This study aimed to analyze published studies regarding the usefulness of Acceptance and Commitment Therapy in the treatment of oncological patients. A systematic review of the literature was ...conducted using the Web of Science, Google Scholar and Dialnet (2000-2016). Nineteen articles fulfilled the inclusion criteria. Those patients who received interventions based on Acceptance and Commitment Therapy showed a better emotional state and quality of life and greater psychological flexibility. Acceptance and Commitment Therapy proved to be useful in the psychological treatment of oncological patients. However, the heterogeneity and limitations of the studies, principally with regard to sample characteristics, study design and manner in which mechanisms responsible for changes are evaluated, make further studies necessary with a view to ascertaining what patient and/or intervention characteristics might improve results. Randomized controlled trials comparing the efficacy of Acceptance and Commitment Therapy with no treatment, with treatment with placebo and with other efficacious therapies, including a study of medium- and long-term results, would be of particular interest.
Specific phobias are a common anxiety disorder that deteriorates the lives of people who suffer from them. To reduce the symptoms produced by this mental disorder exposure therapies have been used. ...However, low- and middle-income countries, including Mexico, have the lowest rate of treatment due to multiple barriers that prevent addressing mental health problems. Self-applied treatments have been explored in previous studies, nevertheless, high dropout rates are a common problem in this kind of treatment. An alternative is using immersive self-applied treatments that could help increase adherence to the treatment. This article aims to present a study protocol to explore the feasibility of an Internet self-applied exposure treatment for rat phobias, using four types of immersive multimedia elements: images, videos, video games, and 360° videos. Also, the satisfaction and perception of a Virtual Therapy Assistant (VTA) that provides information and support to the user are described. The study protocol will compare two groups of participants, one on the waiting list, and the other will receive the self-applied treatment for rat phobia supported by the VTA. For this study, 45 participants will be recruited and the evaluation measures will be taken at four different times: baseline, post-treatment, and follow-ups at 3 and 6 months. The levels of anxiety and avoidance of the user manifested during the exposure to the multimedia elements, the improvement of the user's clinical symptoms, the level of satisfaction, the perception of effectiveness, and ease of use of the self-applied system will be evaluated. This study is expected to support the viability of self-applied treatment for rat phobias and the use of a VTA, showing the impact on treatment adherence. To the best of our knowledge, this is the first study to explore an exposure treatment for rats using different multimedia elements with the support of a VTA. The work will serve as a basis for the development of new virtual assistants that help in the treatment of other types of specific phobias. This research has been registered in Clinical Trials NCT (NCT05081323).
Cancer cells' ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined ...migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage.
Hypoglycin A (HGA) toxicity, following ingestion of material from certain plants, is linked to an acquired multiple acyl-CoA dehydrogenase deficiency known as atypical myopathy, a commonly fatal form ...of equine rhabdomyolysis seen worldwide. Whilst some plants are known to contain this toxin, little is known about its function or the mechanisms that lead to varied HGA concentrations between plants. Consequently, reliable tools to detect this amino acid in plant samples are needed. Analytical methods for HGA detection have previously been validated for the food industry, however, these techniques rely on chemical derivatisation to obtain accurate results at low HGA concentrations. In this work, we describe and validate a novel method, without need for chemical derivatisation (accuracy = 84-94%; precision = 3-16%; reproducibility = 3-6%; mean linear range R2 = 0.999). The current limit of quantitation for HGA in plant material was halved (from 1μg/g in previous studies) to 0.5μg/g. The method was tested in Acer pseudoplatanus material and other tree and plant species. We confirm that A. pseudoplatanus is most likely the only source of HGA in trees found within European pastures.
The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery ...are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production.
Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants ...generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.
Background
Measurement of hypoglycin A (HGA) and its toxic metabolite, methylenecyclopropylacetic acid (MCPA), in equine serum confirms a diagnosis of atypical myopathy (AM), a pasture‐associated ...toxic rhabdomyolysis with high mortality linked to the ingestion of Acer trees plant material. Supportive diagnostic tests include plasma acyl‐carnitine profiling and urine organic acid testing, but these are not specific for AM. Previously reported HGA and MCPA analytical techniques used liquid chromatography–mass spectrometry (LC‐MS) with a derivatising step, but the latter prolongs testing and increases costs.
Objectives
To develop a rapid LCMS method for detection of serum and tissue HGA and MCPA that enables expedited diagnosis for horses with AM.
Study design
Analytical test validation.
Methods
Validation parameters to industry standards using as criteria precision, accuracy, linearity, reproducibility and stability in analyte‐spiked samples were calculated on 9‐calibration points and 3 different validation concentrations in both serum and muscle tissue.
Results
The test was successfully validated for the detection of HGA and MCPA‐carnitine in equine serum and muscle. Test linearity was excellent (r2 = .999), accuracy was very good for both analytes (93%‐108%), precision did not exceed 10% coefficient of variation and reproducibility met the requirements of the Horwitz equation. Stability was unaffected by storage at a range of temperatures.
Main limitations
The spectrum of the tested analytes was limited to only two relevant analytes in favour of a quick and easy analysis. Linearity of the muscle method was not evaluated as calibration curves were not produced in this matrix.
Conclusion
We report an optimised, simplified and validated method for detection of HGA and MCPA‐carnitine in equine serum and muscle suitable for rapid diagnosis of suspected AM cases. The serum‐based test should also enable risk assessment of toxin exposure in cograzing horses and assessment of horses with undiagnosed myopathies, while the tissue detection test should help to confirm cases post‐mortem and to determine toxin distribution, metabolism and clearance across different tissues.
Background Although empiric exclusion from the diet of the 6 food groups most likely to trigger allergies achieves eosinophilic esophagitis (EoE) remission in children, data on its prolonged efficacy ...and effects on adults are lacking. Objective We sought to evaluate the efficacy of a 6-food elimination diet in inducing and maintaining prolonged remission in patients with adult EoE. Methods Sixty-seven consecutive patients with adult EoE were prospectively recruited and treated exclusively with a diet avoiding cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy for 6 weeks. Subsequent challenge was undertaken by sequentially reintroducing all excluded single foods, followed by endoscopy and biopsies, which were developed every 6 weeks in case of response (eosinophil peak count reduction to <15/high-power field hpf). A food was considered a trigger for EoE and removed from the diet if pathologic eosinophilic infiltration (≥15 eosinophils/hpf) reappeared. Food-specific serum IgE measurements and skin prick tests were performed before initiating the diet. Results Forty-nine (73.1%) patients exhibited significantly reduced eosinophil peak counts (<15 eosinophils/hpf) before sequential single-food reintroduction. A single offending food antigen was identified in 35.71% of patients, 2 food triggers were identified in 30.95%, and 3 or more food triggers were identified in 33.3%. Cow's milk was the most common food antigen (61.9%), followed by wheat (28.6%), eggs (26.2%), and legumes (23.8%). Prior allergy tests showed no concordance with food-reintroduction challenge results. All patients who continued to avoid the offending foods maintained histopathologic and clinical EoE remission for up to 3 years. Conclusions An empiric 6-food elimination diet effectively induced remission of active adult EoE, which was maintained for up to 3 years with individually tailored, limited exclusion diets.
Summary
Background
Intracarotid injections are a well‐recognised complication of jugular injections in the horse; however, little information is available about outcome and complications.
Objectives
...The aim of this study was to describe venipuncture techniques and short‐ and longer‐term complications related to intracarotid injections.
Study design
Case series.
Methods
The survey was distributed through the American College of Veterinary Internal Medicine (ACVIM) mailing list and a veterinary social media site. Data collected in the questionnaire included injection technique, drug administered, personnel performing the injection, clinical signs and short‐ and longer‐term complications.
Results
Accidental intracarotid injections were most commonly performed by veterinarians (n = 9/13). The majority of reported accidental intracarotid injections occurred during routine sedation in healthy horses (n = 8/13) and occurred when the jugular vein was accessed at the middle jugular groove (n = 6/13). Most events occurred while using longer needles (1.5 inches; n = 10/13) of 20G calibre (n = 9/13), attached to the syringe (n = 11/13) and against jugular blood flow (n = 11/13). Short‐term injuries included superficial abrasions (n = 13/13) and cardiac ailments (3/13). One of the 15 horses described in this report died. Longer‐term complications were not reported for the remaining 14 horses.
Main limitations
Potential selection, recall and response bias and putative risk factors identified cannot be correlated with an increased risk of carotid injection without a control group.
Conclusion
Accidental intracarotid injections led to seizures but rarely resulted in death of the case. Premonitory clinical signs occurred while or soon after injection and can be used for early identification of this inadvertent injection and to establish safety measures for the horse and handlers.
Summary
Although follicular lymphoma (FL) patients relapsing within 24 months after first‐line treatment (POD24) have a poor prognosis, some cases show notable survival after first relapse (SF1R). We ...aimed to characterize the POD24 FL population and to identify the main prognostic factors at progression. We selected 162 POD24 patients (80F; median age at first relapse 59 years) from a cohort of 1067 grades 1‐3a FL‐treated patients. The remaining 905 patients treated with first‐line immunochemotherapy and diagnosed during the same period were used to compare outcomes in terms of survival. After a median follow‐up of 11.0 years, 96 patients died (10y‐SF1R of 40%). Age over 60 years (p < 0.001), high lactate dehydrogenase (LDH) (p < 0.001), haemoglobin (Hb) less than 120 g/L (p < 0.001), advanced stage (p < 0.001), high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) (p < 0.001), histological transformation (HT) (p < 0.001) and reaching less than complete response (CR) after salvage therapy (p < 0.001), predicted poor SF1R at relapse. In multivariate analysis only high‐risk FLIPI and HT maintained prognostic significance for SF1R. POD24 patients not transformed and with low/intermediate FLIPI at relapse behaved better than the remaining cases. POD24 patients showed an excess mortality of 38% compared to the general population. Although outcome of POD24 FL patients is poor, a considerable group of them (low/intermediate FLIPI and not transformed at first relapse) behave better.
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