Unravelling the mechanisms behind the short-term effects of dry needling: new insights from a mediation analysis with repeatedly measured mediators and outcomes.

OBJECTIVE: to explore the causal pathways underlying the short-term effects of deep dry needling (DDN) in people with chronic neck pain. DESIGN: explanatory longitudinal mediation analysis with repeatedly measured mediators and outcomes. SETTING: primary care setting PARTICIPANTS: 128 patients with chronic neck pain. INTERVENTIONS: Participants were randomized in 2 groups; DDN of the neck muscles combined with stretching (N = 64) and stretching alone (N=64). OUTCOME MEASURES(S): Two outcomes (pain intensity and neck pain-related disability) and 3 candidate mediators (local pain pressure thresholds (PPTs), cervical range of motion (ROM) and neck muscle strength) were included. Pain intensity was also included as a competing mediator in the mediation analysis for disability. Mediators and outcomes were measured at three timepoints; post-intervention and 2- and 4-week follow-up. Age, gender and the baseline values of the outcome and mediators were included as pre-treatment mediator-outcome confounders. RESULTS: reductions in pain intensity strongly mediated the short-term effects of DDN on disability, from post-intervention to 4-week follow-up. In addition, the attenuation of local hypersensitivity (via increasing PPTs) moderately mediated reductions in pain intensity at each timepoint. On the other hand, gains in cervical ROM contributed to reducing neck pain-related disability. Changes in muscle strength did not lead to better outcomes. CONCLUSION: this novel study demonstrated that DDN effect on neck pain-related disability is strongly driven by the analgesic effects of this physical therapy modality. Increasing PPTs and cervical ROM seem to be also part of the mechanisms behind DDN's effect.

Metabolic Changes Induced by Bariatric Surgery May be Mediated by PAI-1 and PCSK9 Crosstalk.

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Gray Matter Adaptations to Chronic Pain in People with Whiplash-Associated Disorders are Partially Reversed After Treatment: A Voxel-based Morphometry Study.

Gray matter (GM) changes are often observed in people with chronic spinal pain, including those with chronic whiplash-associated disorders (CWAD). These GM adaptations may be reversed with treatment, at least partially. Pain neuroscience education combined with exercise (PNE+Exercise) is an effective treatment, but its neural underlying mechanisms still remain unexplored in CWAD. Here, we performed both cross-sectional and longitudinal voxel-based morphometry to 1) identify potential GM alterations in people with CWAD (n = 63) compared to age- and sex-matched pain-free controls (n = 32), and 2) determine whether these GM alterations might be reversed following PNE+Exercise (compared to conventional physiotherapy). The cross-sectional whole-brain analysis revealed that individuals with CWAD had less GM volume in the right and left dorsolateral prefrontal cortex and left inferior temporal gyrus which was, in turn, associated with higher pain vigilance. Fifty individuals with CWAD and 29 pain-free controls were retained in the longitudinal analysis. GM in the right dorsolateral prefrontal cortex increased after treatment in people with CWAD. Moreover, the longitudinal whole-brain analysis revealed that individuals with CWAD had decreases in GM volumes of the left and right central operculum and supramarginal after treatment. These changes were not specific to treatment modality and some were not observed in pain-free controls over time. Herewith, we provide the first evidence on how GM adaptations to CWAD respond to treatment. PERSPECTIVE: This article presents which gray matter adaptations are present in people with chronic pain after whiplash injuries. Then, we examine the treatment effect on these alterations as well as whether other neuroplastic effects on GM following treatment occur.

Energy painting: helium-beam radiography with thin detectors and multiple beam energies.

Objective.Compact ion imaging systems based on thin detectors are a promising prospect for the clinical environment since they are easily integrated into the clinical workflow. Their measurement principle is based on energy deposition instead of the conventionally measured residual energy or range. Therefore, thin detectors are limited in the water-equivalent thickness range they can image with high precision. This article presents ourenergy paintingmethod, which has been developed to render high precision imaging with thin detectors feasible even for objects with larger, clinically relevant water-equivalent thickness (WET) ranges.Approach.A detection system exclusively based on pixelated silicon Timepix detectors was used at the Heidelberg ion-beam therapy center to track single helium ions and measure their energy deposition behind the imaged object. Calibration curves were established for five initial beam energies to relate the measured energy deposition to WET. They were evaluated regarding their accuracy, precision and temporal stability. Furthermore, a 60 mm × 12 mm region of a wedge phantom was imaged quantitatively exploiting the calibrated energies and five different mono-energetic images. These mono-energetic images were combined in a pixel-by-pixel manner by averaging the WET-data weighted according to their single-ion WET precision (SIWP) and the number of contributing ions.Main result.A quantitative helium-beam radiograph of the wedge phantom with an average SIWP of 1.82(5) % over the entire WET interval from 150 mm to 220 mm was obtained. Compared to the previously used methodology, the SIWP improved by a factor of 2.49 ± 0.16. The relative stopping power value of the wedge derived from the energy-painted image matches the result from range pullback measurements with a relative deviation of only 0.4 %.Significance.The proposed method overcomes the insufficient precision for wide WET ranges when employing detection systems with thin detectors. Applying this method is an important prerequisite for imaging of patients. Hence, it advances detection systems based on energy deposition measurements towards clinical implementation.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Entrenamiento de la fuerza en niños y adolescentes: Una Revisión sistemática años 2018-2022 / Strength training in children and adolescents: A systematic review years 2018-2022

Con el pasar del tiempo y especialmente en los últimos años el entrenamiento de la fuerza en niños y adolescentes ha venido tomando fuerza, convirtiéndose en uno de los componentes más importantes en el desarrollo de las capacidades físicas y motrices. El objetivo es Identificar las tendencias más recientes en lo referente a la prescripción del entrenamiento de la fuerza en niños y adolescentes la metodología: se desarrollo una revisión sistemática en la que fueron analizados 648 artículos de los cuales sólo 10 fueron seleccionados dada su relevancia y relación con el tema, además dichos artículos fueron extraídos de las bases de datos: Google Académico, Redalyc, Dialnet, y Scielo. En los resultados se pudo identificar en la revisión, (N=11) investigaciones experimentales cuantitativas y (N=15) estudios de revisión (cualitativas), así como un total de (n=234) participantes de ambos sexos en las intervenciones experimentales y un total de (n=139) estudios consultados en los artículos de revisión sistemática. En las conclusiones se logró identificar que el entrenamiento con pesos libres, y peso corporal son la tendencia más usada a la hora de prescribir entrenamiento de la fuerza. Consigo, se destaca que son los métodos de entrenamiento con pesas y bandas elásticas los implementos más utilizados para llevar a cabo su realización. La frecuencia recomendada es de 2 a 3 días por semana. El volumen que se destaca es de 2 a 3 series y 6 a 15 repeticiones por ejercicio donde la intensidad que prevalece son los porcentajes del 60% al 85% por ciento de 1RM o una intensidad moderada en la escala del esfuerzo percibido (AU)

With the passing of time and especially in recent years, strength training in children and adolescents has been gaining strength, becoming one of the most important components in physical and motor development. The objective is to identify the most recent trends regarding the prescription of strength training in children and adolescents. The methodology: a systematic review was developed in which 648 articles were analyzed, of which only 10 were selected given their relevance and relationship. with the subject, in addition said articles were extracted from the databases: Google Scholar, Redalyc, Dialnet, and Scielo. In the results it was possible to identify in the review, (N=11) quantitative experimental investigations and (N=15) review studies (qualitative), as well as a total of (n=234) participants of both sexes in the experimental interruptions and a total of (n=139) studies consulted in the systematic review articles. In the conclusions it will be identified that training with free weights and body weight are the most used trend when prescribing strength training. With it, it stands out that the methods of training with weights and elastic bands are the most used implements to carry out their realization. The recommended frequency is 2 to 3 days per week weeks. The volume that stands out is 2 to 3 sets and 6 to 15 repetitions per exercise where the prevailing intensity is 60% to 85% percent of 1RM or moderate intensity on the perceived exertion scale (AU)

A Scan of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants of Baseline FVIII Inhibitor Status in Hemophilia-A.

Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)" and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8-mutational-heterogeneity. The baseline-FEI-status of 450 North American PATH subjects-206 with black-African-ancestry and 244 with white-European-ancestry-was the dependent variable. The F8-mutation-data and a genetic-relatedness matrix were incorporated into a binary linear-mixed model of genetic association with baseline-FEI-status. We adopted a gene-centric-association-strategy to scan, as candidates, pleiotropic-IMD-genes implicated in the development of either ³2 autoimmune-/autoinflammatory-disorders (AADs) or ³1 AAD and FEIs. Baseline-FEI-status was significantly associated with SNPs assigned to NOS2A (rs117382854; p=3.2E-6) and B3GNT2 (rs10176009; p=5.1E-6), which have functions in anti-microbial-/-tumoral-immunity. Among IMD-genes implicated in FEI-risk previously, we identified strong associations with CTLA4 assigned SNPs (p=2.2E-5). The F8-mutation-effect underlies ~15% of the total heritability for baseline-FEI-status. Additive genetic heritability and SNPs in IMD-genes account for >50% of the patient-specific variability in baseline-FEI-status. Race is a significant determinant independent of F8-mutation-effects and non-F8-genetics.

Reductions in kinesiophobia and distress after pain neuroscience education and exercise lead to favourable outcomes: a secondary mediation analysis of a randomized controlled trial in primary care.

ABSTRACT: Pain neuroscience education combined with exercise (PNE + exercise) is an effective treatment for patients with chronic spinal pain. Yet, however, little is known about its underlying therapeutic mechanisms. Thus, this study aimed to provide the first insights by performing a novel mediation analysis approach in a published randomized controlled trial in primary care where PNE + exercise was compared with standard physiotherapy. Four mediators (catastrophizing, kinesiophobia, central sensitization-related distress, and pain intensity) measured at postintervention and 3 outcomes (disability, health-related quality of life, and pain medication intake) measured at 6-month follow-up were included into the analysis. The postintervention measure of each outcome was also introduced as a competing candidate mediator in each respective model. In addition, we repeated the analysis by including all pairwise mediator-mediator interactions to allow the effect of each mediator to differ based on the other mediators' values. Postintervention improvements in disability, medication intake, and health-related quality of life strongly mediated PNE + exercise effects on each of these outcomes at 6-month follow-up, respectively. Reductions in disability and medication intake were also mediated by reductions in kinesiophobia and central sensitization-related distress. Reductions in kinesiophobia also mediated gains in the quality of life. Changes in catastrophizing and pain intensity did not mediate improvements in any outcome. The mediation analyses with mediator-mediator interactions suggested a potential effect modification rather than causal independence among the mediators. The current results, therefore, support the PNE framework to some extent as well as highlight the need for implementing the recent approaches for mediation analysis to accommodate dependencies among the mediators.

Principales modificaciones asociadas a la esplenectomía / Main modifications associated with splenectomy

Introducción. El bazo es un órgano linfoide implicado en el reconocimiento antigénico, la depuración de patógenos y la remoción de eritrocitos envejecidos o con inclusiones citoplasmáticas. La esplenectomía es una técnica utilizada tanto para el diagnóstico (linfomas), el tratamiento (trombocitopenia inmune, anemia hemolítica adquirida) y la curación (microesferocitosis hereditaria) de diversas enfermedades. Métodos. Describir los principales cambios hematológicos y complicaciones asociadas al procedimiento de esplenectomía. Discusión. Los cambios posteriores a la esplenectomía pueden ser inmediatos, como la aparición de cuerpos de Howell-Jolly, la trombocitosis y la presencia de leucocitosis durante las primeras dos semanas. Otras complicaciones tempranas incluyen la presencia de trombosis, en especial en pacientes con factores de riesgo secundarios (edad, sedentarismo, manejo hospitalario, obesidad) o un estado hipercoagulable (diabetes, cáncer, trombofilia primaria), siendo tanto el flujo de la vena porta como el volumen esplénico los principales factores de riesgo para su aparición. Las complicaciones tardías incluyen la alteración en la respuesta inmune, aumentando el riesgo de infecciones por bacterias encapsuladas, en conjunto con una reducción en los niveles de IgM secundario a la ausencia de linfocitos B a nivel de bazo. Debido al riesgo de infecciones, principalmente por Streptococcus pneumoniae, la esplenectomía parcial se ha considerado una opción. Conclusión. Una adecuada valoración de la indicación de esplenectomía y la identificación precoz de complicaciones posoperatorias son fundamentales para reducir la mortalidad asociada a la esplenectomía

Introduction. The spleen is a lymphoid organ involved in antigen recognition, pathogen clearance, and removal of aged erythrocytes or those with cytoplasmic inclusions. Splenectomy is a technique used for diagnosis (lymphomas), treatment (immune thrombocytopenia, acquired hemolytic anemia), and cure (hereditary microspherocytosis) of various diseases. Methods. To describe the main hematological changes and complications associated with the splenectomy procedure. Discussion. Changes after splenectomy can be considered immediate: the appearance of Howell-Jolly bodies, thrombocytosis, and leukocytosis during the first two weeks. Other complications include the presence of thrombosis, especially in patients with risk factors (age, sedentary lifestyle, long hospital stay, obesity) or a hypercoagulable state (diabetes, cancer, primary thrombophilia), with both portal vein flow and splenic volume being the main risk factors for its appearance. Late complications include altered immune response, increased risk of infections by encapsulated bacteria, and a reduction in IgM levels secondary to the absence of B lymphocytes in the spleen; due to the risk of diseases mainly by Streptococcus pneumoniae, partial splenectomy has been considered an option. Conclusion. An adequate assessment of the indication for splenectomy and the early identification of complications are essential to reduce the mortality associated with splenectomy

Neural processing of pain-related distress to neck-specific movements in people with chronic whiplash-associated disorders.

ABSTRACT: Pain-related distress contributes to long-term disability in chronic whiplash-associated disorders. Recently, neuroimaging studies have revealed altered neural responses to viewing pictures of movements associated with back pain in key regions for threat and affective processing. In this study, we examined neural correlates of imagining neck-specific movements designed to elicit pain-related distress in individuals with whiplash-associated disorders (n = 63) when compared with that in sex-matched pain-free controls (n = 32). In the scanner, participants were presented with neck-specific movement-related pictures divided into 3 categories (high fear, moderate-fear, and neutral control pictures) and asked to imagine how they would feel if they were performing the movement. Whole-brain analyses revealed greater differential activation (high-fear vs neutral) in individuals with whiplash-associated disorders when compared with that in pain-free controls in 6 clusters including right and left postcentral gyri, left parietal operculum, dorsal precuneus, left superior frontal gyrus/anterior cingulate cortex, and posterior cingulate cortex/ventral precuneus. For the contrast moderate-fear vs neutral, patients showed greater differential activation than controls in the right and left posterolateral cerebellum. Activation patterns in the precuneus and posterior cingulate cortex were negatively associated with pain-related fear, but no other correlations were observed. Together, the findings suggest that when conceptualizing neck-specific movements associated with pain, people with chronic whiplash-associated disorders may predict-and potentially amplify-their sensory and affective consequences and therewith trigger dysfunctional affective and/or behavioral responses. Herewith, we provide new insights into the neural mechanisms underlying chronic pain in people with whiplash-associated disorders, pointing towards a complex interplay between cognitive/affective and sensorimotor circuitry.

Is there any benefit of adding a central nervous system-focused intervention to a manual therapy and home stretching program for people with frozen shoulder? A randomized controlled trial.

BACKGROUND: Frozen shoulder (FS) is a highly disabling pathology of poorly understood etiology, which is characterized by the presence of intense pain and progressive loss of range of motion. The aim of this study was to evaluate the effect of adding a central nervous system (CNS)-focused approach to a manual therapy and home stretching program in people with FS. METHODS: A total of 34 patients with a diagnosis of primary FS were randomly allocated to receive a 12-week manual therapy and home stretching program or manual therapy and home stretching program plus a CNS-focused approach including graded motor imagery and sensory discrimination training. The Shoulder Pain and Disability Index score, self-perceived shoulder pain (visual analog scale score), shoulder range of motion, and the Patient-Specific Functional Scale score were measured at baseline, after a 2-week washout period just before starting treatment, after treatment, and at 3 months' follow-up. RESULTS: No significant between-group differences in any outcome were found either after treatment or at 3 months' follow-up. CONCLUSION: A CNS-focused approach provided no additional benefit to a manual therapy and home stretching program in terms of shoulder pain and function in people with FS.

Clinical Effectiveness of Dry Needling in Patients with Musculoskeletal Pain-An Umbrella Review.

The number of systematic reviews (SR) summarizing the literature regarding the clinical effects of Dry Needling (DN) has increased rapidly. Yet, rigorous evidence about the clinical effectiveness of this technique is still lacking. The aim of this umbrella review is to summarize the evidence about the clinical effects of trigger point DN on musculoskeletal disorders across all body regions. PubMed, Web of Science and Embase were searched to identify SRs examining the effect of DN (as a stand-alone intervention or combined with another treatment modality) compared to sham/no intervention or a physical therapy (PT) intervention with at least one clinical outcome in the domain of pain or physical functioning. Risk of bias (RoB) was assessed with the AMSTAR-2 tool. Quantification of the overlap in primary studies was calculated using the corrected covered area (CCA). The electronic search yielded 2286 results, of which 36 SRs were included in this review. Overall, DN is superior to sham/no intervention and equally effective to other interventions for pain reduction at short-term regardless of the body region. Some SRs favored wet needling (WN) over DN for short-term pain reductions. Results on physical functioning outcomes were contradictory across body regions. Limited data is available for mid- and long-term effects. DN has a short-term analgesic effect in all body regions and may be of additional value to the interventions that are used to date in clinical practice. Several studies have shown an additional treatment effect when combining DN to physiotherapeutic interventions compared to these interventions in isolation. There is a substantial need for the standardization of DN protocols to address the problem of heterogeneity and to strengthen the current evidence.

Prophylaxis and hemophilia care in LATAM: Baring it all-Highlights from the CLAHT 2021 symposium.

A large group of countries constitute Latin American (LATAM) countries, where hemophilia care is as varied as the landscape of this region. To better understand the care provided to persons with bleeding disorders, especially hemophilia, a symposium was organized as part of the CLAHT Congress 2021 in Colombia to highlight the issues of hemophilia care and challenges faced by persons with hemophilia in four LATAM countries, Colombia, Peru, Argentina, and Mexico. A summary of the symposium is provided. Four clinicians highlighted the issues in their own country, the status, and the path forward to bring the standard of care to the international level in each of these countries. The geography of the country, the health infrastructure, and the resources available are obstacles in these countries to provide state-of-the-art care to the bleeding disorder community. However, depending on the country, its infrastructure and the resources available, progress is being made to upend the care provided. Indeed, the care of persons with hemophilia has been greatly improved, including personalized prophylaxis. The information summarized here first emphasizes how the geography of a country and the different healthcare infrastructures play a major role in how care is offered. It also provides a path for other countries to evaluate these issues in their own realities. In parallel, these data provide hope to many developing countries; despite obstacles, strides can be made in the care of the bleeding disorder community.

Leucemia y Covid-19 (Leucovid-19): efecto de la pandemia sobre el diagnóstico de leucemia aguda en la Ciudad de México previo a Ómicron.

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How do psychologically based interventions for chronic musculoskeletal pain work? A systematic review and meta-analysis of specific moderators and mediators of treatment.

Psychologically based interventions aim to improve pain-related functioning by targeting pain-related fears, cognitions and behaviors. Mediation and moderation analyses permit further examination of the effect of treatment on an outcome. This systematic review and meta-analysis aims to synthetize the evidence of specific mediators and moderators (i.e., treatment targets) of psychologically based treatment effects on pain and disability. A total of 28 mediation and 11 moderation analyses were included. Thirteen mediation studies were included in a meta-analysis, and the rest was narratively synthetized. Reductions in pain-related fear (indirect effect [IE]: -0.07; 95% confidence interval [CI]: -0.11, -0.04) and catastrophizing (IE: -0.07; 95%CI: -0.14, -0.00), as well as increases in self-efficacy (IE: -0.07; 95%CI: -0.11, -0.04), mediated effects of cognitive behavioral therapy on disability but not on pain intensity, when compared to control treatments. Enhancing pain acceptance (IE: -0.17; 95%CI: -0.31, -0.03) and psychological flexibility (IE: -0.30; 95%CI: -0.41, -0.18) mediated acceptance and commitment therapy effects on disability. The narrative synthesis showed conflicting evidence, which did not support a robust moderated effect for any of the examined constructs. Overall, the methodological quality regarding mediation was low, and some key pitfalls are highlighted alongside recommendations to provide a platform for future research.

An abdominal phantom with anthropomorphic organ motion and multimodal imaging contrast for MR-guided radiotherapy.

Purpose. Improvements in image-guided radiotherapy (IGRT) enable accurate and precise treatment of moving tumors in the abdomen while simultaneously sparing healthy tissue. However, the lack of validation tools for newly developed MR-guided radiotherapy hybrid devices such as the MR-Linac is an open issue. This study presents a custom developed abdominal phantom with respiratory organ motion and multimodal imaging contrast to perform end-to-end tests for IGRT treatment planning scenarios.Methods. The abdominal phantom contains deformable and anatomically shaped liver and kidney models made of Ni-DTPA and KCl-doped agarose mixtures that can be reproducibly positioned within the phantom. Organ models are wrapped in foil to avoid ion exchange with the surrounding agarose and to provide stable T1 and T2 relaxation times as well as HU numbers. Breathing motion is realized by a diaphragm connected to an actuator that is hydraulically controlled via a programmable logic controller. With this system, artificial and patient-specific breathing patterns can be carried out. In 1.5 T magnetic resonance imaging (MRI), diaphragm, liver and kidney motion was measured and compared to the breathing motion of a healthy male volunteer for different breathing amplitudes including shallow, normal and deep breathing.Results. The constructed abdominal phantom demonstrated organ-equivalent intensity values in CT as well as in MRI. T1-weighted (T1w) and T2-weighted (T2w) relaxation times for 1.5 T and CT numbers were 552.9 ms, 48.2 ms and 48.8 HU (liver) as well as 950.42 ms, 79 ms and 28.2 HU (kidney), respectively. These values were stable for more than six months. Extracted breathing motion from a healthy volunteer revealed a liver to diaphragm motion ratio (LDMR) of 64.4% and a kidney to diaphragm motion ratio (KDMR) of 30.7%. Well-comparable values were obtained for the phantom (LDMR: 65.5%, KDMR: 27.5%).Conclusions. The abdominal phantom demonstrated anthropomorphic T1 and T2 relaxation times as well as HU numbers and physiological motion pattern in MRI and CT. This allows for wide use in the validation of IGRT including MRgRT.

Overexpression of BCL2, BCL6, VEGFR1 and TWIST1 in Circulating Tumor Cells Derived from Patients with DLBCL Decreases Event-Free Survival.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoid neoplasm and is the most common subtype of non-Hodgkin lymphoma in adults. More than half of patients with DLBCL can achieve remission with standard R-CHOP regimes; however, approximately 30-40% of patients are still failing this standard therapy, which remains as an important cause of progression and mortality of this disease. It is necessary to have diagnostic and monitoring tools that allow us to improve the accuracy of prognosis in these patients. Circulating tumor cells (CTCs) identification through molecular biomarkers is one of the novel strategies that have been used in other types of cancer, and we aim to use this tool to analyze the potential role in DLBCL. Patients and Methods: We analyzed 138 blood samples of patients with DLBCL, of which CTCs were isolated by density gradient for subsequent detection and quantitation of molecular biomarkers using RT-qPCR with TaqMan probes. Survival analysis was performed using Kaplan-Meier curves. Results: We found overexpression of ABCB1, αSMA, BCL2, BCL6 and VEGFR1 genes, as well as the presence of CK19, EpCAM, KI67, MAGE-A4, SNAIL and TWIST1 genes. CK19 and EpCAM expression were associated with a minor OS (85.7% vs 98.1%, p = 0.002). The overexpression of BCL2, BCL6, VEGFR1 and TWIST1 was related to a minor EFS (p = 0.001). Conclusion: This study showed that in liquid biopsies analyzed, the presence of CTCs can be confirmed through molecular biomarkers, and it has an impact on OS and EFs, making this detection useful in the follow-up and prognosis of patients with DLBCL.

Temporal changes in pain processing after whiplash injury, based on Quantitative Sensory Testing: A systematic review.

BACKGROUND AND OBJECTIVE: After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST). DATABASES AND DATA TREATMENT: This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. RESULTS: The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%-78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients. CONCLUSIONS: Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification. SIGNIFICANCE: Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.

El uso del lisímetro de pesada en clavel (Dianthus caryophyllus L.) genera ahorro en fertirriego / The use of the weighing lysimeter in carnation (Dianthus caryophyllus L.) generates saving in fertigation

RESUMEN El exceso o déficit en el volumen de fertirriego genera desbalances nutricionales, en razón a que influyen en el pH y la CE, afectando el desempeño de las plantas. Además, el descontrol del volumen de fertirriego puede causar excesos de lixiviados con efectos perjudiciales en el medioambiente. La fertirrigación en la producción de clavel en la Sabana de Bogotá, se hace de forma empiríca, por tanto, es indispensable ajustar el volumen de fertirriego a las necesidades del cultivo, para evitar los problemas mencionados. Por esta razón, se evaluó el efecto del control del volumen de fertirriego con lisímetro de peasada, en comparación con el manejo del fertirriego tradicional, en el desempeño de las plantas de miniclavel, sembradas en sutrato, en condiciones de invernadero. Para la evaluación, se realizó un diseño experimental en bloques completos al azar, con los tratamientos de sistema de cultivo con lisímetro (CL) y sistema de cultivo con fertirriego tradicional sin lisímetro (SL). Las variables evaluadas fueron volumen de riego, contenido nutricional de planta completa en cinco estadios fenológicos, pH y nutrientes mayores y secundarios (Ca-Mg), en el sustrato y en la solución drenada. El CL genera un ahorro en el volumen de fertirriego en comparación con el SL. Se encontraron diferencias en el continuo planta - sustrato - lixiviado, en N, K, Mg, así como en el pH del sustrato. El CL fue más eficiente, al generar mayor acumulación de masa seca, con el uso de menos agua y nutrientes, sin afectar el rendimiento, ni la calidad.

ABSTRACT The amount of fertigation excess or deficit generates nutritional unbalances given it affects pH, CE, and the nutrients balance influencing the plant development performance. In addition, the uncontrolled fertigation volume can cause an excess of leachates with detrimental effects on the environment. The Fertigation in carnation production in the Bogotá savanna is done empirically, therefore, it is essential to adjust the fertigation volume to the needs of the crop to avoid the mentioned problems. For this reason, the effect of the control of the fertigation volume with weighting lysimeters was evaluated in comparison with the management of traditional fertigation in the performance of the spray carnation plants sown in substrate under greenhouse conditions. For the evaluation, an experimental design was carried out in complete randomized blocks with a lysimeter crop system (LCS) and a traditional crop system without a lysimeter (WLS) as treatments. Irrigation volume, whole plant nutritional content in five phenological stages, pH, primary and secondary (Ca - Mg) nutrients in the substrate, and drainage solution were the variables evaluated. The LCS generates saving in the use of fertigation compared with WLS. Differences were found in the continuum plant - substrate - leached in N, K, Mg, as well as in the pH of the substrate. The LCS treatment was more efficient by generating greater dry mass accumulation, with the use of less water and nutrients without affecting the yield or quality.