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An inherent elevation in type 2 immunity is a feature of maternal and offspring immune systems. This has diverse implications for maternal and offspring biology including influencing success of pregnancy, offspring immune development and maternal and offspring ability to control infection and diseases such as allergies. In this review we provide a broad insight into how this immunological feature of pregnancy and early life impacts both maternal and offspring biology. We also suggest how understanding of this axis of immune influence is and may be utilised to improve maternal and offspring health.
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Hipersensibilidade , Feminino , Humanos , GravidezRESUMO
Post-traumatic stress disorder (PTSD) is a debilitating mental health condition characterized by recurrent re-experiencing of traumatic events. Despite increasing evidence suggesting that the cerebellum is involved in PTSD pathophysiology, it remains unclear whether this involvement is related to symptoms directly resulting from previous trauma exposure, such as involuntary re-experiencing of the traumatic events, or reflects a broader cerebellar engagement in negative affective states. In this study, we investigated the specific role of the cerebellum in PTSD by employing a script reactivation paradigm with personalized traumatic and sad autobiographical memories in 28 individuals diagnosed with chronic PTSD. Functional magnetic resonance imaging (fMRI) data were collected while participants listened to their own autobiographical narratives recounted by a third person. Activation in the right cerebellar lobule VI was uniquely associated with traumatic autobiographical recall and was parametrically modulated by the severity of re-experiencing symptoms. In contrast, cerebellar Crus II showed increased activation during both traumatic and sad autobiographical recall, suggesting a broader involvement in processing negative emotions. Our findings highlight the unique contribution of the right cerebellar lobule VI in the processing of traumatic autobiographical memories, potentially through its engagement in low-level representation of sensory and emotional aspects of traumatic events.
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BACKGROUND: Common titration strategies for vagus nerve stimulation (VNS) prioritize monitoring of tolerability during small increases in stimulation intensity over several months. Prioritization of tolerability is partially based on how quickly side effects can be perceived and reported by patients, and the delayed onset of clinical benefits from VNS. However, many practices assess the clinical benefit of VNS at one year after implantation, and excessive caution during the titration phase can significantly delay target dosing or prevent a patient from reaching a therapeutic dose entirely. OBJECTIVE: This study aimed to characterize the relationship between titration speed and the onset of clinical response to VNS. METHODS: To assess differences between more aggressive titration strategies and more conservative ones, we analyzed the relationship between time-to-dose and time-to-response using a weighted Cox regression. The target dose was empirically defined as 1.625 mA output current delivered at 250 microsecond pulse widths at 20 Hz. Patient-level outcomes and dosing data were segregated into fast (<3 months), medium (3-6 months), and slow (>6 months) cohorts based on their titration speed. RESULTS: The statistical model revealed a significant relationship between titration speed and onset of clinical response, defined as a 50% reduction from baseline in seizure frequency. Frequency of adverse events reported between each cohort trended toward higher rates of adverse events in adults who were titrated quickly; however, the pediatric population appeared to be more tolerant of titration at any speed. CONCLUSIONS: This analysis indicates that faster titration yields faster onset of clinical benefit and is especially practical in the pediatric population, though attempts to accelerate adult titration may still be warranted.
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Epilepsia , Estimulação do Nervo Vago , Adulto , Criança , Frequência Cardíaca , Humanos , Convulsões , Resultado do TratamentoRESUMO
BACKGROUND: Radio-frequency ablation (RFA) for Barrett's oesophagus (BE)-related neoplasia is currently used after endoscopic resection of visible neoplasia. The HALO 360 balloon has been used to ablate long segment BE. The Barrx™ 360 Express RFA self-sizing catheter ('RFA Express') may potentially allow quicker ablation times and improved treatment outcomes. The aim of this paper is to present real world data on the use of the 360 Express Device. METHODS: Centres in the UK and Ireland submitted cases where the RFA Express was used. The primary outcome was regression of BE at 3 months. Secondary outcomes were the rate of symptomatic stricture formation and resolution of intestinal metaplasia (CR-IM) and dysplasia (CR-D) at End of Treatment (EoT). RESULTS: 11 centres submitted 123 consecutive patients. 112 had a follow up endoscopy. The median age was 67 years (IQR 62-75). 3 dosimetries were used. The mean reduction in Circumferential (C) length was 78% ± 36 and mean reduction in Maximal length (M) was 55% ± 36. 17 patients (15%) developed strictures requiring dilation. There was a higher rate of stricture formation when the 12 J energy was used (p < 0.05). 47 patients had EoT biopsies, 40 (85%) had CR-D and 34(76%) had CR-IM. CONCLUSIONS: The RFA 360 Express catheter shows reduction in length of baseline BE at 3 months after index treatment, and eradication of intestinal metaplasia and dysplasia at 12 months similar to other studies with earlier devices. It appears that the symptomatic stricture rate is slightly higher than previous series with the HALO 360 catheter. This study was performed as part of the HALO registry and has been approved by the Research Ethics Committee - MREC Number 08/H0714/27 Local project reference 08/0104 Project ID 15,033 IRAS Number 54678 EudraCT 2009-015980-1. Registered on ISRCTN as below: ISRCTN93069556. https://doi.org/10.1186/ISRCTN93069556.
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Esôfago de Barrett , Ablação por Cateter , Neoplasias Esofágicas , Idoso , Esôfago de Barrett/complicações , Esôfago de Barrett/cirurgia , Ablação por Cateter/métodos , Catéteres , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Humanos , Irlanda , Resultado do Tratamento , Reino UnidoRESUMO
OBJECTIVE: Limited data are available regarding the evolution over time of the rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy implanted with vagus nerve stimulation (VNS) therapy in the United States (from 1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation follow-up period. METHODS: Patient vital status was ascertained using the Centers for Disease Control and Prevention's National Death Index (NDI). An expert panel adjudicated classification of cause of deaths as SUDEP based on NDI data and available narrative descriptions of deaths. We tested the hypothesis that SUDEP rates decrease with time using the Mann-Kendall nonparametric trend test and by comparing SUDEP rates of the first 2 years of follow-up (years 1-2) to longer follow-up (years 3-10). RESULTS: Our cohort included 277 661 person-years of follow-up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a significant decrease in age-adjusted SUDEP rate during follow-up (S = -27 P = .008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P = .002). Sensitivity analyses confirm these findings. SIGNIFICANCE: Our data suggest that SUDEP risk significantly decreases during long-term follow-up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long-term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study.
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Morte Súbita/prevenção & controle , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Vigilância da População , Estimulação do Nervo Vago/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Morte Súbita/epidemiologia , Epilepsia Resistente a Medicamentos/mortalidade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Background and study aims Acetic acid chromoendoscopy (AAC) enhances the ability to correctly identify Barrett's neoplasia, and is increasingly used by both expert and nonexpert endoscopists. Despite its increasing use, there is no validated training strategy to achieve competence. The aims of our study were to develop a validated training tool in AAC-assisted lesion recognition, to assess endoscopists' baseline knowledge of AAC-assisted lesion recognition, and to evaluate the efficacy and impact of this training tool. Methods A validated assessment of 40 images and 20 videos was developed. A total of 13 endoscopists with experience of Barrett's endoscopy but no formal training in AAC were recruited to the study. Participants underwent: baseline assessment 1, online training, assessment 2, interactive seminar, assessment 3. Results Baseline assessment demonstrated a sensitivity of 83â% and a negative predictive value (NPV) of 83â%. The online training intervention significantly improved sensitivity to 95â% and NPV to 94â% (Pâ<â0.01). Further improvement was seen after a 1-day interactive seminar including live cases, with sensitivity increasing to 98â% and NPV to 97â%. Conclusions The data demonstrate the need for training in AAC-assisted lesion recognition as baseline performance, even by Barrett's experts, was poor. The online training and testing tool for AAC for Barrett's neoplasia was successfully developed and validated. The training intervention improved performance of endoscopists to meet ASGE PIVI standards. The training tool increases the endoscopist's degree of confidence in the use of AAC. The training tool also leads to shift in attitudes of endoscopists from Seattle protocol towards AAC-guided biopsy protocol for Barrett's surveillance.
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Ácido Acético/administração & dosagem , Esôfago de Barrett/patologia , Esofagoscopia/educação , Esofagoscopia/normas , Indicadores e Reagentes/administração & dosagem , Biópsia/métodos , Competência Clínica , Esofagoscopia/métodos , Humanos , Desenvolvimento de ProgramasRESUMO
BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77â% vs. 47â%; Pâ<â0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88â% and 76â%, respectively; IMC 87â% and 75â%, respectively; Pâ=â0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8â%, IMC 3.8â%; Pâ=â0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (Pâ=â0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (Pâ=â0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.
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Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ablação por Cateter , Neoplasias Esofágicas/cirurgia , Esôfago/cirurgia , Lesões Pré-Cancerosas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Mucosa/cirurgia , Lesões Pré-Cancerosas/patologia , Sistema de Registros , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72% with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69 years; 81% male]), treated at 19 centers in the United Kingdom from July 2008 through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm). Patients' nodules were removed by endoscopic mucosal resection, and the patients then underwent RFA every 3 months until all areas of BE were ablated or cancer developed. Biopsies were collected 12 months after the first RFA; clearance of HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of patients, all dysplasia from 81%, and BE from 62% at the 12-month time point, after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was 15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE = 0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal resection before RFA did not provide any benefit. Invasive cancer developed in 10 patients (3%) by the 12-month time point and disease had progressed in 17 patients (5.1%) after a median follow-up time of 19 months. Symptomatic strictures developed in 9% of patients and were treated by endoscopic dilatation. Nineteen months after therapy began, 94% of patients remained clear of dysplasia. CONCLUSIONS: We analyzed data from a large series of patients in the United Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.
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Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ablação por Cateter , Neoplasias Esofágicas/cirurgia , Esofagoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/cirurgia , Estadiamento de Neoplasias , Sistema de Registros , Resultado do TratamentoRESUMO
Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.
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Córtex Pré-Frontal , Transtornos de Estresse Pós-Traumáticos , Substância Branca , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/patologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/fisiopatologia , Masculino , Adulto , Feminino , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/patologia , Terapia Implosiva/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Resultado do TratamentoRESUMO
We describe the optimization and scale-up of two consecutive reaction steps in the synthesis of bio-derived alkoxybutenolide monomers that have been reported as potential replacements for acrylate-based coatings (Sci. Adv.2020, 6, eabe0026). These monomers are synthesized by (i) oxidation of furfural with photogenerated singlet oxygen followed by (ii) thermal condensation of the desired 5-hydroxyfuranone intermediate product with an alcohol, a step which until now has involved a lengthy batch reaction. The two steps have been successfully telescoped into a single kilogram-scale process without any need to isolate the 5-hydroxyfuranone between the steps. Our process development involved FTIR reaction monitoring, FTIR data analysis via 2D visualization, and two different photoreactors: (i) a semicontinuous photoreactor based on a modified rotary evaporator, where FTIR and 2D correlation spectroscopy (2D-COS) revealed the loss of the methyl formate coproduct, and (ii) our fully continuous Taylor Vortex photoreactor, which enhanced the mass transfer and permitted the use of near-stoichiometric equivalents of O2. The use of in-line FTIR monitoring and modeling greatly accelerated process optimization in the Vortex reactor. This led to scale-up of the photo-oxidation in 85% yield with a projected productivity of 1.3 kg day-1 and a space-time yield of 0.06 mol day-1 mL-1. Higher productivities could be achieved while sacrificing yield (e.g., 4 kg day-1 at 40% yield). The use of superheated methanol at 200 °C in a pressurized thermal flow reactor accelerated the second step, the thermal condensation of 5-hydroxyfuranone, from a 20 h batch reflux reaction (0.5 L, 85 g) to a space time of <1 min in a reactor only 3 mL in volume operating with projected productivities of >700 g day-1. Proof of concept for telescoping the two steps was established with an overall two-step yield of 67%, producing a process with a projected productivity of 1.1 kg day-1 for the methoxybutenolide monomer without any purification of the 5-hydroxyfuranone intermediate.
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BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS: We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.
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Adenocarcinoma/terapia , Esôfago de Barrett/terapia , Ablação por Cateter , Neoplasias Esofágicas/terapia , Esofagectomia , Esofagoscopia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/mortalidade , Esôfago de Barrett/complicações , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/mortalidade , Técnica Delphi , Progressão da Doença , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Humanos , RiscoRESUMO
For people with post-traumatic stress disorder (PTSD), recall of traumatic memories often displays as intrusions that differ profoundly from processing of 'regular' negative memories. These mnemonic features fueled theories speculating a unique cognitive state linked with traumatic memories. Yet, to date, little empirical evidence supports this view. Here we examined neural activity of patients with PTSD who were listening to narratives depicting their own memories. An intersubject representational similarity analysis of cross-subject semantic content and neural patterns revealed a differentiation in hippocampal representation by narrative type: semantically similar, sad autobiographical memories elicited similar neural representations across participants. By contrast, within the same individuals, semantically similar trauma memories were not represented similarly. Furthermore, we were able to decode memory type from hippocampal multivoxel patterns. Finally, individual symptom severity modulated semantic representation of the traumatic narratives in the posterior cingulate cortex. Taken together, these findings suggest that traumatic memories are an alternative cognitive entity that deviates from memory per se.
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Memória Episódica , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Rememoração Mental , Cognição , SemânticaRESUMO
NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be reconsolidated in an altered form. This concept might have significant clinical implications in treating PTSD. In this pilot study we tested the potential of a single infusion of ketamine, followed by brief exposure therapy, to enhance post-retrieval extinction of PTSD trauma memories. 27 individuals diagnosed with PTSD were randomly assigned to receive either ketamine (0.5 mg/kg 40 min; N = 14) or midazolam (0.045 mg/kg; N = 13) after retrieval of the traumatic memory. 24 h following infusion, participants received a four-day trauma-focused psychotherapy. Symptoms and brain activity were assessed before treatment, at the end of treatment, and at 30-day follow-up. Amygdala activation to trauma scripts (a major biomarker of fear response) served as the main study outcome. Although PTSD symptoms improved equally in both groups, post-treatment, ketamine recipients showed a lower amygdala (-0.33, sd = 0.13, 95%HDI [-0.56,-0.04]) and hippocampus (-0.3 (sd = 0.19), 95%HDI [-0.65, 0.04]; marginal effect) reactivation to trauma memories, compared to midazolam recipients. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus (-0.28, sd = 0.11, 95%HDI [-0.46, -0.11]), with no change in amygdala-vmPFC connectivity. Moreover, reduction in fractional anisotropy in bi-lateral uncinate fasciculus was seen in the Ketamine recipients compared with the midazolam recipients (right: post-treatment: -0.01108, 95% HDI [-0.0184,-0.003]; follow-up: -0.0183, 95% HDI [-0.02719,-0.0107]; left: post-treatment: -0.019, 95% HDI [-0.028,-0.011]; follow-up: -0.017, 95% HDI [-0.026,-0.007]). Taken together it is possible that ketamine may enhance post-retrieval extinction of the original trauma memories in humans. These preliminary findings show promising direction toward the capacity to rewrite human traumatic memories and modulate the fear response for at least 30 days post-extinction. When combined with psychotherapy for PTSD, further investigation of ketamine dose, timing of administration, and frequency of administration, is warranted.
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Ketamina , Transtornos de Estresse Pós-Traumáticos , Humanos , Extinção Psicológica , Ketamina/farmacologia , Midazolam/uso terapêutico , Projetos Piloto , Psicoterapia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológicoRESUMO
Posttraumatic stress disorder (PTSD) is associated with changes in fear learning and decision-making, suggesting involvement of the brain's valuation system. Here we investigate the neural mechanisms of subjective valuation of rewards and punishments in combat veterans. In a functional MRI study, male combat veterans with a wide range of posttrauma symptoms (N = 48, Clinician Administered PTSD Scale, CAPS-IV) made a series of choices between sure and uncertain monetary gains and losses. Activity in the ventromedial prefrontal cortex (vmPFC) during valuation of uncertain options was associated with PTSD symptoms, an effect which was consistent for gains and losses, and specifically driven by numbing symptoms. In an exploratory analysis, computational modeling of choice behavior was used to estimate the subjective value of each option. The neural encoding of subjective value varied as a function of symptoms. Most notably, veterans with PTSD exhibited enhanced representations of the saliency of gains and losses in the neural valuation system, especially in ventral striatum. These results suggest a link between the valuation system and the development and maintenance of PTSD, and demonstrate the significance of studying reward and punishment processing within subject.
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Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Punição , Córtex Pré-Frontal/diagnóstico por imagem , Recompensa , Medo , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodosRESUMO
Hyperactivation of amygdala is a neural marker for post-traumatic stress disorder (PTSD) and improvement in control over amygdala activity has been associated with treatment success in PTSD. In this randomized, double-blind clinical trial we evaluated the efficacy of a real-time fMRI neurofeedback intervention designed to train control over amygdala activity following trauma recall. Twenty-five patients with PTSD completed three sessions of neurofeedback training in which they attempted to downregulate the feedback signal after exposure to personalized trauma scripts. For subjects in the active experimental group (N = 14), the feedback signal was from a functionally localized region of their amygdala associated with trauma recall. For subjects in the control group (N = 11), yoked-sham feedback was provided. Changes in control over the amygdala and PTSD symptoms served as the primary and secondary outcome measurements, respectively. We found significantly greater improvements in control over amygdala activity in the active group than in the control group 30-days following the intervention. Both groups showed improvements in symptom scores, however the symptom reduction in the active group was not significantly greater than in the control group. Our finding of greater improvement in amygdala control suggests potential clinical application of neurofeedback in PTSD treatment. Thus, further development of amygdala neurofeedback training in PTSD treatment, including evaluation in larger samples, is warranted.
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Neurorretroalimentação , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/terapia , Imageamento por Ressonância Magnética , Neurorretroalimentação/fisiologia , Regulação para Baixo , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologiaRESUMO
BACKGROUND: While vagus nerve stimulation (VNS) has been in use for over two decades, little professional guidance exists to describe dosing and titration of therapy which is the consequence of a limited amount of evidence developed during the pre-market phase of therapy development. Post-market surveillance of dosing practice has revealed significant deviations from dosing and titration guidance offered by professional societies as well as the manufacturer. OBJECTIVE: This analysis aims to identify a target dose for VNS Therapy in Epilepsy. METHODS: Herein, VNS clinical outcomes are linked to the patient-specific dosing parameters for each study visit (n = 1178 patients). A generalized linear mixed model was built to ascertain the relationship between key stimulation parameters (i.e., Output Current, Pulse Width, Signal Frequency, and Duty Cycle) and clinical response, defined as a 50% or greater reduction in seizure frequency from baseline. Other demographic parameters of interest, such as duration of epilepsy and age at implant, were also explored. RESULTS: A population level target output current and duty cycle for VNS therapy for epilepsy was identified as 1.61 mA and 17.1% duty cycle. Patients with shorter duration of epilepsy were identified to have a higher likelihood to respond to VNS therapy (p < 0.001). While patients who were on the therapy longer were more likely to respond to the therapy, the effect did not interact with the dosing settings - suggesting that patients who have been chronically underdosed may still benefit from achieving the target dose. CONCLUSION: An opportunity exists to improve upon VNS outcomes by aligning clinical practice around this evidence-based target dose.
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Epilepsia Resistente a Medicamentos , Epilepsia , Estimulação do Nervo Vago , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/terapia , Frequência Cardíaca , Humanos , Convulsões/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Insulinoma is the most common neuroendocrine neoplasm of the pancreas, characterised by hypoglycaemic symptoms. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and ethanol ablation (EUS-EA) are novel methods for treating insulinoma.We aimed to perform a systematic review to assess the efficacy and safety of EUS-guided ablation techniques for pancreatic insulinomas. METHODS: We systematically searched for articles detailing EUS-guided ablations of insulinomas. We performed a qualitative analysis and summarised data on the efficacy and safety of EUS-RFA and EUS-EA techniques. RESULTS: In total, we identified 35 case reports and case series describing 75 patients with insulinomas treatment with EUS-guided ablation. Twenty-seven patients were treated with EUS-RFA, 47 patients with EUS-EA, and 1 patient received EUS-EA and EUS-RFA in the same session. In total, 84 insulinomas were ablated (EUS-RFA: 31, EUS-EA: 53). Most insulinomas were in the head of the pancreas (40%). The clinical success rate for EUS-guided ablation techniques was 98.5%. The median glucose level was 1.95 (Q1-Q3: 1.69-2.13) mmol/L before ablation compared to 6.20 (Q1-Q3: 5.30-7.05) mmol/L after treatment. The median insulin and C-peptide levels before and after RFA/EA were 230 (Q1-Q2: 120-257) pmol/L and 41 (Q1-Q2 35-42) pmol/L; 2077 (Q1-Q2 1644-2459) pmol/L and 819 (Q1-Q2 696-1072) pmol/L, respectively. There were eleven adverse events: seven abdominal pain, two mild acute pancreatitis, one necrotising acute pancreatitis and one local hematoma. All patients recovered, and there were no periprocedural deaths. CONCLUSIONS: EUS-guided ablation of insulinoma seems to be a safe and effective treatment and is an alternative to surgical resection in selected cases.
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OBJECTIVES: Early physical therapy (PT) with specific stabilization training has been shown to benefit individuals after lumbar spinal surgery but has not been studied in patients after cervical spine surgery. The primary purpose of this study was to compare clinical outcomes between early cervical spine stabilizer (ECS) training and usual care (UC) in patients after anterior cervical discectomy and fusion (ACDF) surgery. The secondary purpose was to determine test-retest reliability of strength and endurance tests of cervical spinal stabilizers in this patient population. METHODS: Forty participants who were scheduled for ACDF surgery were randomized into either the ECS group or the UC group. After surgery, participants received their assigned group intervention during their hospital stay and continued their assigned intervention for 12 weeks. All participants had phone follow-ups twice during the first 6 weeks to address questions or problems. Clinical outcome measures including pain level using the Numeric Pain Rating Scale (NPRS), disability level using the Neck Disability Index (NDI), Craniocervical Flexor Strength (CCF-S), and Craniocervical Flexor Endurance (CCF-E) were collected three times: before surgery and 6 and 12 weeks after surgery. Test-retest reliability was assessed in the first 10 participants. RESULTS: There was no significant interaction between the groups over time for any of the outcome measures. However, all participants made significant improvements in all four outcome measures at 6 and 12 weeks post surgery. The results showed good-to-excellent test-retest reliability for the CCF-S and CCF-E tests. CONCLUSIONS: Both ECS training and UC resulted in the same amount of improvement at 6 and 12 weeks; therefore, both therapy approaches appear to have similar and positive effects on patients in their first 3 months of recovery after ACDF. Both the CCF-S and CCF-E tests can be used reliably to assess the strength and endurance of the cervical spinal stabilizers for patients after ACDF surgery. The study was registered with the ClinicalTrials.gov (NIH, U.S. National Library of Medicine, identifier # NCT01519115) Protocol Registration system.