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age.
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Rational decision making is grounded in learning to associate actions with outcomes, a process that depends on projections from prefrontal cortex to dorsomedial striatum. Symptoms associated with a variety of human pathological conditions ranging from schizophrenia and autism to Huntington's and Parkinson's disease point toward functional deficits in this projection, but its development is not well understood, making it difficult to investigate how perturbations in development of this circuitry could contribute to pathophysiology. We applied a novel strategy based on Hotspot Analysis to assess the developmental progression of anatomical positioning of prefrontal cortex to striatal projections. Corticostriatal axonal territories established at P7 expand in concert with striatal growth but remain largely unchanged in positioning through adulthood, indicating they are generated by directed, targeted growth and not modified extensively by postnatal experience. Consistent with these findings, corticostriatal synaptogenesis increased steadily from P7 to P56, with no evidence for widescale pruning. As corticostriatal synapse density increased over late postnatal ages, the strength of evoked PFC input onto dorsomedial striatal projection neurons also increased, but spontaneous glutamatergic synaptic activity was stable. Based on its pattern of expression, we asked whether the adhesion protein, Cdh8, influenced this progression. In mice lacking Cdh8 in PFC corticostriatal projection neurons, axon terminal fields in dorsal striatum shifted ventrally. Corticostriatal synaptogenesis was unimpeded, but spontaneous EPSC frequency declined and mice failed to learn to associate an action with an outcome. Collectively these findings show that corticostriatal axons grow to their target zone and are restrained from an early age, do not undergo postnatal synapse pruning as the most dominant models predict, and that a relatively modest shift in terminal arbor positioning and synapse function has an outsized, negative impact on corticostriatal-dependent behavior.
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OBJECTIVE: To systematically review research on acute hospital care for frail or older adults experiencing moderate to major trauma. SETTING: Electronic databases (Medline, Embase, ASSIA, CINAHL Plus, SCOPUS, PsycINFO, EconLit, The Cochrane Library) were searched using index and key words, and reference lists and related articles hand-searched. INCLUDED ARTICLES: Peer-reviewed articles of any study design, published in English, 1999-2020 inclusive, referring to models of care for frail and/or older people in the acute hospital phase of care following traumatic injury defined as either moderate or major (mean or median Injury Severity Score ≥9). Excluded articles reported no empirical findings, were abstracts or literature reviews, or referred to frailty screening alone. METHODS: Screening abstracts and full text, and completing data extractions and quality assessments using QualSyst was a blinded parallel process. A narrative synthesis, grouped by intervention type, was undertaken. OUTCOME MEASURES: Any outcomes reported for patients, staff or care system. RESULTS: 17 603 references were identified and 518 read in full; 22 were included-frailty and major trauma (n=0), frailty and moderate trauma (n=1), older people and major trauma (n=8), moderate or major trauma (n=7) 0r moderate trauma (n=6) . Studies were observational, heterogeneous in intervention and with variable methodological quality.Specific attention given to the care of older and/or frail people with moderate to major trauma in the North American context resulted in improvements to in-hospital processes and clinical outcomes, but highlights a relative paucity of evidence, particularly in relation to the first 48 hours post-injury. CONCLUSIONS: This systematic review supports the need for, and further research into an intervention to address the care of frail and/or older patients with major trauma, and for the careful definition of age and frailty in relation to moderate or major trauma. INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS PROSPERO: CRD42016032895.